Disclaimer
This information collection is a core HTA, i.e. an extensive analysis of one or more health technologies using all nine domains of the HTA Core Model. The core HTA is intended to be used as an information base for local (e.g. national or regional) HTAs.

Fecal Immunochemical Test (FIT ) versus guaiac-based fecal occult blood test (FOBT) for colorectal cancer screening

Fecal Immunochemical Test (FIT) for colorectal cancer screening compared to CRC screening with Guaiac –based fecal occult blood test (gFOBT) in the screening of Adenomas, as non-malignant precursor lesions of ColoRectal Cancer (CRC). in healthy and/or asymptomatic adults and elderly Any adult over 50 years old, both men and women, with average risk of CRC.

(See detailed scope below)

HTA Core Model Application for Screening Technologies 1.0
Core HTA
Published
Tom Jefferson (Agenas - Italy), Marina Cerbo (Agenas - Italy), Nicola Vicari (Agenas - Italy)
Mirjana Huic (AAZ), Agnes Männik (UTA - Estonia), Jesus Gonzalez (ISCIII - Spain), Ingrid Rosian (GÖG - Austria), Gottfried Endel (HVB - Austria), Valentina Rupel (IER - Slovenia), Alessandra Lo Scalzo (Agenas - Italy), Ingrid Wilbacher (HVB - Austria)
Agenas - Agenzia nazionale per i servizi sanitari regionali
AAZ (Croatia), AETSA (Spain), A. Gemelli (Italy), Avalia-t (Spain), CEIS (Italy), CEM (Luxembourg), GÖG (Austria), HAS (France), HVB (Austria), IER (Slovenia), ISCIII (Spain), Laziosanità (Italy), NCPHA (Bulgaria), NIPH (Slovenia), NSPH (Greece), NSPH MD (Romania), Osteba (Spain), Regione Veneto (Italy), SBU (Sweden), SNHTA (Switzerland), THL (Finland), UTA (Estonia).
5.4.2013 13.07.00
31.7.2014 9.21.00
Jefferson T, Cerbo M, Vicari N [eds.]. Fecal Immunochemical Test (FIT ) versus guaiac-based fecal occult blood test (FOBT) for colorectal cancer screening [Core HTA], Agenas - Agenzia nazionale per i servizi sanitari regionali; 2014. [cited 14 November 2019]. Available from: http://meka.thl.fi/ViewCover.aspx?id=206

Fecal Immunochemical Test (FIT ) versus guaiac-based fecal occult blood test (FOBT) for colorectal cancer screening

Collection summary

Background

Colorectal cancers (CRCs) arise mostly from previously begin adenomas and have effective treatment if diagnosed early in their evolution. It is for these reasons that they are amenable to screening. Screening can be done via three approaches: imaging, endoscopy and stool-based identification. Two of the techniques used in stool-based based identification are the object of this core HTA, collectively knows as Fecal occult blood tests (FOBT): (guaiac, so-called gFOBT and immunochemical testing, so called FIT, also known as Immunochemical Faecal Occult Blood Test (iFOBTs).

CRC is the 3rd most common cancer worldwide, and the second most frequent in developed countries with an estimated 1,234,000 cases worldwide in 2008. There are large variations between regions. Incidence rates are higher in Australia/New Zealand (39.0 per 100,000), Western Europe (33.1 per 100,000) and Southern Europe (31.1 per 100,000) and lower in Western Africa (4.9 per 100,000), South-Central Asia (4.5 per 100,000) and Middle Africa (3.7 per 100,000) {6}. In 2008 an estimated 8% of total cancer-related deaths was caused by CRC. Incidence and mortality from CRC are higher in men that in women.

Currently screening practices vary considerably across Europe (see assessment element CUR 14),

Several different types and brands of FOB tests are available, with different performance characteristics.

gFOBT is the longest established of the two basic techniques, guaiac and immune based. There are several potential advantages and disavantages of gFOBT use. The advantages are mainly due to the cheapness, acceptability and long standing nature of the procedure. The disadvantages of gFOBT are its lack of automation, laboriousness and lack of specificity for human Haemoglobin, requiring a period of dietary preparation before testing.

FITs are a newer class of Faecal Occult Blood tests compared to gFOBTs and reputedly have improved test characteristics compared to gFOBT. iFOBTs have been used for population CRC screening in Japan since 1992. In the US, the first iFOBT (OC-Sensor) was approved by the FDA (Food and Drug Administration) since 2001. The aim of population-based screening for CRC is to reduce morbidity and mortality from CRC through both, prevention (by the removal of adenomas before they had a chance to become malignant, so CRC incidence is reduced) and earlier diagnosis of CRC (at early, curable stage).

A wide range of qualitative and quantitative FITs is presently available, with varying levels of sensitivity and specificity. They all use antibodies raised against human haemoglobin (Hb) to detect human blood present in faeces.

The aim of this core HTA was to compare the diagnostic and clinical performance of FITs with gFOBT for detection of CRC.

Results

Safety of the technology (SAF)

As FIT and gFOBT are non-invasive tests no direct harms are likely. Indirect harms can be caused by a wrong or delayed diagnosis or by harms related to subsequent colonoscopy (such as local trauma). The psychological impact of screening (including consequences of any false-positive and false-negative test results) and patient discomfort related to the procedures are the potential harms to be assessed as the overall number of adverse events depends on sensitivity and specificity of the  screening tests. False-positive results may cause anxiety and distress, overdiagnosis and overtreatment. The false-negative test results may delay the detection of illness and the start of treatment. Organisational factors affecting harms include false-positive test results from gFOBT with a lax dietary preparation and FIT samples should be kept in refrigerated. Personnel experience and dexterity is also a factor.

Harms colonoscopy are estimated at 5% of procedures whereas 68% of people who received a false positive experienced stress and 46% of those who received an invitation to screening were worried and 15% very worried.

Effectiveness of the technology (EFF)

Our searches were unable to identify a direct comparison of the two techniques with meaningful cancer-specific outcomes such as CRC mortality within screening programmes.

However on the basis of several single studies and systematic review FIT have higher detection rates than gFOBT for adenomas, at the expense of a drop in specificity. We concluded that Overall, FIT performance is superior to the standard gFOBT for the detection of CRC and advanced adenomas in a population based screening setting.  

Costs, economic evaluation of the technology (ECO)

FIT lacks evidence of its effect on mortality when used in a screening programme, but both tests are more cost-effective than no screening. Cost-effectiveness models tend to suggest FIT has more favourable ICERs than gFOBT but its higher sensitivity means that there is a need for  higher capacity in undertaking diagnostic colonoscopies with an increased up-front resource use and cost associated with the increased number of colonoscopies.

Ethical aspects of the technology (ETH)

The tests are very similar, making ethical problems around choice less important. Overall there appears to be dominance of FIT over gFOBT and both dominate no screening. However in the absence of a direct clinical comparison the evidence base is unstable as shown by the different ICERs in ECO5. A full assessment should be carried out in context to define the costs and opportunity costs as well as the benefits of choice between the two types of test.

Organisational aspects of the technology (ORG)

CRC screening is carried out with significant variation across the EU in terms of organization and type of screening test. There partial or complete screening programmes in 19 of the 27 EU countries. Organised screening is considered better than opportunistic screening. In 2007, gFOBT was used as the only screening method in twelve countries: Bulgaria, Czech Republic, Finland, France, Hungary, Latvia, Portugal, Romania, Slovenia, Spain, Sweden, and United Kingdom. In six countries, two types of tests were used: FIT and FS in Italy, and gFOBT and colonoscopy in Austria, Cyprus, Germany, Greece, and Slovak Republic. FIT is being used in 6 European countries: Russia, Lithuania, Italy, Scotland, Spain and Slovenia.

National screening programmes use risk-based criteria to define who should receive screening invitations. The target population for a CRC screening programme includes all people eligible to attend screening on the basis of age and geographical area of residence. Altough there are variations, people who are between 50 and 75 are invited to be screened.

Screening programmes with FIT carry an investment penalty including equipment for screening, premises, office material for posting invitations and re-invitations, IT equipment and other office devices such as printers, and human resources including administrative and health personnel, investment in education of personnel and their training. Every country needs to assess their costs independently using cost-effectiveness analyses or other economic evaluation method. Investments that are needed for implementation of FIT are therefore country specific.

Social aspects of the technology (SOC)

We found good evidence that FIT has better compliance than gFOBT in screening. The reasons for this finding are unclear and under researched but may include socio-cultural factors and the need for dietary prepration for gFOBT.

Legal aspects of the technology (LEG)

Legals implications of detecting colorectal cancer include the necessity to provide Sufficient information and informed consent, the right of access to (best) health care once a presumptive diagnosis is made, freedom in taking part, protection of personal data, equal right of access according to need and in the case of regional inequalities, access abroad and the right to charge contributions to the cost of the programme.

Closing Remarks

The Core Model is not intended to provide a cookbook solution to all problems but to suggest a way in which information can be assembled and structured, and to facilitate its local adaptation. The information is assembled around the nine domains, each with several result cards in which questions and possible answers are reported.

The reasons for having a standardised but flexible content and layout are rooted in the way HTA is conducted in the EU and in the philosophy of the first EUnetHTA Joint Action (JA1) production experiment.

HTA is a complex multidisciplinary activity addressing a very complex reality – that of healthcare. Uniformly standardised evidence-based methods of conducting assessments for each domain do not exist (Corio M, Paone S, Ferroni E, Meier H, Jefferson TO, Cerbo M. Agenas – Systematic review of the methodological instruments used in Health Technology Assessment. Rome, July 2011.)). There are sometimes variations across and within Member States in how things are done and which aspects of the evaluation are privileged. This is especially so for the “softer” domains such as the ethical and social domains.

Collection methodology

Objective

To produce a Core Health Technology Assessment (HTA) comparing the performance of fecal occult blood tests (FOBT - guaiac, so-called gFOBT and immunochemical testing, so called FIT, also known as Immunochemical Faecal Occult Blood Test - iFOBT) for colorectal cancers (CRCs) based on the EUnetHTA Core Model.

Methods

The work was based on the HTA Core Model on screening technologies, which was developed during the EUnetHTA Joint Action 1 (JA1).

The first phase was the selection of the technology to be assessed using the Core Model; this phase was carried out through a three-step process that is described in our MSP.

Then there was the check of Partners’ availability to assume responsibility, as an institution, to take the lead in one of the nine evaluation domains. At the same time, the nine domain teams were built-up in accordance with partners’ preferences and some general guidelines (i.e.: “each WP4/B Associated partner AP should be involved in at least one domain, indicating its interest for at least one domain”)

Finally the specific work plan was shared, according with the general WP4 3-year work plan and objectives. This specific work plan included the phases scheduled in the “HTA Core Model Handbook” (Production of Core HTAs and structured HTA information).

An editorial team was set up for discussion and major decisions on basic principles and solutions related to the content of core HTA. The editorial team was chaired by Tom Jefferson (Agenas) and composed of all the primary investigators of the domains.

To allow collaboration between partners a draft protocol for Core Model use was agreed by the researchers involved. The research questions for each of the nine domains of the Core Model were formulated and the corresponding relevant assessment elements (AEs) were selected.

The research strategy was carried out by Agenas with input from the other partners.

Evidence from published and manufacturer sources was identified, retrieved, assessed, and included according to pre-specified criteria, and summarised to answer each AE. Work was carried with domain assessments being made by a single agency and by different investigators from different agencies, in a mixed organisational model.

Introduction to collection

This brief document provides background information on the preparation and development of the Core HTA on CRC detection. The core HTA document was produced during the course of the second EUnetHTA Joint Action (JA2) 2012-2015.

The idea behind EUnetHTA’s Core Model is to provide a framework for structuring relevant HTA information while at the same time facilitating local use and adaptation of the information or guiding its production.

The Model is based on nine dimensions or “domains” of evaluation:

  1. Health Problem and Current Use of the Technology (CUR)
  2. Description and technical characteristics of technology (TEC)
  3. Safety (SAF)
  4. Effectiveness (EFF)
  5. Costs and economic evaluation (ECO)
  6. Ethical analysis (ETH)
  7. Organisational aspects (ORG)
  8. Social aspects (SOC)
  9. Legal aspects  (LEG)

The Core HTA was sent to the Stakeholder Advisory Group (SAG) for feedback before the final Public Consultation and the comments received where included where applicable.

Scope

TechnologyFecal Immunochemical Test (FIT) for colorectal cancer screening
Description

FITs use an antibody (immunoglobulin) specific to human globin, the protein component of haemoglobin, to detect fecal occult blood. Immunochemical tests have improved test characteristics compared to conventional guaiac-based tests for fecal occult blood. FIT should not be subject to interference from dietary blood and it is more specific to bleeding from the distal gastrointestinal tract. They could be analytically and clinically more sensitive and specific, Their measurement can be automated and the user can adjust the concentration at which a positive result is reported. A wide range of qualitative and quantitative tests is presently available, with varying levels of sensitivity and specificity (like Hem-SP/MagStream H, Fujirebio Inc. Japan ; OC-Sensor, Eiken Chemical Co., Tokyo, Japan;    FOB Gold, Medinostics Products Supplier; Sentinel Diagnostics SpA, Milan, Italy).

Intended use of the technologyScreening

CRC screening with faecal inmunochemical test (FIT) for detection of occult blood in the stool associated with colorectal lesions (adenomas and CRC).

The use of the test is considered under conditions of population based colorectal cancer screening, in the context of organised cancer screening programmes as recommended by the EU. Early detection and treatment of colorectal lesions before they become symptomatic has the potential to improve control of the disease, reducing morbidity and mortality associated to CRC. Early treatment of invasive lesions can be generally less detrimental for quality of life. The endoscopic removal of pre-malignant lesions also reduces the incidence of CRC by stopping the progression to cancer. Colorectal cancers and adenomatous polyps bleed has providing fecal blood haemoglobin as the biomarker of choice for current screening programmes. Stool samples could be periodically taken and analyzed for the presence of occult blood, as an early sign of colorectal lesions (adenoma or CRC).

Target condition
Adenomas, as non-malignant precursor lesions of ColoRectal Cancer (CRC).
Target condition description

CRC is the third most common in incidence and the fourth most common cause of cancer death worldwide. CRC is particularly suitable for screening. The disease is believed to develop in a vast majority of cases from non-malignant precursor lesions called adenomas. Adenomas can occur anywhere in the colorectum after a series of mutations that cause neoplasia of the epithelium. At some time , the adenoma may invade the submucosa and become malignant. Initially, this malignant cancer is not diagnosed and does not give symptoms  (preclinical phase). It can progress from localised (stage I) to metastasised (stage IV) cancer, until it causes symptoms and is diagnosed. Only 5–6% of the population actually develop CRC. The average duration of the development of an adenoma to CRC is estimated to be  at least 10 years. This long latent phase provides a window of opportunity for early detection of the disease.

Target population

Target population sex: Any. Target population age: adults and elderly. Target population group: Healthy and/or asymptomatic people.

Target population description

Adults, average risk of CRC, aged 50 years or over.

The best age range for offering gFOBT or FIT screening has not been investigated in trials. Circumstantial evidence suggests that mortality reduction from gFOBT is similar in different age ranges between 45 and 80 years .The age range for a national screening programme should at least include people aged 60 to 64 years in which CRC incidence and mortality are high and life-expectancy is still considerable. Only the FOBT for men and women aged 50–74 years has been recommended todate by the EU (Council Recommendation and the European guidelines for quality assurance in CRC screening and diagnosis).

Members of families with hereditary syndromes, previous diagnosis of CRC or pre-malignant lesions should follow specific surveillance protocols and are not included in the target population

ComparisonCRC screening with Guaiac –based fecal occult blood test (gFOBT)
Description

CRC screening with Guaiac–based fecal occult blood test (gFOBT)

The guaiac-based FOBT is still a commonly used method for detecting blood in faeces. To detect hemoglobin the test uses guaiac gum and its efficacy as a colorectal cancer screening test has been analyzed in several randomised controlled trials. The test detects the haem component of haemoglobin, which is identical across human and animal species and is chemically robust and only partially degraded during its passage through the gastrointestinal tract. gFOBTs cannot distinguish between human blood and blood residues from the diet.

Many guaiac-based tests are currently on the market (like Coloscreen, Helena Laboratories,Texas,USA; Hema-screen Immunostics Inc.; Hemoccult, Beckman Coulter Inc.; Hemoccult SENSA, Beckman Coulter Inc.; MonoHaem, Chemicon Europe Ltd; Hema-Check, Siemens PLC; HemaWipe, Medtek Diagnostics LLC)

The use of the test is considered under conditions of population based colorectal cancer screening, in the context of organised cancer screening programmes as recommended by the EU. Population-based programmes have been rolled out nationwide in several European countries. Many member states  haveestablished nationwide non-population-based programmes. Some states are planning or piloting a nationwide population-based programme. These have  adopted only FOBT, some only FIT, some a mix between FOBT and endoscopy, or only colonoscopy.

Outcomes

CUR and TEC

  • Health problems (target condition)
  • Epidemiology
  • Burden of disease
  • Target population
  • Current management of the condition
  • Features of the technology
  • Life-Cycle
  • Regulatory status
  • Utilization
  • Investments and tools required to use the technology
  • Training and information needed to use the technology

SAF

  • Colonoscopy probability of perforation
  • Colonoscopy with polypectomy probability of perforation
  • Colonoscopy probability of death following perforation
  • Probability of bleeding following colonoscopy
  • Psychological harms from false-negatives and false-positives (and generally from participating in screening program)

EFF

  • Test (FIT and gFOBT) sensitivity for adenomas
  • Test (FIT and gFOBT) sensitivity for cancer
  • Test (FIT and gFOBT) specificity for adenomas
  • Test (FIT and gFOBT) specificity for cancer 
  • Adenoma incidence (detection rates)
  • Rectal cancer incidence (detection rates)
  • Colon cancer incidence (detection rates)
  • CRC incidence (detection rates)
  • Stage distribution of detected cancers
  • Rectal cancer specific mortality
  • CRC specific mortality
  • Overall mortality
  • Life years saved

ECO:

  • Model/template for  national pilots  to assess the costs and benefits of the two alternative  technologies FIT and gFOBT  and also no-programmed-screening
  • Systematic literature search of   available models and/or economic  evaluation for screening colorectal cancer with FIT and gFOBT and no screening programme
  • Resource Utilization: Publicly funded health care payer costs (screening tests, further examinations e.g. labor, colonoscopy  and treatments and administration and organisation costs of screening programme) for FIT and gFOBT (in cooperation with ORG)
  • Cost per Case detected (average, marginal, incremental) =  intermediate outcome – optional, not decided yet (relevant for deciding how often a test should be carried out and what are the incremental costs for a “new” detected case
  • Indirect Costs: not for the Core modell (should be decided later on)
  • Test accuracy: from SAF
  • Cost effectiveness analysis: HRQoL measures (both generic and context specific) (EFF and SAF for help, own Lit.research), ICER

 ORG:

  • Responsiveness of target population to invitation
  • Invitation-reminder system
  • Competence of human resources – health professionals
  • Investments needed (material,equipment)
  • Costs of using both tests (FIT, gFOBT)
  • Timeliness of results and future phases
  • Use of tools for process monitoring (completed check lists)
  • Model for Budget Impact Analysis from perspective of the payer

SOC

  • Compliance with the tests (FIT, gFOBT)
  • Anxiety and any psychological effects of using  one test or another
  • Information, counseling, communication (quality of) for the use of tests
  • Satisfaction  
  • Quality of life
  • Equity of access

LEG

  • Information as baseline for an informed consent
  • Harms or inequities that can be taken to court

Health Problem and Current Use of the Technology

Authors: Mirjana Huic, Eleftheria Karampli, Silvia Florescu, Cipriana Mihaescu-Pintia

Summary

Aim To give broad overview on the health problem of colorectal carcinoma (CRC), the screening population and the current use of different CRC screening methods in Europe, as well as FIT use, an alternative name for Immunochemical faecal occult bleeding test (iFOBT), a class of occult blood tests which represents one out of few different screening options CRC.

Methods The Project scope is applied in this Domain. Results cards are covered by evidence gathered from basic literature search, hand searched literature, manufacturers web sites, company brochures and information for use, and survey (questionnaire) results. No quality assessment tool was used, but multiple sources were used in order to validate individual, possibly biased, sources. Descriptive analysis was performed on different information sources. The assessment elements questions are answered by cooperation of Domain investigators.

Results Colorectal cancer (CRC) is the 3rd most common cancer worldwide, and the second most frequent in developed countries. Most colon cancers arise from non-malignant adenomas in form of adenomatous polyps. Due such natural course, CRC is particularly suitable for screening. The aim of population-based screening for CRC is to reduce morbidity and mortality from CRC through both prevention (by the removal of adenomas before they become malignant) and earlier diagnosis of CRC (at early, curable stage). In developed countries, approximately, 40.50% of the population develop one or more adenomas in a lifetime, but the majority of these adenomas will never develop into CRC. Only 5.6% of the population actually develop CRC. The average duration of the development of an adenoma to CRC is unobserved, but is estimated to take at least 10 years. Focusing on Europe, in 2008, CRC accounted for 12.4% of deaths caused by malignancy in European countries (11.5% and 13.5% of total cancer deaths in men and women respectively). In Europe, an increasing trend in average incidence of CRC has been observed in recent years, and in the future, the number of new cases and deaths related to CRC are expected to increase. In specific, the International Agency on Research for Cancer (IARC) estimates the number of new CRC cases in Europe (in all ages) to rise to 502,000 in 2020, whereas the annual deaths from CRC in Europe are expected to rise to 248,000.

Target population for CRC screening includes asymptomatic people at average risk, of both genders, age 50-74. There are various methods available for colorectal cancer screening. They can be broadly divided into endoscopic and radiologic methods (for example colonoscopy) and stool-based tests (guaiac-based or immunochemical Faecal occult blood tests - FOBTs, Faecal DNA testing). Routine screening of stool for occult blood may facilitate early detection. Guaiac-based Faecal Occult Blood (gFOBT) tests are those mostly studied in RCTs as screening test for CRC and are an established screening strategy for CRC. Several large randomized studies have demonstrated a reduction in cancer-related mortality. FIT (Faecal Immunochemical test) is an alternative name for Immunochemical Faecal Occult Blood Test (iFOBT), a class of occult blood tests which represents one out of few different screening options for colorectal cancer (CRC). A number of countries have organised CRC screening programmes utilising different strategies. FOB testing is a widely implemented strategy, however there are differences in the type of tests used (gFOBT or iFOBT). From the information provided via the EUnetHTA member survey, use of immunochemical testing (FIT) was reported in 5 out of 11 responded (i. e. Austria, Russia, Luxembourg, Lithuania, Italy, Scotland, Spain, Romania, France, Croatia and Slovenia) European countries. In specific, FIT is used in the Regions of Veneto and Lazio in Italy, Lithuania, Russia, Slovenia and Spain. In Austria, FIT is used only in one province (Burgenland). According to data (May 2008) from the International Cancer Screening Network, CRC screening programmes utilising immunochemical techniques had been implemented in Hungary (2 pilots) and Italy. In Italy, the majority of programmes use FIT, a limited number offer flexible sigmoidoscopy (FS) once in a lifetime and FIT for non-responders to FS. Participation rates in various CRC screening programmes (pilot programmes, established programmes) in Europe and abroad broadly varies from 14.4%-63.8%. Various technologies are available for the diagnosis of adenomas and CRC. Colonoscopy is the gold standard and allows biopsy for histology.

Several different types and brands of FOB tests are available, with different performance characteristics. Potential advantages of gFOBT, as main comparator in this Core HTA, are: the collection card and reagent are cheap, the card based collection system is easy to pack using automated machinery and easy to send by post, easy to print patients details on the cards, the samples are considered to be stable on the cards for up to 21 days, the system has been validated in numerous RCTs, has been implemented in a number of bowel cancer screening programmes and work successfully. Disadvantages of gFOBT are: testing is not automated, test is labour intensive and involves subjective visual reading, the participants is required to prove samples from three separate bowel motions, it is not specific for human Hb, it is not possible to adjust the cut-off Hb concentration of the test.

According the EU Guideline 2010, "iFOBT have improved test characteristics than gFOBT, and they are currently the test of choice for population CRC screening. In different settings, individual device characteristics like ease of use by participant and laboratory, suitability for transport, sampling reproducibility and sample stability are important and should be all taken into account when selecting the iFOBT most appropriate for CRC screening programme (Level of evidence II, Grade of recommendation A). Adoption of test device and the selection of a cut-off concentration should follow a local pilot study to ensure that chosen test, test algorithm and transport arrangements work together to provide a positivity rate that is clinically, logistically and financially acceptable (Level of evidence VI, Grade of recommendation A). Maximum period between collection and analysis is significantly shorter  than for gFOBT (14-21 days), and screening programmes should adopt the conditions and period of storage described in manufacturer’s Instructions for use and should be appropriate for local conditions which might expose samples to high temperatures for long period of time (Level of evidence III, Grade of recommendation A). Despite the fact that dietary constituents present potential interference in gFOBT, dietary restriction has not been demonstrated to significantly increase screening specificity and risks reducing participation rate. The potential for dietary interference is significantly less for iFOBT. Some drugs which could cause GI bleeding like aspirin, NSAIDs and anticoagulants present potential interference in gFOBT and iFOBT, drug restriction is not recommended for population screening programmes using either gFOBT or iFOBT.“

The most clinically and cost-effective CRC screening method still should be determine in additional comparative effectiveness research. When making decision between different FOB tests (gFOBT or FIT) should be used for CRC screening, their analytical performance should be keep in mind as well as compliance and general acceptance of the test by the public.

Introduction

Colorectal cancer (CRC) is the 3rd most common cancer worldwide, and the second most frequent in developed countries. In the US, CRC accounts for 10% of cancer-related deaths; focusing on Europe, in 2008, CRC accounted for 12.4% of deaths caused by malignancy in European countries (11.5% and 13.5% of total cancer deaths in men and women respectively); incidence increases above age 50, the average age at diagnosis is 60-65 years. Different factors could increase or decrease risk for colorectal cancer. Factor which increased risk for CRC are: environmental factors (prevalence is increased in developed countries, urban areas); advantaged socioeconomic groups; hypercholesterolemia; coronary artery diseases; low-fiber, high-animal-fat diets; obesity; smoking; acromegaly; sugar consumption; family history (risk is increased in first-degree relatives of patients, families with increased prevalence of cancer, patients with breast or gynecologic cancer, familial polyposis syndromes);>10-year history of ulcerative colitis or Crohn's colitis;>15-year history of uretherosygmoidostomy. Risk is decreased with long term dietary calcium supplementation, vegetable, garlic, exercise, daily aspirin ingestion (after 5 years daily aspirin there is a 35% reduction in all GI cancers) and other NSAIDs.

Most colon cancers arise from non-malignant adenomas in form of adenomatous polyps. Due such naturale course, CRC is particularly suitable for screening.

The aim of population-based screening for CRC is to reduce morbidity and mortality from CRC through both prevention (by the removal of adenomas before they become malignant) and earlier diagnosis of CRC (at early, curable stage). Different screening tests for CRC are available, classified according to three categories:

 

Stool-based techniques: Fecal occult blood test (FOBT) (either guaiac, so called gFOBT and immunochemical, so called FIT); Fecal DNA testing.   Endoscopic techniques: Optical colonoscopy; Flexible sigmoidoscopy (FS).   Imaging techniques: Virtual colonoscopy techniques using: a) Computed tomographic colonography (CT colonography), b) Magnetic resonance colonography (MR colonography); Wireless capsule endoscopy; Double-contrast barium enema.   The aim of this Domain is to give broad overview on the health problem of colorectal carcinoma, the screening population and the current use of different CRC screening methods in Europe, as well as FIT, an alternative name for Immunochemical faecal occult bleeding test (iFOBT), a class of occult blood tests introduced in US market in 2001, which represents one out of few different screening options for colorectal cancer (CRC).

Methodology

Frame

The collection scope is used in this domain.

TechnologyFecal Immunochemical Test (FIT) for colorectal cancer screening
Description

FITs use an antibody (immunoglobulin) specific to human globin, the protein component of haemoglobin, to detect fecal occult blood. Immunochemical tests have improved test characteristics compared to conventional guaiac-based tests for fecal occult blood. FIT should not be subject to interference from dietary blood and it is more specific to bleeding from the distal gastrointestinal tract. They could be analytically and clinically more sensitive and specific, Their measurement can be automated and the user can adjust the concentration at which a positive result is reported. A wide range of qualitative and quantitative tests is presently available, with varying levels of sensitivity and specificity (like Hem-SP/MagStream H, Fujirebio Inc. Japan ; OC-Sensor, Eiken Chemical Co., Tokyo, Japan;    FOB Gold, Medinostics Products Supplier; Sentinel Diagnostics SpA, Milan, Italy).

Intended use of the technologyScreening

CRC screening with faecal inmunochemical test (FIT) for detection of occult blood in the stool associated with colorectal lesions (adenomas and CRC).

The use of the test is considered under conditions of population based colorectal cancer screening, in the context of organised cancer screening programmes as recommended by the EU. Early detection and treatment of colorectal lesions before they become symptomatic has the potential to improve control of the disease, reducing morbidity and mortality associated to CRC. Early treatment of invasive lesions can be generally less detrimental for quality of life. The endoscopic removal of pre-malignant lesions also reduces the incidence of CRC by stopping the progression to cancer. Colorectal cancers and adenomatous polyps bleed has providing fecal blood haemoglobin as the biomarker of choice for current screening programmes. Stool samples could be periodically taken and analyzed for the presence of occult blood, as an early sign of colorectal lesions (adenoma or CRC).

Target condition
Adenomas, as non-malignant precursor lesions of ColoRectal Cancer (CRC).
Target condition description

CRC is the third most common in incidence and the fourth most common cause of cancer death worldwide. CRC is particularly suitable for screening. The disease is believed to develop in a vast majority of cases from non-malignant precursor lesions called adenomas. Adenomas can occur anywhere in the colorectum after a series of mutations that cause neoplasia of the epithelium. At some time , the adenoma may invade the submucosa and become malignant. Initially, this malignant cancer is not diagnosed and does not give symptoms  (preclinical phase). It can progress from localised (stage I) to metastasised (stage IV) cancer, until it causes symptoms and is diagnosed. Only 5–6% of the population actually develop CRC. The average duration of the development of an adenoma to CRC is estimated to be  at least 10 years. This long latent phase provides a window of opportunity for early detection of the disease.

Target population

Target population sex: Any. Target population age: adults and elderly. Target population group: Healthy and/or asymptomatic people.

Target population description

Adults, average risk of CRC, aged 50 years or over.

The best age range for offering gFOBT or FIT screening has not been investigated in trials. Circumstantial evidence suggests that mortality reduction from gFOBT is similar in different age ranges between 45 and 80 years .The age range for a national screening programme should at least include people aged 60 to 64 years in which CRC incidence and mortality are high and life-expectancy is still considerable. Only the FOBT for men and women aged 50–74 years has been recommended todate by the EU (Council Recommendation and the European guidelines for quality assurance in CRC screening and diagnosis).

Members of families with hereditary syndromes, previous diagnosis of CRC or pre-malignant lesions should follow specific surveillance protocols and are not included in the target population

ComparisonCRC screening with Guaiac –based fecal occult blood test (gFOBT)
Description

CRC screening with Guaiac–based fecal occult blood test (gFOBT)

The guaiac-based FOBT is still a commonly used method for detecting blood in faeces. To detect hemoglobin the test uses guaiac gum and its efficacy as a colorectal cancer screening test has been analyzed in several randomised controlled trials. The test detects the haem component of haemoglobin, which is identical across human and animal species and is chemically robust and only partially degraded during its passage through the gastrointestinal tract. gFOBTs cannot distinguish between human blood and blood residues from the diet.

Many guaiac-based tests are currently on the market (like Coloscreen, Helena Laboratories,Texas,USA; Hema-screen Immunostics Inc.; Hemoccult, Beckman Coulter Inc.; Hemoccult SENSA, Beckman Coulter Inc.; MonoHaem, Chemicon Europe Ltd; Hema-Check, Siemens PLC; HemaWipe, Medtek Diagnostics LLC)

The use of the test is considered under conditions of population based colorectal cancer screening, in the context of organised cancer screening programmes as recommended by the EU. Population-based programmes have been rolled out nationwide in several European countries. Many member states  haveestablished nationwide non-population-based programmes. Some states are planning or piloting a nationwide population-based programme. These have  adopted only FOBT, some only FIT, some a mix between FOBT and endoscopy, or only colonoscopy.

Outcomes

CUR and TEC

  • Health problems (target condition)
  • Epidemiology
  • Burden of disease
  • Target population
  • Current management of the condition
  • Features of the technology
  • Life-Cycle
  • Regulatory status
  • Utilization
  • Investments and tools required to use the technology
  • Training and information needed to use the technology

SAF

  • Colonoscopy probability of perforation
  • Colonoscopy with polypectomy probability of perforation
  • Colonoscopy probability of death following perforation
  • Probability of bleeding following colonoscopy
  • Psychological harms from false-negatives and false-positives (and generally from participating in screening program)

EFF

  • Test (FIT and gFOBT) sensitivity for adenomas
  • Test (FIT and gFOBT) sensitivity for cancer
  • Test (FIT and gFOBT) specificity for adenomas
  • Test (FIT and gFOBT) specificity for cancer 
  • Adenoma incidence (detection rates)
  • Rectal cancer incidence (detection rates)
  • Colon cancer incidence (detection rates)
  • CRC incidence (detection rates)
  • Stage distribution of detected cancers
  • Rectal cancer specific mortality
  • CRC specific mortality
  • Overall mortality
  • Life years saved

ECO:

  • Model/template for  national pilots  to assess the costs and benefits of the two alternative  technologies FIT and gFOBT  and also no-programmed-screening
  • Systematic literature search of   available models and/or economic  evaluation for screening colorectal cancer with FIT and gFOBT and no screening programme
  • Resource Utilization: Publicly funded health care payer costs (screening tests, further examinations e.g. labor, colonoscopy  and treatments and administration and organisation costs of screening programme) for FIT and gFOBT (in cooperation with ORG)
  • Cost per Case detected (average, marginal, incremental) =  intermediate outcome – optional, not decided yet (relevant for deciding how often a test should be carried out and what are the incremental costs for a “new” detected case
  • Indirect Costs: not for the Core modell (should be decided later on)
  • Test accuracy: from SAF
  • Cost effectiveness analysis: HRQoL measures (both generic and context specific) (EFF and SAF for help, own Lit.research), ICER

 ORG:

  • Responsiveness of target population to invitation
  • Invitation-reminder system
  • Competence of human resources – health professionals
  • Investments needed (material,equipment)
  • Costs of using both tests (FIT, gFOBT)
  • Timeliness of results and future phases
  • Use of tools for process monitoring (completed check lists)
  • Model for Budget Impact Analysis from perspective of the payer

SOC

  • Compliance with the tests (FIT, gFOBT)
  • Anxiety and any psychological effects of using  one test or another
  • Information, counseling, communication (quality of) for the use of tests
  • Satisfaction  
  • Quality of life
  • Equity of access

LEG

  • Information as baseline for an informed consent
  • Harms or inequities that can be taken to court

Assessment elements

TopicIssue RelevantResearch questions or rationale for irrelevance
A0001Target ConditionWhich disease/health problem/potential health problem will the technology be used for?yesWhich disease/health problem/potential health problem will FIT be used for?
A0002Target ConditionWhat, if any, is the precise definition/ characterization of the target disease? Which diagnosis is given to the condition and according to which classification system (e.g. ICD-10)?yesWhat, if any, is the precise definition/ characterization of adenomas and/or colorectal carcinoma (CRC)? Which diagnosis is given to the condition and according to which classification system (e.g. ICD-10)?
A0003Target ConditionWhich are the known risk factors for acquiring the condition?yesWhich are the known risk factors for acquiring adenomas and/or CRC?
A0004Target ConditionWhat is the natural course of the condition?yesWhat is the natural course of CRC?
A0005Target ConditionWhat are the symptoms at different stages of the disease?yesWhat are the symptoms at different stages of adenomas and/or CRC?
A0006Target ConditionWhat is the burden of the condition?yesWhat is the burden of CRC?
A0009Target ConditionWhat aspects of the burden of disease are targeted by the technology?yesWhat aspects of the burden of CRC are targeted by CRC screening with FIT?
A0007Target PopulationWhat is the target population of the technology?yesWhat is the target population for colorectal carcinoma screening with FIT?
A0023Target PopulationHow many people belong to the target population?yesHow many people belong to the target population in Europe?
A0011UtilisationHow much is the technology being used?yesWhich countries use FIT for CRC screening?
Which percentage of target population is accually screened in countries with CRC screening program with FIT?
A0012UtilisationWhat kind of variations in use are there across countries/regions/settings?yesWhat kind of variations in use of CRC screening methods are there across countries/regions/settings?
A0013Current Management of the ConditionHow is the disease/health condition currently diagnosed or screened?yesHow are adenomas/CRC currently diagnosed?
How are adenomas/CRC currently screened?
A0014Current Management of the ConditionHow should the condition be diagnosed or screened according to published algorithms/guidelines?yesHow should adenomas/CRC be diagnosed or screened according to published algorithms/guidelines?
A0015Current Management of the ConditionHow is the condition currently managed?yesHow are adenomas/CRC currently managed?
A0016Current Management of the ConditionHow should the condition be managed according to published algorithms/guidelines?yesHow should adenomas/CRC be managed according to published algorithms/guidelines?
A0017Current Management of the ConditionWhat are the differences in the management for different stages of disease?yesWhat are the differences in the management for different stages of CRC?
A0018Current Management of the ConditionWhat are the other evidence-based alternatives to the current technology?yesWhat are the other evidence-based alternatives to CRC screening with FIT?
What are the technical characteristics and analytical validity of guaiac-based fecal occult blood test (FOBT), as main CRC screening comparator in this assessment?
A0019Life-CycleIn which phase is the development of the technology?yesIn which phase is the development of FIT?
A0020Regulatory StatusWhich market authorization status has the technology in other countries, or international authorities?yesWhich market authorization status (CE mark) has FIT in other countries, or international authorities?
A0021Regulatory StatusWhat is the reimbursement status of the technology across countries?yesWhat is the reimbursement status of CRC screening with FIT across countries?

Methodology description

Domain frame

The Project scope is applied in this domain.

 

Information sources

- Basic systematic search. Common (basic) literature search strategy was used, run for the whole project and described in COL Appendix 1;

- Hand search;

- Additional search for published literature in PubMed and internet search of grey literature using Google search engine;

- Review of the reference lists and bibliographies of studies identified through the basic systematic search;

- International Organisations’ websites (OECD, WHO, NICE etc.);

- Manufacturers web sites;

- Company brochures and Information for use;

-  Survey: two questionnaires were administered, to EUnetHTA Partners and Manufacturers (more information in COL Appendix 2), with aim to get further information about primary CRC screening methods and tests in different EU countries; please see in COL Appendix 2.

Quality assessment tools or criteria

No quality assessment tool was used, but multiple sources were used in order to validate individual, possibly biased, sources.

Analysis and synthesis

Descriptive analysis was performed on different information sources. The assessment elements questions are answered by cooperation of Domain investigators.

Results cards are covered by evidence gathered from basic search (COL Appendix 1), hand searched literature, manufacturers web sites, company brochures and information for use, and survey (questionnaire) results.

 

Result cards

Target Condition

Result card for CUR1: "Which disease/health problem/potential health problem will FIT be used for?"

View full card
CUR1: Which disease/health problem/potential health problem will FIT be used for?
Result

Importance: Critical

Transferability: Completely

Result card for CUR2: "What, if any, is the precise definition/ characterization of adenomas and/or colorectal carcinoma (CRC)? Which diagnosis is given to the condition and according to which classification system (e.g. ICD-10)?"

View full card
CUR2: What, if any, is the precise definition/ characterization of adenomas and/or colorectal carcinoma (CRC)? Which diagnosis is given to the condition and according to which classification system (e.g. ICD-10)?
Result

Importance: Critical

Transferability: Completely

Result card for CUR4: "Which are the known risk factors for acquiring adenomas and/or CRC?"

View full card
CUR4: Which are the known risk factors for acquiring adenomas and/or CRC?
Result

Importance: Important

Transferability: Partially

Result card for CUR6: "What is the natural course of CRC?"

View full card
CUR6: What is the natural course of CRC?
Result

Importance: Critical

Transferability: Completely

Result card for CUR8: "What are the symptoms at different stages of adenomas and/or CRC?"

View full card
CUR8: What are the symptoms at different stages of adenomas and/or CRC?
Result

Importance: Critical

Transferability: Completely

Result card for CUR9: "What is the burden of CRC?"

View full card
CUR9: What is the burden of CRC?
Result
Comment

Importance: Critical

Transferability: Partially

Result card for CUR11: "What aspects of the burden of CRC are targeted by CRC screening with FIT?"

View full card
CUR11: What aspects of the burden of CRC are targeted by CRC screening with FIT?
Result

Importance: Critical

Transferability: Completely

Target Population

Result card for CUR10: "What is the target population for colorectal carcinoma screening with FIT?"

View full card
CUR10: What is the target population for colorectal carcinoma screening with FIT?
Result

Importance: Critical

Transferability: Partially

Result card for CUR26: "How many people belong to the target population in Europe?"

View full card
CUR26: How many people belong to the target population in Europe?
Result

Importance: Critical

Transferability: Not

Utilisation

Result card for CUR12: "Which countries use FIT for CRC screening?" and CUR13: "Which percentage of target population is accually screened in countries with CRC screening program with FIT?"

View full card
CUR12: Which countries use FIT for CRC screening?
Method
Result

Importance: Important

Transferability: Partially

CUR13: Which percentage of target population is accually screened in countries with CRC screening program with FIT?
Result

Importance: Critical

Transferability: Partially

Result card for CUR14: "What kind of variations in use of CRC screening methods are there across countries/regions/settings?"

View full card
CUR14: What kind of variations in use of CRC screening methods are there across countries/regions/settings?
Result
Comment

Importance: Important

Transferability: Partially

Current Management of the Condition

Result card for CUR15: "How are adenomas/CRC currently diagnosed?" and CUR16: "How are adenomas/CRC currently screened?"

View full card
CUR15: How are adenomas/CRC currently diagnosed?
Result

Importance: Important

Transferability: Partially

CUR16: How are adenomas/CRC currently screened?
Result

Importance: Important

Transferability: Partially

Result card for CUR17: "How should adenomas/CRC be diagnosed or screened according to published algorithms/guidelines?"

View full card
CUR17: How should adenomas/CRC be diagnosed or screened according to published algorithms/guidelines?
Result

Importance: Important

Transferability: Partially

Result card for CUR18: "How are adenomas/CRC currently managed?"

View full card
CUR18: How are adenomas/CRC currently managed?
Result

Importance: Important

Transferability: Partially

Result card for CUR20: "How should adenomas/CRC be managed according to published algorithms/guidelines?"

View full card
CUR20: How should adenomas/CRC be managed according to published algorithms/guidelines?
Result

Importance: Important

Transferability: Partially

Result card for CUR21: "What are the differences in the management for different stages of CRC?"

View full card
CUR21: What are the differences in the management for different stages of CRC?
Result

Importance: Important

Transferability: Partially

Result card for CUR22: "What are the other evidence-based alternatives to CRC screening with FIT?" and CUR27: "What are the technical characteristics and analytical validity of guaiac-based fecal occult blood test (FOBT), as main CRC screening comparator in this assessment?"

View full card
CUR22: What are the other evidence-based alternatives to CRC screening with FIT?
Result

Importance: Important

Transferability: Partially

CUR27: What are the technical characteristics and analytical validity of guaiac-based fecal occult blood test (FOBT), as main CRC screening comparator in this assessment?
Result

Importance: Important

Transferability: Partially

Life-Cycle

Result card for CUR23: "In which phase is the development of FIT?"

View full card
CUR23: In which phase is the development of FIT?
Result

Importance: Important

Transferability: Completely

Regulatory Status

Result card for CUR24: "Which market authorization status (CE mark) has FIT in other countries, or international authorities?"

View full card
CUR24: Which market authorization status (CE mark) has FIT in other countries, or international authorities?
Result

Importance: Critical

Transferability: Completely

Result card for CUR25: "What is the reimbursement status of CRC screening with FIT across countries?"

View full card
CUR25: What is the reimbursement status of CRC screening with FIT across countries?
Result

Importance: Important

Transferability: Completely

Discussion

Few limitations were observed during assessment of domain questions. Detailed comparisons were difficult due the fact that not all countries maintain population and cancer registers. Data on incidence and mortality were extracted from the database of the GLOBOCAN project (International Agency for Research on Cancer), which provides contemporary estimates of these measures {6}. The most recent estimates are for 2008. Incidence data also derive from population-based cancer registries. More information on the GLOBOCAN data and sources are available on the project’s website. Regarding CRC survival, results of the EUROCARE project were preferred as it is a project that aims to describe and interpret differences in cancer patient survival in Europe. However, there are limitations to the project, already acknowledged by the researchers {21}. The reader should keep in mind that not all European countries are involved in the EUROCARE project. Furthermore, for several countries cancer registration covers only a fraction of the total national population. The first round (EUROCARE-1) included 30 cancer registry populations diagnosed from 12 European countries. During the rounds that followed more regional and national registries participated. The current, fifth round (EUROCARE-5) includes data from 116 Cancer Registries in 30 European countries and for patients diagnosed during 2000-2007 {39}. Strengths, limitations and the value of findings are discussed in detail by the researchers {21,40}.

Differences among MSs on screening methods, adherence rates, marketing authorization and reimbursement status of the tests were not fully established since in the Survey applied to MSs Partner only 11 countries were answered, and in Survey applied to Manufacturers only one responded.

The most clinically and cost-effective CRC screening method still should be determine in additional comparative effectiveness research. Analytical performance of different FOB tests (gFOBT or FIT) should be keep in mind when make decision on which FOB test should be used for CRC screening as well as compliance and general acceptance of the test by the public.

References

 

1.             Gallagher C, Lister T, Smith M. Malignant disease. In: Kumar P, Clark M, editors. Clinical Medicine 8th ed. Edinburgh: Elsevier; 2012. p. 431-83.

2.             Segnan N, Patnick J, von Karsa L, editors. European guidelines for quality assurance in colorectal cancer screening and diagnosis - First Edition. 1st ed. Luxembourg: Publications Office of the European Union; 2010.

3.             Longo D, Fauci A, Kasper D, Hauser S, Jameson J, Loscalzo J. Colorectal cancer.  Harrison’s manual of medicine. 18th ed. New York: McGraw-Hill; 2013. p. 453-57.

4.             Longo D, Fauci A, Kasper D, Hauser S, Jameson J, Loscalzo J. Obesity.  Harrison’s manual of medicine. 18th ed. New York: McGraw-Hill; 2013. p. 1134-7.

5.             Zavoral M, Suchanek S, Zavada F, Dusek L, Muzik J, Seifert B, et al. Colorectal cancer screening in Europe. World journal of gastroenterology : WJG. 2009 Dec 21;15(47):5907-15. PubMed PMID: 20014454. Pubmed Central PMCID: PMC2795177. Epub 2009/12/17. eng.

6.             Ferlay J, Shin H, Bray F, Forman D, Mathers C, Parkin D. GLOBOCAN 2008 v2.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 [Internet]. Lyon, France: International Agency for Research on Cancer; 2010 [cited 2013 May 15]. Available from: http://globocan.iarc.fr.

7.             Berrino F, De Angelis R, Sant M, Rosso S, Lasota MB, Coebergh JW, et al. Survival for eight major cancers and all cancers combined for European adults diagnosed in 1995–99: results of the EUROCARE-4 study. The Lancet Oncology. 2007 9//;8(9):773-83.

8.             Grande E, Inghelmann R, Francisci S, Verdecchia A, Micheli A, Baili P, et al. Regional estimates of colorectal cancer burden in Italy. Tumori. 2007 Jul-Aug;93(4):352-9. PubMed PMID: 17899865. Epub 2007/09/29. eng.

9.             American Cancer Society. Colorectal Cancer Facts & Figures 2011-2013. Atlanta: American Cancer Society, 2011.

10.          Coleman MP, Gatta G, Verdecchia A, Estève J, Sant M, Storm H, et al. EUROCARE-3 summary: cancer survival in Europe at the end of the 20th century. Annals of Oncology. 2003 December 1, 2003;14(suppl 5):v128-v49.

11.          Verdecchia A, Francisci S, Brenner H, Gatta G, Micheli A, Mangone L, et al. Recent cancer survival in Europe: a 2000?02 period analysis of EUROCARE-4 data. The Lancet Oncology. 2007;8(9):784-96.

12.          Karim-Kos HE, de Vries E, Soerjomataram I, Lemmens V, Siesling S, Coebergh JWW. Recent trends of cancer in Europe: A combined approach of incidence, survival and mortality for 17 cancer sites since the 1990s. European journal of cancer (Oxford, England : 1990). 2008;44(10):1345-89.

13.          Jemal A, Center MM, DeSantis C, Ward EM. Global Patterns of Cancer Incidence and Mortality Rates and Trends. Cancer Epidemiology Biomarkers & Prevention. 2010 August 1, 2010;19(8):1893-907.

14.          Center MM, Jemal A, Ward E. International Trends in Colorectal Cancer Incidence Rates. Cancer Epidemiology Biomarkers & Prevention. 2009 June 1, 2009;18(6):1688-94.

15.          OECD. Health at a Glance: Europe 2012. Paris: OECD Publishing; 2012. Available from: http://ec.europa.eu/health/reports/docs/health_glance_2012_en.pdf.

16.          La Vecchia C, Bosetti C, Lucchini F, Bertuccio P, Negri E, Boyle P, et al. Cancer mortality in Europe, 2000–2004, and an overview of trends since 1975. Annals of Oncology. 2010 June 1, 2010;21(6):1323-60.

17.          Dickman PW, Adami HO. Interpreting trends in cancer patient survival. Journal of internal medicine. 2006 Aug;260(2):103-17. PubMed PMID: 16882274. Epub 2006/08/03. eng.

18.          Sant M, Capocaccia R, Coleman MP, Berrino F, Gatta G, Micheli A, et al. Cancer survival increases in Europe, but international differences remain wide. European journal of cancer (Oxford, England : 1990). 2001;37(13):1659-67.

19.          Verdecchia A, Guzzinati S, Francisci S, De Angelis R, Bray F, Allemani C, et al. Survival trends in European cancer patients diagnosed from 1988 to 1999. European journal of cancer (Oxford, England : 1990). 2009;45(6):1042-66.

20.          Brenner H, Bouvier AM, Foschi R, Hackl M, Larsen IK, Lemmens V, et al. Progress in colorectal cancer survival in Europe from the late 1980s to the early 21st century: the EUROCARE study. International journal of cancer Journal international du cancer. 2012 Oct 1;131(7):1649-58. PubMed PMID: 21607946. Epub 2011/05/25. eng.

21.          Berrino F. The EUROCARE Study: strengths, limitations and perspectives of population-based, comparative survival studies. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2003;14 Suppl 5:v9-13. PubMed PMID: 14684497. Epub 2003/12/20. eng.

22.          Faivre-Finn C, Bouvier-Benhamiche AM, Phelip JM, Manfredi S, Dancourt V, Faivre J. Colon cancer in France: evidence for improvement in management and survival. Gut. 2002 Jul;51(1):60-4. PubMed PMID: 12077093. Pubmed Central PMCID: PMC1773269. Epub 2002/06/22. eng.

23.          Ostenfeld EB, Erichsen R, Iversen LH, Gandrup P, Norgaard M, Jacobsen J. Survival of patients with colon and rectal cancer in central and northern Denmark, 1998-2009. Clinical epidemiology. 2011;3 Suppl 1:27-34. PubMed PMID: 21814467. Pubmed Central PMCID: PMC3144775. Epub 2011/08/05. eng.

24.          Gatta G, Capocaccia R, Sant M, Bell CM, Coebergh JW, Damhuis RA, et al. Understanding variations in survival for colorectal cancer in Europe: a EUROCARE high resolution study. Gut. 2000 Oct;47(4):533-8. PubMed PMID: 10986214. Pubmed Central PMCID: PMC1728079. Epub 2000/09/15. eng.

25.          Engeland A, Haldorsen T, Dickman PW, Hakulinen T, Möller TR, Storm HH, et al. Relative survival of cancer patients--a comparison between Denmark and the other Nordic countries. Acta oncologica (Stockholm, Sweden). 1998 /;37(1):49-59.

26.          Monnet E, Faivre J, Raymond L, Garau I. Influence of stage at diagnosis on survival differences for rectal cancer in three European populations. British journal of cancer. 1999 Oct;81(3):463-8. PubMed PMID: 10507771. Pubmed Central PMCID: PMC2362908. Epub 1999/10/03. eng.

27.          WHO. The global burden of disease: 2004 update. Geneva: World Health Organization 2008.

28.          Glaser AW, Fraser LK, Corner J, Feltbower R, Morris EJ, Hartwell G, et al. Patient-reported outcomes of cancer survivors in England 1-5 years after diagnosis: a cross-sectional survey. BMJ open. 2013;3(4). PubMed PMID: 23578682. Pubmed Central PMCID: PMC3641492. Epub 2013/04/13. eng.

29.          Caravati-Jouvenceaux A, Launoy G, Klein D, Henry-Amar M, Abeilard E, Danzon A, et al. Health-Related Quality of Life Among Long-Term Survivors of Colorectal Cancer: A Population-Based Study. The Oncologist. 2011 November 1, 2011;16(11):1626-36.

30.          Jansen L, Herrmann A, Stegmaier C, Singer S, Brenner H, Arndt V. Health-Related Quality of Life During the 10 Years After Diagnosis of Colorectal Cancer: A Population-Based Study. Journal of Clinical Oncology. 2011 August 20, 2011;29(24):3263-9.

31.          Yost K, Hahn E, Zaslavsky A, Ayanian J, West D. Predictors of health-related quality of life in patients with colorectal cancer. Health Qual Life Outcomes. 2008 2008/08/25;6(1):1-10. English.

32.          Eakin EG, Youlden DR, Baade PD, Lawler SP, Reeves MM, Heyworth JS, et al. Health Status of Long-term Cancer Survivors: Results from an Australian Population-Based Sample. Cancer Epidemiology Biomarkers & Prevention. 2006 October 1, 2006;15(10):1969-76.

33.          Yabroff KR, Lawrence WF, Clauser S, Davis WW, Brown ML. Burden of Illness in Cancer Survivors: Findings From a Population-Based National Sample. Journal of the National Cancer Institute. 2004 September 1, 2004;96(17):1322-30.

34.          Schneider EC, Malin JL, Kahn KL, Ko CY, Adams J, Epstein AM. Surviving colorectal cancer. Cancer. 2007;110(9):2075-82.

35.          Jansen L, Koch L, Brenner H, Arndt V. Quality of life among long-term (>5years) colorectal cancer survivors – Systematic review. European journal of cancer 2010;46(16):2879-88.

36.          Domati F, Rossi G, Benatti P, Roncucci L, Cirilli C, Ponz de Leon M. Long-term survey of patients with curable colorectal cancer with specific reference to the quality of life. Intern Emerg Med. 2011 2011/12/01;6(6):529-35. English.

37.          Trentham-Dietz A, Remington PL, Moinpour CM, Hampton JM, Sapp AL, Newcomb PA. Health-Related Quality of Life in Female Long-Term Colorectal Cancer Survivors. The Oncologist. 2003 August 1, 2003;8(4):342-9.

38.          Ramsey SD, Andersen MR, Etzioni R, Moinpour C, Peacock S, Potosky A, et al. Quality of life in survivors of colorectal carcinoma. Cancer. 2000;88(6):1294-303.

39.          EUROCARE. EUROCARE [Internet]. Istituto Superiore di Sanità - Settore I - Informatica; 2013 [cited 2013 July 27th]. Available from: http://www.eurocare.it/

40.          Berrino F, Verdecchia A, Lutz JM, Lombardo C, Micheli A, Capocaccia R. Comparative cancer survival information in Europe. European journal of cancer (Oxford, England : 1990). 2009 Apr;45(6):901-8. PubMed PMID: 19217771. Epub 2009/02/17. eng.

41.          Medical Advisory Secretariat. Fecal Occult Blood Test for Colorectal Cancer Screening: an evidence-based analysis. Toronto: Medical Advisory Secretariat, Ontario Ministry of Health and Long-Term Care, 2009  Contract No.: 10.

42.          Qaseem A, Denberg TD, Hopkins JRH, Humphrey LL, Levine J, Sweet DE, et al. Screening for Colorectal Cancer: A Guidance Statement From the American College of Physicians. Annals of Internal Medicine. 2012;156(5):378-86.

43.          Moss S, Ancelle-Park R, Brenner H. European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition--Evaluation and interpretation of screening outcomes. Endoscopy. 2012 Sep;44 Suppl 3:SE49-64. PubMed PMID: 23012122. Epub 2012/10/04. eng.

44.          Health Information and Quality Authority. Health technology assessment (HTA) of a population-based colorectal cancer screening programme in Ireland. Dublin: Health Information and Quality Authority, 2009.

45.          Lansdorp-Vogelaar I, van Ballegooijen M, Zauber AG, Habbema JD, Kuipers EJ. Effect of rising chemotherapy costs on the cost savings of colorectal cancer screening. J Natl Cancer Inst. 2009 Oct 21;101(20):1412-22. PubMed PMID: 19779203. Pubmed Central PMCID: PMC2765263. Epub 2009/09/26. eng.

46.          Hewitson P, Glasziou P, Irwig L, Towler B, Watson E. Screening for colorectal cancer using the faecal occult blood test, Hemoccult. The Cochrane database of systematic reviews. 2007 (1):CD001216. PubMed PMID: 17253456. Epub 2007/01/27. eng.

47.          Heresbach D, Manfredi S, D'Halluin P N, Bretagne JF, Branger B. Review in depth and meta-analysis of controlled trials on colorectal cancer screening by faecal occult blood test. European journal of gastroenterology & hepatology. 2006 Apr;18(4):427-33. PubMed PMID: 16538116. Epub 2006/03/16. eng.

48.          Kerr J, Day P, Broadstock M, Weir R, Bidwell S. Systematic review of the effectiveness of population screening for colorectal cancer. The New Zealand medical journal. 2007;120(1258):U2629. PubMed PMID: 17653247. Epub 2007/07/27. eng.

49.          Lansdorp-Vogelaar I, von Karsa L. European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition--Introduction. Endoscopy. 2012 Sep;44 Suppl 3:SE15-30. PubMed PMID: 23012118. Epub 2012/10/04. eng.

50.          Libby G, Brewster DH, McClements PL, Carey FA, Black RJ, Birrell J, et al. The impact of population-based faecal occult blood test screening on colorectal cancer mortality: a matched cohort study. British journal of cancer. 2012 Jul 10;107(2):255-9. PubMed PMID: 22735907. Pubmed Central PMCID: PMC3394992. Epub 2012/06/28. eng.

51.          Allison JE. Colon Cancer Screening Guidelines 2005: the fecal occult blood test option has become a better FIT. Gastroenterology. 2005;129(2):745-8. eng.

52.          International Cancer Screening Network. Inventory of Colorectal Cancer Screening Activities in ICSN Countries, May 2008 [Internet]. 2008 [updated 2009 Feb 09 cited 2013 Aug 09]. Available from: http://appliedresearch.cancer.gov/icsn/colorectal/screening.html.

53.          Zorzi M, Fedato C, Grazzini G, Sassoli de' Bianchi P, Naldoni C, Pendenza M, et al. [Screening for colorectal cancer in Italy, 2010 survey]. Epidemiol Prev. 2012 2012 Nov-Dec;36(6 Suppl 1):55-77. ita.

54.          Saito H. Colorectal cancer screening using immunochemical faecal occult blood testing in Japan. Journal of Medical Screening. 2006 December 1, 2006;13(suppl 1):6-7.

55.          Bryant HE, Fekete SV, Major DH. Pan-Canadian initiatives in colorectal cancer screening: adopting knowledge translation tools to accelerate uptake and impact. Current oncology (Toronto, Ont). 2011 Jun;18(3):111-8. PubMed PMID: 21655157. Pubmed Central PMCID: PMC3108864. Epub 2011/06/10. eng.

56.          Australian Government. National Bowel Cancer Screening Program. About the Bowel Cancer Screening Pilot [Internet]. Australian Government, Department of Health and Aeging; 2013 [updated 2013 Jan 31; cited 2013 Aug 9]. Available from: http://www.cancerscreening.gov.au/internet/screening/publishing.nsf/Content/pilot.

57.          Swan H, Siddiqui AA, Myers RE. International Colorectal Cancer Screening Programs: Population Contact Strategies, Testing Methods and Screening Rates. Practical Gastroenterology. 2012;XXXVI(8):8.

58.          von Karsa L, Anttila A, Ronco G, Ponti A, Malila N, Arbyn M, et al. Cancer Screening in the European Union. Report on the implementation of the Council Recommendation on cancer screening. First Report. Luxembourg: WHO International Agency for Research on Cancer, 2008.

59.          Von Karsa L. Colorectal Cancer Screening in Europe. European Guidelines Workshop: National Centre for Screening Monitoring and Italian Colorectal Cancer Screening Group.

60.          United European Gastroenterology. Real progress in colorectal cancer screening in Europe as Estonia develops ‘road map’ for population-based programme [Internet]. 2012 [cited 2013 Aug 9]. Available from: http://www.ueg.eu/news-press/releases/ueg-press-release/article/real-progress-in-colorectal-cancer-screening-in-europe-as-estonia-develops-road-map-for-popula/.

61.          Medical Advisory Secretariat. Screening Methods for Early Detection of Colorectal Cancers and Polyps. Summary of Evidence-Based Analyses. Toronto: Medical Advisory Secretariat, Ontario Ministry of Health and Long-Term Care, 2009  Contract No.: 6.

62.          Lin JS, Webber EM, Beil TL, Goddard KA, Whitlock EP. Fecal DNA Testing in Screening for Colorectal Cancer in Average-Risk Adults 2012 2012 Feb. Report No.

63.          NICE. Colorectal cancer: the diagnosis and management of colorectal cancer. London: National Institute for Health and Care Excellence, 2011.

64.          SIGN. Diagnosis and management of colorectal cancer. Edinburgh: Scottish Intercollegiate Guidelines Network, 2011  Contract No.: 126.

65.          Telford JJ. Canadian guidelines for colorectal cancer screening. Canadian journal of gastroenterology = Journal canadien de gastroenterologie. 2011;25(9):479-81. eng.

66.          U.S. Preventive Services Task Force. Screening for Colorectal Cancer. Recommendation Statement. Internet. March 2009.

67.          Rex DK, Johnson DA, Anderson JC, Schoenfeld PS, Burke CA, Inadomi JM. American College of Gastroenterology guidelines for colorectal cancer screening 2009 [corrected]. The American journal of gastroenterology. 2009 Mar;104(3):739-50. PubMed PMID: 19240699. Epub 2009/02/26. eng.

68.          Levin B, Lieberman DA, McFarland B, Smith RA, Brooks D, Andrews KS, et al. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. CA: a cancer journal for clinicians. 2008;58(3):130-60. eng.

69.          Imperiale TF, Ransohoff DF, Itzkowitz SH, Turnbull BA, Ross ME. Fecal DNA versus Fecal Occult Blood for Colorectal-Cancer Screening in an Average-Risk Population. New England Journal of Medicine. 2004;351(26):2704-14. PubMed PMID: 15616205.

70.          Mandel JS, Bond JH, Church TR, Snover DC, Bradley GM, Schuman LM, et al. Reducing Mortality from Colorectal Cancer by Screening for Fecal Occult Blood. New England Journal of Medicine. 1993;328(19):1365-71. PubMed PMID: 8474513.

71.          Lin J, Webber E, Beil T, Goddard K, EP W. Fecal DNA Testing in Screening for Colorectal Cancer in Average-Risk Adults. Rockville, MD: Agency for Healthcare Research and Quality, 2012  Contract No.: AHRQ Publication 12-EHC022-EF.

72.          Elmunzer BJ, Hayward RA, Schoenfeld PS, Saini SD, Deshpande A, Waljee AK. Effect of Flexible Sigmoidoscopy-Based Screening on Incidence and Mortality of Colorectal Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. PLoS Med. 2012;9(12):e1001352.

73.          Quintero E, Castells A, Bujanda L, Cubiella J, Salas D, Lanas Α, et al. Colonoscopy versus fecal immunochemical testing in colorectal-cancer screening. The New England journal of medicine.

74.          NHS Centre for Evidence-based Purchasing. Evaluation report: Immunohistocemical faecal occult blood tests. NHS Purchasing and Supply Agency, 2009 CEP09042.

75.          von Karsa L, Patnick J, Segnan N, Atkin W, Halloran S, Lansdorp-Vogelaar I, et al. European guidelines for quality assurance in colorectal cancer screening and diagnosis: overview and introduction to the full supplement publication. Endoscopy. 2013;45(1):51-9. PubMed PMID: 23212726. Epub 2012/12/06. eng.

76.          Whyte S, Chilcott J, Cooper K, Essat M, Stevens J, Wong R, et al. Re-appraisal of the options for colorectal cancer screening. Report for the NHS Bowel Cancer Screening Programme. Sheffield: University of Sheffield, School of Health and related Research, 2011.

77.          Young G. Fecal Immunochemical Tests (FIT) vs. Office-Based Guaiac Fecal Occult Blood Test (FOBT). Practical Gastroenterology. 2004;XXVIII(6).

78.          Corp. ES. Top-Line Data Show Exact Sciences' Cologuard Test Demonstrates 92 Percent Sensitivity in the Detection of Colorectal Cancer [Internet]. 2013 [updated 2013, April 18; cited 2013 Aug 9]. Available from: http://investor.exactsciences.com/releasedetail.cfm?ReleaseID=757341.

79.          ClinicalTrial.gov. Multi-Target Colorectal Cancer Screening Test for the Detection of Colorectal Advanced Adenomatous Polyps and Cancer (DeeP-C) [Internet]. U.S. National Institutes of Health; 2013 [updated 2013, Jun 18; cited 2013 Aug 9]. Available from: http://prsinfo.clinicaltrial.gov/ct2/show/record/NCT01397747?id=NCT01397747&rank=1).

 

 

 

 

 

 

Description and technical characteristics of technology

Authors: Mirjana Huic, Eleftheria Karampli, Silvia Florescu, Cristian Vladescu

Summary

Aim To describe and review the technical characteristics of iFOBT.

Methods The Project scope is applied in this Domain. Results cards are covered by evidence gathered from basic literature search, hand searched literature, manufacturers web sites, company brochures and information for use, and survey (questionnaire) results. No quality assessment tool was used, but multiple sources were used in order to validate individual, possibly biased, sources. Descriptive analysis was performed on different information sources. The assessment elements questions are answered by cooperation of Domain investigators.

Results FITs or iFOBTs are a class of faecal occult blood tests (tests for blood or blood products). They use blood as an indicator of the presence of tumour. FOBTs are recommended for population-based colorectal carcinoma screening (CRC) screening. The target group is asymptomatic people at average risk, of both genders. Regarding the age-range, there is evidence endorsing the provision of CRC screening to average-risk individuals, beginning at age 50, to detect cancers at a favourable stage before they have advanced to a potentially lethal disease state.

The first FOBTs that were developed were guaiac-based (gFOBTs). FITs use antibodies raised against human haemoglobin (Hb) to detect human blood present in faeces. New technologies in the field of FOBTs include faecal DNA tests, the use of RNA markers in stool as well as the use of DNA or RNA in plasma, serum and urine. Much work is still ongoing on use of protein biomarkers in blood for CRC screening and early detection.

The advantages of FIT in contrast to gFOBT are: specificity for human Hb, reducing the number of false positive results; no dietetic restrictions necessary; increased sensitivity to human Hb; automated analysis and the possibility to set cut-off limits (the latter applies only to quantitative FIT tests). Disadvantages include sample instability in liquid collection devices, therefore shorter transportation time frame is required; possible additional requirements for packaging of the liquid sample collection devices to meet different MSs postal regulation; and cost of the test. These characteristics should be taken into account in the development of CRC screening programmes in different settings.

A wide range of qualitative and quantitative iFOBT tests is presently available, with varying levels of sensitivity and specificity. Similar to gFOBT, participants collect one or more stool samples, which can be analysed either using automated systems in the laboratory (for some manufacturers) or are read by the naked eye with a positive result indicated by a colour change on a strip. Automated systems can be qualitative (providing dichotomous result) or quantitative (user-defined cut-off levels). In HTAs performed in other countries, automated FITs were considered appropriate for assessment for a population-based screening programme; this approach was also adopted in the present Core HTA. Three iFOBT are presented here, as three analytical platforms using the three sample collection devices: OC-Sensor/OC-Sensor Diana & OC-Sensor Micro, Hem-SP/MagStream HT, FOB Gold/SENTiFOB analyser.

In the framework of a CRC programme using FIT as the primary screening method, users of the technology include people invited to participate in the programme as well as the health professionals who are involved (primary care physicians and nurses, laboratory staff). Parameters that should be taken into account when using FIT in CRC programmes are the material investments needed (procurement and maintenance of laboratory analysers, sample collection devices, refrigerated storage spaces, waste disposal systems and, in some cases, end-of-life disposal), and training needs of the laboratory staff. Laboratory staff training depends on the type of test to be used. Qualification, training and quality assurance processes needed relate to those required in a CRC screening with FOBT. Individuals invited to participate in the programme should be provided with specific instructions on how to use the test kit. It is important that the participant is able to understand written instructions on how to perform these procedures (apart from written material, visual communication instruments and/or oral interventions can be used to facilitate understanding). Furthermore, information about CRC screening risks and benefits, CRC risks, meaning of test results, potential diagnostic tests and potential treatment options should be provided to the patients.

As is the case in every CRC screening programme, several kinds of data need to be recorded. Specifically, records should include: data on each individual and every screening test performed, test results, decision made as a consequence, diagnostic and treatment procedures and subsequent outcome (including cause of death).

Important for practice: In different settings, individual device characteristics like ease of use by participant and laboratory, suitability for transport, sampling reproducibility and sample stability are important and should be all taken into account when selecting the iFOBT most appropriate for CRC screening programme.

Introduction

Faecal Immunochemical Tests (FITs), also known as Immunochemical Faecal Occult Blood Test (iFOBTs), are a newer class of Faecal Occult Blood tests (the first FOBTs developed and marketed were gFOBTs). According the EU Guideline for quality assurance in CRC screening and diagnosis (2010), iFOBT have improved test characteristics than gFOBT. iFOBTs have been used for population CRC screening in Japan since 1992. In the US, the first iFOBT (OC-Sensor) has been approved by the FDA (Food and Drug Administration) since 2001. The aim of population-based screening for CRC is to reduce morbidity and mortality from CRC through both, prevention (by the removal of adenomas before they had a chance to become malignant, so CRC incidence is reduced) and earlier diagnosis of CRC (at early, curable stage).

A wide range of qualitative and quantitative FITs is presently available, with varying levels of sensitivity and specificity. They all use antibodies raised against human haemoglobin (Hb) to detect human blood present in faeces.

The older class of faecal occult blood tests, guaiac-based fecal occult blood tests (gFOBTs) has proven characteristics that make them suitable for population CRC screening. The advantages and disadvantages of both, gFOBTs and iFOBTs should be taken into account in the development of CRC screening programmes in different settings, like local labour costs, the mechanism of kit distribution and collection as well as the sample stability characteristics.

The aim of this Domain is to describe and review the technical characteristics of iFOBT.

Methodology

Frame

The collection scope is used in this domain.

TechnologyFecal Immunochemical Test (FIT) for colorectal cancer screening
Description

FITs use an antibody (immunoglobulin) specific to human globin, the protein component of haemoglobin, to detect fecal occult blood. Immunochemical tests have improved test characteristics compared to conventional guaiac-based tests for fecal occult blood. FIT should not be subject to interference from dietary blood and it is more specific to bleeding from the distal gastrointestinal tract. They could be analytically and clinically more sensitive and specific, Their measurement can be automated and the user can adjust the concentration at which a positive result is reported. A wide range of qualitative and quantitative tests is presently available, with varying levels of sensitivity and specificity (like Hem-SP/MagStream H, Fujirebio Inc. Japan ; OC-Sensor, Eiken Chemical Co., Tokyo, Japan;    FOB Gold, Medinostics Products Supplier; Sentinel Diagnostics SpA, Milan, Italy).

Intended use of the technologyScreening

CRC screening with faecal inmunochemical test (FIT) for detection of occult blood in the stool associated with colorectal lesions (adenomas and CRC).

The use of the test is considered under conditions of population based colorectal cancer screening, in the context of organised cancer screening programmes as recommended by the EU. Early detection and treatment of colorectal lesions before they become symptomatic has the potential to improve control of the disease, reducing morbidity and mortality associated to CRC. Early treatment of invasive lesions can be generally less detrimental for quality of life. The endoscopic removal of pre-malignant lesions also reduces the incidence of CRC by stopping the progression to cancer. Colorectal cancers and adenomatous polyps bleed has providing fecal blood haemoglobin as the biomarker of choice for current screening programmes. Stool samples could be periodically taken and analyzed for the presence of occult blood, as an early sign of colorectal lesions (adenoma or CRC).

Target condition
Adenomas, as non-malignant precursor lesions of ColoRectal Cancer (CRC).
Target condition description

CRC is the third most common in incidence and the fourth most common cause of cancer death worldwide. CRC is particularly suitable for screening. The disease is believed to develop in a vast majority of cases from non-malignant precursor lesions called adenomas. Adenomas can occur anywhere in the colorectum after a series of mutations that cause neoplasia of the epithelium. At some time , the adenoma may invade the submucosa and become malignant. Initially, this malignant cancer is not diagnosed and does not give symptoms  (preclinical phase). It can progress from localised (stage I) to metastasised (stage IV) cancer, until it causes symptoms and is diagnosed. Only 5–6% of the population actually develop CRC. The average duration of the development of an adenoma to CRC is estimated to be  at least 10 years. This long latent phase provides a window of opportunity for early detection of the disease.

Target population

Target population sex: Any. Target population age: adults and elderly. Target population group: Healthy and/or asymptomatic people.

Target population description

Adults, average risk of CRC, aged 50 years or over.

The best age range for offering gFOBT or FIT screening has not been investigated in trials. Circumstantial evidence suggests that mortality reduction from gFOBT is similar in different age ranges between 45 and 80 years .The age range for a national screening programme should at least include people aged 60 to 64 years in which CRC incidence and mortality are high and life-expectancy is still considerable. Only the FOBT for men and women aged 50–74 years has been recommended todate by the EU (Council Recommendation and the European guidelines for quality assurance in CRC screening and diagnosis).

Members of families with hereditary syndromes, previous diagnosis of CRC or pre-malignant lesions should follow specific surveillance protocols and are not included in the target population

ComparisonCRC screening with Guaiac –based fecal occult blood test (gFOBT)
Description

CRC screening with Guaiac–based fecal occult blood test (gFOBT)

The guaiac-based FOBT is still a commonly used method for detecting blood in faeces. To detect hemoglobin the test uses guaiac gum and its efficacy as a colorectal cancer screening test has been analyzed in several randomised controlled trials. The test detects the haem component of haemoglobin, which is identical across human and animal species and is chemically robust and only partially degraded during its passage through the gastrointestinal tract. gFOBTs cannot distinguish between human blood and blood residues from the diet.

Many guaiac-based tests are currently on the market (like Coloscreen, Helena Laboratories,Texas,USA; Hema-screen Immunostics Inc.; Hemoccult, Beckman Coulter Inc.; Hemoccult SENSA, Beckman Coulter Inc.; MonoHaem, Chemicon Europe Ltd; Hema-Check, Siemens PLC; HemaWipe, Medtek Diagnostics LLC)

The use of the test is considered under conditions of population based colorectal cancer screening, in the context of organised cancer screening programmes as recommended by the EU. Population-based programmes have been rolled out nationwide in several European countries. Many member states  haveestablished nationwide non-population-based programmes. Some states are planning or piloting a nationwide population-based programme. These have  adopted only FOBT, some only FIT, some a mix between FOBT and endoscopy, or only colonoscopy.

Outcomes

CUR and TEC

  • Health problems (target condition)
  • Epidemiology
  • Burden of disease
  • Target population
  • Current management of the condition
  • Features of the technology
  • Life-Cycle
  • Regulatory status
  • Utilization
  • Investments and tools required to use the technology
  • Training and information needed to use the technology

SAF

  • Colonoscopy probability of perforation
  • Colonoscopy with polypectomy probability of perforation
  • Colonoscopy probability of death following perforation
  • Probability of bleeding following colonoscopy
  • Psychological harms from false-negatives and false-positives (and generally from participating in screening program)

EFF

  • Test (FIT and gFOBT) sensitivity for adenomas
  • Test (FIT and gFOBT) sensitivity for cancer
  • Test (FIT and gFOBT) specificity for adenomas
  • Test (FIT and gFOBT) specificity for cancer 
  • Adenoma incidence (detection rates)
  • Rectal cancer incidence (detection rates)
  • Colon cancer incidence (detection rates)
  • CRC incidence (detection rates)
  • Stage distribution of detected cancers
  • Rectal cancer specific mortality
  • CRC specific mortality
  • Overall mortality
  • Life years saved

ECO:

  • Model/template for  national pilots  to assess the costs and benefits of the two alternative  technologies FIT and gFOBT  and also no-programmed-screening
  • Systematic literature search of   available models and/or economic  evaluation for screening colorectal cancer with FIT and gFOBT and no screening programme
  • Resource Utilization: Publicly funded health care payer costs (screening tests, further examinations e.g. labor, colonoscopy  and treatments and administration and organisation costs of screening programme) for FIT and gFOBT (in cooperation with ORG)
  • Cost per Case detected (average, marginal, incremental) =  intermediate outcome – optional, not decided yet (relevant for deciding how often a test should be carried out and what are the incremental costs for a “new” detected case
  • Indirect Costs: not for the Core modell (should be decided later on)
  • Test accuracy: from SAF
  • Cost effectiveness analysis: HRQoL measures (both generic and context specific) (EFF and SAF for help, own Lit.research), ICER

 ORG:

  • Responsiveness of target population to invitation
  • Invitation-reminder system
  • Competence of human resources – health professionals
  • Investments needed (material,equipment)
  • Costs of using both tests (FIT, gFOBT)
  • Timeliness of results and future phases
  • Use of tools for process monitoring (completed check lists)
  • Model for Budget Impact Analysis from perspective of the payer

SOC

  • Compliance with the tests (FIT, gFOBT)
  • Anxiety and any psychological effects of using  one test or another
  • Information, counseling, communication (quality of) for the use of tests
  • Satisfaction  
  • Quality of life
  • Equity of access

LEG

  • Information as baseline for an informed consent
  • Harms or inequities that can be taken to court

Assessment elements

TopicIssue RelevantResearch questions or rationale for irrelevance
B0001Features of the technologyWhat is this technology?yesWhat is FIT?
B0002Features of the technologyWhy is this technology used?yesWhy is FIT used?
B0003Features of the technologyWhat is the phase of the technology?yesWhat is the phase of FIT?
B0004Features of the technologyWho will apply this technology?yesWho will apply FIT?
B0005Features of the technologyIn what place and context is the technology intended to be used?yesIn what place and context is FIT intended to be used?
B0006Features of the technologyAre there any special features relevant to this technology?yesAre there any special features relevant to FIT?
B0016Features of the technologyTo what population(s) will this technology be used on?yesTo what population(s) will FIT be used on?
B0017Features of the technologyIs this technology field changing rapidly?yesIs FIT field changing rapidly?
B0018Features of the technologyAre the reference values or cut-off points clearly established?yesAre the reference values or cut-off points clearly established?
B0007Investments and tools required to use the technologyWhat material investments are needed to use the technology?yesWhat material investments are needed to use FIT?
B0008Investments and tools required to use the technologyWhat kind of special premises are needed to use the technology?yesWhat kind of special premises are needed to use FIT?
B0009Investments and tools required to use the technologyWhat equipment and supplies are needed to use the technology?yesWhat equipment and supplies are needed to use FIT?
B0010Investments and tools required to use the technologyWhat kind of data and records are needed to monitor the use the technology?yesWhat kind of data and records are needed to monitor the use FIT?
B0011Investments and tools required to use the technologyWhat kind of registers are needed to monitor the use the technology?yesWhat kind of registers are needed to monitor the use FIT?
B0012Training and information needed to use the technologyWhat kind of qualification, training and quality assurance processes are needed for the use or maintenance of the technology?yesWhat kind of qualification, training and quality assurance processes are needed for the use or maintenance of FIT?
B0013Training and information needed to use the technologyWhat kind of training is needed for the personnel treating or investigating patients using this technology?yesWhat kind of training is needed for the personnel treating or investigating patients using FIT?
B0014Training and information needed to use the technologyWhat kind of training and information should be provided for the patient who uses the technology, or for his family/carer?yesWhat kind of training and information should be provided for the patient who uses FIT, or for his family/carer?
B0015Training and information needed to use the technologyWhat information of the technology should be provided for patients outside the target group and the general public?yesWhat information of FIT should be provided for patients outside the target group and the general public?

Methodology description

Domain frame

The Project scope is applied in this domain.

Information sources

- Basic systematic search. Common (basic) literature search strategy was used, run for the whole project and described in COL Appendix 1;

- Additional search for published literature in PubMed and internet search of grey literature using Google search engine;

- Review of the reference lists and bibliographies of studies identified through the basic systematic search;

- Manufacturers web sites;

- Company brochures and Information for use;

Survey: two questionnaires were administered, to EUnetHTA partners and Manufacturers (more information in COL Appendix 2), with aim to get further information about primary CRC screening methods and tests in different EU countries; please see in COL Appendix 2.

Quality assessment tools or criteria

No quality assessment tool was used, but multiple sources were used in order to validate individual, possibly biased, sources.

Analysis and synthesis

Descriptive analysis was performed on different information sources. The assessment elements questions are answered by cooperation of Domain investigators.

Results cards are covered by evidence gathered from basic search (COL Appendix 1), hand searched literature, manufacturers web sites, company brochures and information for use, and survey (questionnaire) results.

Result cards

Features of the technology

Result card for TEC1: "What is FIT?"

View full card
TEC1: What is FIT?
Result

Importance: Critical

Transferability: Completely

Result card for TEC2: "Why is FIT used?"

View full card
TEC2: Why is FIT used?
Result

Importance: Critical

Transferability: Partially

Result card for TEC3: "What is the phase of FIT?"

View full card
TEC3: What is the phase of FIT?
Result

Importance: Important

Transferability: Completely

Result card for TEC4: "Who will apply FIT?"

View full card
TEC4: Who will apply FIT?
Result

Importance: Important

Transferability: Partially

Result card for TEC5: "In what place and context is FIT intended to be used?"

View full card
TEC5: In what place and context is FIT intended to be used?
Result

Importance: Important

Transferability: Partially

Result card for TEC6: "Are there any special features relevant to FIT?"

View full card
TEC6: Are there any special features relevant to FIT?
Result

Importance: Important

Transferability: Partially

Result card for TEC16: "To what population(s) will FIT be used on?"

View full card
TEC16: To what population(s) will FIT be used on?
Result

Importance: Critical

Transferability: Partially

Result card for TEC17: "Is FIT field changing rapidly?"

View full card
TEC17: Is FIT field changing rapidly?
Result

Importance: Important

Transferability: Completely

Result card for TEC18: "Are the reference values or cut-off points clearly established?"

View full card
TEC18: Are the reference values or cut-off points clearly established?
Result

Importance: Critical

Transferability: Completely

Investments and tools required to use the technology

Result card for TEC7: "What material investments are needed to use FIT?"

View full card
TEC7: What material investments are needed to use FIT?
Result

Importance: Important

Transferability: Partially

Result card for TEC8: "What kind of special premises are needed to use FIT?"

View full card
TEC8: What kind of special premises are needed to use FIT?
Result

Importance: Important

Transferability: Partially

Result card for TEC9: "What equipment and supplies are needed to use FIT?"

View full card
TEC9: What equipment and supplies are needed to use FIT?
Result

Importance: Important

Transferability: Partially

Result card for TEC10: "What kind of data and records are needed to monitor the use FIT?"

View full card
TEC10: What kind of data and records are needed to monitor the use FIT?
Result

Importance: Important

Transferability: Partially

Result card for TEC11: "What kind of registers are needed to monitor the use FIT?"

View full card
TEC11: What kind of registers are needed to monitor the use FIT?
Result

Importance: Important

Transferability: Partially

Training and information needed to use the technology

Result card for TEC12: "What kind of qualification, training and quality assurance processes are needed for the use or maintenance of FIT?"

View full card
TEC12: What kind of qualification, training and quality assurance processes are needed for the use or maintenance of FIT?
Result

Importance: Important

Transferability: Partially

Result card for TEC13: "What kind of training is needed for the personnel treating or investigating patients using FIT?"

View full card
TEC13: What kind of training is needed for the personnel treating or investigating patients using FIT?
Result

Importance: Important

Transferability: Partially

Result card for TEC14: "What kind of training and information should be provided for the patient who uses FIT, or for his family/carer?"

View full card
TEC14: What kind of training and information should be provided for the patient who uses FIT, or for his family/carer?
Result

Importance: Critical

Transferability: Partially

Result card for TEC15: "What information of FIT should be provided for patients outside the target group and the general public?"

View full card
TEC15: What information of FIT should be provided for patients outside the target group and the general public?
Result

Importance: Important

Transferability: Partially

Discussion

Some limitations were observed during assessment of domain questions. Authors recognized importance of appropriate stakeholders’ involvement, but only one Manufacturer responded on our questions. Some assessment element questions are overlapping with assessment element questions in Health problem and current use of the technology (CUR) Domain; some should be placed in different order and some are very similar or almost identical in meaning. Authors suggest that assessment elements questions and results cards CUR 23, 24 and 25 should belong to Technical description and characteristics of the technology (TEC) Domain, as well as CUR 27. Referencing to other results cards is used to minimize duplication. Transferability judgement will be mostly appropriately done by HTA doers at national levels, according the core HTA data presented here.

Important for practice: In different settings, individual device characteristics like ease of use by participant and laboratory, suitability for transport, sampling reproducibility and sample stability are important and should be all taken into account when selecting the iFOBT most appropriate for CRC screening programme.

References

1.         Young GP, St John DJ, Winawer SJ, Rozen P. Choice of fecal occult blood tests for colorectal cancer screening: recommendations based on performance characteristics in population studies: a WHO (World Health Organization) and OMED (World Organization for Digestive Endoscopy) report. The American journal of gastroenterology. 2002;97(10):2499-507. eng.

2.         Rabeneck L, Rumble RB, Thompson F, Mills M, Oleschuk C, Whibley A, et al. Fecal immunochemical tests compared with guaiac fecal occult blood tests for population-based colorectal cancer screening. Canadian Journal of Gastroenterology. 2012;26(3):131-47. eng.

3.         Health Information and Quality Authority. Health technology assessment (HTA) of a population-based colorectal cancer screening programme in Ireland. Dublin: Health Information and Quality Authority, 2009.

4.         Rabeneck L RR, Thompson F, Mills M, Oleschuk C, Whibley AH, et al. Fecal immunochemical tests compared with guaiac fecal occult blood tests for population-based colorectal cancer screening. Toronto, ON: Cancer Care Ontario, 2011 Nov 8  Contract No.: Program in Evidence-based Care Evidence-based Series No.: 15-8.

5.         NHS Centre for Evidence-based Purchasing. Evaluation report: Immunohistocemical faecal occult blood tests. NHS Purchasing and Supply Agency, 2009 CEP09042.

6.         Segnan N, Patnick J, von Karsa L, editors. European guidelines for quality assurance in colorectal cancer screening and diagnosis - First Edition. 1st ed. Luxembourg: Publications Office of the European Union; 2010.

7.         Whyte S, Chilcott J, Cooper K, Essat M, Stevens J, Wong R, et al. Re-appraisal of the options for colorectal cancer screening. Report for the NHS Bowel Cancer Screening Programme. Sheffield: University of Sheffield, School of Health and related Research, 2011.

8.         Guittet L, Guillaume E, Levillain R, Beley P, Tichet J, Lantieri O, et al. Analytical comparison of three quantitative immunochemical fecal occult blood tests for colorectal cancer screening. Cancer Epidemiol Biomarkers Prev. 2011 2011 Jul;20(7):1492-501. eng.

9.         von Karsa L, Patnick J, Segnan N, Atkin W, Halloran S, Lansdorp-Vogelaar I, et al. European guidelines for quality assurance in colorectal cancer screening and diagnosis: overview and introduction to the full supplement publication. Endoscopy. 2013;45(1):51-9. eng.

10.       van Rossum LGM, van Rijn AF, van Oijen MGH, Fockens P, Laheij RJF, Verbeek ALM, et al. False negative fecal occult blood tests due to delayed sample return in colorectal cancer screening. International Journal of Cancer. 2009;125(4):746-50.

11.       Young GP. Fecal immunochemical tests (FIT) vs. office-based guaiac fecal occult blood test (FOBT). Pract Gastroenterol. 2004 2004;28(6):46-56.

12.       Lin J, Webber E, Beil T, Goddard K, EP W. Fecal DNA Testing in Screening for Colorectal Cancer in Average-Risk Adults. Rockville, MD: Agency for Healthcare Research and Quality, 2012  Contract No.: AHRQ Publication 12-EHC022-EF.

13.       Exact Sciences Corp. Top-Line Data Show Exact Sciences' Cologuard Test Demonstrates 92 Percent Sensitivity in the Detection of Colorectal Cancer. [Internet]. 2013, April 18 [cited 2013 Aug 9]. Available from: http://investor.exactsciences.com/releasedetail.cfm?ReleaseID=757341.

14.       ClinicalTrials.gov. Multi-Target Colorectal Cancer Screening Test for the Detection of Colorectal Advanced Adenomatous Polyps and Cancer (DeeP-C) [Internet]. U.S. National Institutes of Health; 2013, Jun 18 [cited 2013 Aug 9]. Available from: http://prsinfo.clinicaltrial.gov/ct2/show/record/NCT01397747?id=NCT01397747&rank=1).

15.       Council of the European Union. Recommendation of 2 December 2003 on cancer screening. 2003/878/EC. Off J Eur Union. 2003:34–8.

16.       Medical Advisory Secretariat. Screening Methods for Early Detection of Colorectal Cancers and Polyps. Summary of Evidence-Based Analyses. Toronto: Medical Advisory Secretariat, Ontario Ministry of Health and Long-Term Care, 2009  Contract No.: 6.

17.       Epigenomics AG. Epigenomics AG submits the fourth module and completes its PMA submission to the FDA for Epi proColon®. [Internet]. Epigenomics AG,; 2013, Jan 7 [cited 2013 Oct 26]. Available from: http://clinicaltrials.gov/ct2/show/record/NCT01580540.

18.       ClinicalTrials.gov. Head to Head Study Epi proColon and FIT. [Internet]. U.S. National Institutes of Health; 2013 [updated 2013, Feb 6; cited 2013 Oct 26]. Available from: http://clinicaltrials.gov/ct2/show/record/NCT01580540.

19.       Epigenomics AG. Results of Comparative Study between Epigenomics Epi proColon® and FIT to be Presented at Digestive Disease Week. [Internet]. Epigenomics AG,; 2013, Mar 15 [updated 2011; cited 2013 Oct 26]. Available from: http://clinicaltrials.gov/ct2/show/record/NCT01580540.

20.       van Rossum LGM, van Rijn AF, Laheij RJF, van Oijen MGH, Fockens P, Jansen JBMJ, et al. Cutoff value determines the performance of a semi-quantitative immunochemical faecal occult blood test in a colorectal cancer screening programme. British journal of cancer. 2009;101(8):1274-81.

 

 

Safety

Authors: Agnes Männik, Irena Guzina, Petra Jandova, Leonor Varela Lema, Gerardo Atienza Merino

Summary

FIT and gFOBT are non-invasive tests and therefore no direct harms are expected. Indirect harms can be caused by a wrong or delayed diagnosis or by harms related to subsequent colonoscopy. Eventually, psychological impact of the screening (including psychological consequences of false-positive and false-negative test results) and patient discomfort related to the procedures must be considered.The overall number of adverse events depends on sensitivity and specificity of the  screening tests.

Subsequent colonoscopies may cause following complications – perforations of the colon, bleeding, infections, pain and discomfort. The false-positive test results may cause anxiety and distress, overdiagnosis and overtreatment. The false-negative test results may delay the detection of illness and the start of treatment.

The onset of harms (both psychological and from subsequent colonoscopies) may be immediate or delayed.

There is no evidence that there are susceptible patient groups that are more likely to be harmed through use of FIT. However, patients with comorbidities can be under higher risk with follow-up colonoscopy.

There are some organisational factors, which can affect the harms. The false-positive test results from gFOBT can be reduced by following dietary and medication restrictions. The FIT samples should be kept in refridgerator and cooling bags should be used when sending samples to clinic.

The risk of false-positive and false-negative test results might be increased if the laboratory personnel is unexperienced (risks of inaccurate interpretation of results). Complications from colonoscopy also may depend on the education and experience of health professional.

Introduction

The safety domain describes unwanted or harmful effects from FIT and gFOBT. As colonoscopy is directly connected to FIT and gFOBT, the unwanted effects from colonoscopy are also described. Indirect harms specific to colorectal cancer screening in vitro are false-positive and false-negative test results, which may cause anxiety and stress, and lead to unnecessary further investigations (eg colonoscopy, which can cause harm in turn) or may cause delay in detection of the illness. 

Methodology

Frame

A modified collection scope is used in this domain.

TechnologyFecal Immunochemical Test (FIT) for colorectal cancer screening
Description (modified from collection scope)

In CRC screening colonoscopy, that is invasive procedure, is used after positive FIT or gFOBT for approving or disapproving the occult blood test result. In that context colonoscopy is directly connected with using FIT or gFOBT and the harms related with colonoscopy are included in the analysis.

Intended use of the technology (modified from collection scope)Screening

Colonoscopy is considered as gold standard for detecting lesions and colorectal cancer.

Target condition
Adenomas, as non-malignant precursor lesions of ColoRectal Cancer (CRC).
Target condition description

CRC is the third most common in incidence and the fourth most common cause of cancer death worldwide. CRC is particularly suitable for screening. The disease is believed to develop in a vast majority of cases from non-malignant precursor lesions called adenomas. Adenomas can occur anywhere in the colorectum after a series of mutations that cause neoplasia of the epithelium. At some time , the adenoma may invade the submucosa and become malignant. Initially, this malignant cancer is not diagnosed and does not give symptoms  (preclinical phase). It can progress from localised (stage I) to metastasised (stage IV) cancer, until it causes symptoms and is diagnosed. Only 5–6% of the population actually develop CRC. The average duration of the development of an adenoma to CRC is estimated to be  at least 10 years. This long latent phase provides a window of opportunity for early detection of the disease.

Target population

Target population sex: Any. Target population age: adults and elderly. Target population group: Healthy and/or asymptomatic people.

Target population description

Adults, average risk of CRC, aged 50 years or over.

The best age range for offering gFOBT or FIT screening has not been investigated in trials. Circumstantial evidence suggests that mortality reduction from gFOBT is similar in different age ranges between 45 and 80 years .The age range for a national screening programme should at least include people aged 60 to 64 years in which CRC incidence and mortality are high and life-expectancy is still considerable. Only the FOBT for men and women aged 50–74 years has been recommended todate by the EU (Council Recommendation and the European guidelines for quality assurance in CRC screening and diagnosis).

Members of families with hereditary syndromes, previous diagnosis of CRC or pre-malignant lesions should follow specific surveillance protocols and are not included in the target population

ComparisonCRC screening with Guaiac –based fecal occult blood test (gFOBT)
Description (modified from collection scope)

The psychological harms from false-positive or false-negative test results are most likely not different using FIT or gFOBT. Thus psychological harms are described without comparison.

While gold standard for approving FIT or gFOBT results is colonoscopy, number of other diagnostic methods are available and are considered as comparisons if relevant. The alternative methods are - flexible sigmoidoscopy, computer tomography (CT), barium enema.

Outcomes

CUR and TEC

  • Health problems (target condition)
  • Epidemiology
  • Burden of disease
  • Target population
  • Current management of the condition
  • Features of the technology
  • Life-Cycle
  • Regulatory status
  • Utilization
  • Investments and tools required to use the technology
  • Training and information needed to use the technology

SAF

  • Colonoscopy probability of perforation
  • Colonoscopy with polypectomy probability of perforation
  • Colonoscopy probability of death following perforation
  • Probability of bleeding following colonoscopy
  • Psychological harms from false-negatives and false-positives (and generally from participating in screening program)

EFF

  • Test (FIT and gFOBT) sensitivity for adenomas
  • Test (FIT and gFOBT) sensitivity for cancer
  • Test (FIT and gFOBT) specificity for adenomas
  • Test (FIT and gFOBT) specificity for cancer 
  • Adenoma incidence (detection rates)
  • Rectal cancer incidence (detection rates)
  • Colon cancer incidence (detection rates)
  • CRC incidence (detection rates)
  • Stage distribution of detected cancers
  • Rectal cancer specific mortality
  • CRC specific mortality
  • Overall mortality
  • Life years saved

ECO:

  • Model/template for  national pilots  to assess the costs and benefits of the two alternative  technologies FIT and gFOBT  and also no-programmed-screening
  • Systematic literature search of   available models and/or economic  evaluation for screening colorectal cancer with FIT and gFOBT and no screening programme
  • Resource Utilization: Publicly funded health care payer costs (screening tests, further examinations e.g. labor, colonoscopy  and treatments and administration and organisation costs of screening programme) for FIT and gFOBT (in cooperation with ORG)
  • Cost per Case detected (average, marginal, incremental) =  intermediate outcome – optional, not decided yet (relevant for deciding how often a test should be carried out and what are the incremental costs for a “new” detected case
  • Indirect Costs: not for the Core modell (should be decided later on)
  • Test accuracy: from SAF
  • Cost effectiveness analysis: HRQoL measures (both generic and context specific) (EFF and SAF for help, own Lit.research), ICER

 ORG:

  • Responsiveness of target population to invitation
  • Invitation-reminder system
  • Competence of human resources – health professionals
  • Investments needed (material,equipment)
  • Costs of using both tests (FIT, gFOBT)
  • Timeliness of results and future phases
  • Use of tools for process monitoring (completed check lists)
  • Model for Budget Impact Analysis from perspective of the payer

SOC

  • Compliance with the tests (FIT, gFOBT)
  • Anxiety and any psychological effects of using  one test or another
  • Information, counseling, communication (quality of) for the use of tests
  • Satisfaction  
  • Quality of life
  • Equity of access

LEG

  • Information as baseline for an informed consent
  • Harms or inequities that can be taken to court

Assessment elements

TopicIssue RelevantResearch questions or rationale for irrelevance
C0001Patient safetyWhat kind of harms can use of the technology cause to the patient; what are the incidence, severity and duration of harms?yesWhat kind of harms can use of FIT cause to the patient; what are the incidence, severity and duration of harms?
C0002Patient safetyWhat is the dose relatedness of the harms to patients?yesWhat is the dose relatedness of the harms to patients?
C0003Patient safetyWhat is the timing of onset of harms to patients: immediate, early or late?yesWhat is the timing of onset of harms to patients: immediate, early or late?
C0004Patient safetyIs the incidence of the harms to patients likely to change over time?yesIs the incidence of the harms to patients likely to change over time?
C0005Patient safetyAre there susceptible patient groups that are more likely to be harmed through use of the technology?yesAre there susceptible patient groups that are more likely to be harmed through use of FIT?
C0006Patient safetyWhat are the consequences of false positive, false negative and incidental findings brought about using the technology to the patients from the viewpoint of patient safety?yesWhat are the consequences of false positive, false negative and incidental findings brought about using FIT to the patients from the viewpoint of patient safety?
C0007Patient safetyWhat are the special features in using (applying/interpreting/maintaining) the technology that may increase the risk of harmful events?yesWhat are the special features in using (applying/interpreting/maintaining) FIT that may increase the risk of harmful events?
C0008Patient safetyWhat is the safety of the technology in comparison to alternative technologies used for the same purpose?yesWhat is the safety of FIT in comparison to alternative technologies used for the same purpose?
C0029Patient safetyDoes the existence of harms influence tolerability or acceptability of the technology?yesDoes the existence of harms influence tolerability or acceptability of FIT?
C0020Occupational safetyWhat kind of occupational harms can occur when using the technology?yesWhat kind of occupational harms can occur when using FIT?
C0040Environmental safetyWhat kind of risks for public and environment may occur when using the technology?yesWhat kind of risks for public and environment may occur when using FIT?
C0061Safety risk managementIs there evidence that harms increase or decrease in different organizational settings?yesIs there evidence that harms increase or decrease in different organizational settings?
C0062Safety risk managementHow can one reduce safety risks for patients (including technology-, user-, and patient-dependent aspects)?yesHow can one reduce safety risks for patients (including technology-, user-, and patient-dependent aspects)?
C0063Safety risk managementHow can one reduce safety risks for professionals (including technology-, user-, and patient-dependent aspects)?yesHow can one reduce safety risks for professionals (including technology-, user-, and patient-dependent aspects)?
C0060Safety risk managementHow does the safety profile of the technology vary between different generations, approved versions or products?noIrrelevant in the context of outcomes stated in project description (colonoscopy has probably not changed over the past years and psychological harms from false-positives and false-negatives are the same no matter what test is used)
C0064Safety risk managementHow can one reduce safety risks for environment (including technology-, user-, and patient-dependent aspects)?noWill be discussed already under Issue C0040

Methodology description

Technology description:

In CRC screening, colonoscopy, that is invasive procedure, is used independently or after positive FIT or gFOBT for confirming or rejecting the occult blood test result. In that context colonoscopy is directly connected with using FIT or gFOBT and the harms related with colonoscopy are included in the analysis.

Use of technology:

Colonoscopy is considered as gold standard for detecting colon lesions and colorectal cancer.

Comparison:

The psychological harms from false-positive or false-negative test results are most likely not different using FIT or gFOBT. Thus psychological harms are described together.

While gold standard for approving FIT or gFOBT results is colonoscopy, number of other screening methods are available and are considered as comparators if relevant. The alternative methods are - flexible sigmoidoscopy, video capsule, computer tomography (CT), barium enema imaging.

Information sources

The domain literature search was used as the main information source. Also the studies from HAS (Haute Autorité de Santé) reports dated 2008 {2} and 2013 {1} were used. Relevant Cochrane systematic reviews were used. Additional searches were done through the Internet engine Google, where guidelines, reports and some free articles/studies on Oxford journals, PubMed etc. were found.

Quality assessment tools or criteria

None.

Analysis and synthesis

Different information sources were used to answer domain questions.

Result cards

Patient safety

Result card for SAF1: "What kind of harms can use of FIT cause to the patient; what are the incidence, severity and duration of harms?"

View full card
SAF1: What kind of harms can use of FIT cause to the patient; what are the incidence, severity and duration of harms?
Method
Result
Comment

Importance: Critical

Transferability: Completely

Result card for SAF2: "What is the dose relatedness of the harms to patients?"

View full card
SAF2: What is the dose relatedness of the harms to patients?
Method
Frame
Result
Comment

Importance: Unspecified

Transferability: Unspecified

Result card for SAF3: "What is the timing of onset of harms to patients: immediate, early or late?"

View full card
SAF3: What is the timing of onset of harms to patients: immediate, early or late?
Method
Result
Comment

Importance: Important

Transferability: Completely

Result card for SAF4: "Is the incidence of the harms to patients likely to change over time?"

View full card
SAF4: Is the incidence of the harms to patients likely to change over time?
Method
Result
Comment

Importance: Important

Transferability: Partially

Result card for SAF5: "Are there susceptible patient groups that are more likely to be harmed through use of FIT?"

View full card
SAF5: Are there susceptible patient groups that are more likely to be harmed through use of FIT?
Method
Result
Comment

Importance: Critical

Transferability: Completely

Result card for SAF6: "What are the consequences of false positive, false negative and incidental findings brought about using FIT to the patients from the viewpoint of patient safety?"

View full card
SAF6: What are the consequences of false positive, false negative and incidental findings brought about using FIT to the patients from the viewpoint of patient safety?
Method
Result
Comment

Importance: Important

Transferability: Completely

Result card for SAF7: "What are the special features in using (applying/interpreting/maintaining) FIT that may increase the risk of harmful events?"

View full card
SAF7: What are the special features in using (applying/interpreting/maintaining) FIT that may increase the risk of harmful events?
Method
Result
Comment

Importance: Important

Transferability: Completely

Result card for SAF8: "What is the safety of FIT in comparison to alternative technologies used for the same purpose?"

View full card
SAF8: What is the safety of FIT in comparison to alternative technologies used for the same purpose?
Method
Result

Importance: Important

Transferability: Completely

Result card for SAF10: "Does the existence of harms influence tolerability or acceptability of FIT?"

View full card
SAF10: Does the existence of harms influence tolerability or acceptability of FIT?
Method
Result
Comment

Importance: Important

Transferability: Partially

Occupational safety

Result card for SAF9: "What kind of occupational harms can occur when using FIT?"

View full card
SAF9: What kind of occupational harms can occur when using FIT?
Method
Result

Importance: Important

Transferability: Completely

Environmental safety

Result card for SAF11: "What kind of risks for public and environment may occur when using FIT?"

View full card
SAF11: What kind of risks for public and environment may occur when using FIT?
Method
Result

Importance: Important

Transferability: Completely

Safety risk management

Result card for SAF12: "Is there evidence that harms increase or decrease in different organizational settings?"

View full card
SAF12: Is there evidence that harms increase or decrease in different organizational settings?
Method
Result

Importance: Important

Transferability: Completely

Result card for SAF13: "How can one reduce safety risks for patients (including technology-, user-, and patient-dependent aspects)?"

View full card
SAF13: How can one reduce safety risks for patients (including technology-, user-, and patient-dependent aspects)?
Method
Result

Importance: Important

Transferability: Completely

Result card for SAF14: "How can one reduce safety risks for professionals (including technology-, user-, and patient-dependent aspects)?"

View full card
SAF14: How can one reduce safety risks for professionals (including technology-, user-, and patient-dependent aspects)?
Method
Result

Importance: Optional

Transferability: Completely

Discussion

There are no direct harms caused by either gFOBT or FIT.

Indirect harms can be caused by a wrong or delayed diagnosis or by harms related to subsequent colonoscopy. The total number of adverse events depends on the specificity and sensitivity of the tests and therefore may be different between gFOBT and FIT.  

There was limited evidence on different safety issues. Besides, study differences  (different populations, different study designs, different approaches in calculating the % of complications) made the interpretation and synthesis of the results difficult. 

References

  1. HAS recommendation on colorectal screening and prevention 2013 http://www.has-sante.fr/portail/upload/docs/application/pdf/2013-08/referentieleps_format2clic_kc_colon-vfinale_2013-08-30_vf_mel_2013-08-30_12-18-6_653.pdf
  2. iIFOBT in the program of organized CRC screening in France, HAS 2008 http://www.has-sante.fr/portail/upload/docs/application/pdf/2008-12/rapport_-_place_des_tests_immunologiques_de_recherche_de_sang_occulte_dans_les_selles_ifobt.pdf
  3. Hewitson P, Glasziou P, Irwig L, Towler B, Watson E. Screening for colorectal cancer using the faecal occult blood test, Hemoccult. Cochrane Database Syst Rev 2007;1
  4. Medical Services Advisory Committee. Faecal occult blood testing for population health screening. Reference 18 Assessment Report ed. Canberra: MSAC [www.msac.gov.au]; 2004.
  5. Senore, C., et al. (2011). "Acceptability and side-effects of colonoscopy and sigmoidoscopy in a screening setting." J Med Screen 18(3): 128-134
  6. Quintero, E., et al. (2012). "Colonoscopy versus fecal immunochemical testing in colorectal-cancer screening." N Engl J Med 366(8): 697-706.
  7. Guittet, L., et al. (2007). "Comparison of a guaiac based and an immunochemical faecal occult blood test in screening for colorectal cancer in a general average risk population." Gut 56(2): 210-214.
  8. NHS Centre for Reviews and Dissemination. Diagnostic accuracy and cost-effectiveness of faecal occult blood tests used in screening for colorectal cancer: a systematic review. CRD Report 36. York: 2007.
  9. Kapidzic, A., et al. (2012). "Quality of life in participants of a CRC screening program." Br J Cancer 107(8): 1295-1301.
  10. Birkenfeld, S., R. G. Belfer, et al. (2011). "Factors affecting compliance in faecal occult blood testing: a cluster randomized study of the faecal immunochemical test versus the guaiac faecal occult test." J Med Screen 18(3): 135-141.
  11. Harden, E., A. Moore, et al. (2011). "Exploring perceptions of colorectal cancer and fecal immunochemical testing among African Americans in a North Carolina community." Prev Chronic Dis 8(6): A134.
  12. Hol, L., V. de Jonge, et al. (2010). "Screening for colorectal cancer: comparison of perceived test burden of guaiac-based faecal occult blood test, faecal immunochemical test and flexible sigmoidoscopy." Eur J Cancer 46(11): 2059-2066.
  13. Hughes, K., B. Leggett, et al. (2005). "Guaic versus immunochemical tests: faecal occult blood test screening for colorectal cancer in a rural community." Aust N Z J Public Health 29: 358-364.
  14. Wong, M. C., G. K. John, et al. (2012). "Changes in the choice of colorectal cancer screening tests in primary care settings from 7,845 prospectively collected surveys." Cancer Causes Control 23(9): 1541-1548.
  15. Wong, M. C., K. K. Tsoi, et al. (2010). "A comparison of the acceptance of immunochemical faecal occult blood test and colonoscopy in colorectal cancer screening: a prospective study among Chinese." Aliment Pharmacol Ther 32(1): 74-82.
  16. Levin TR, Connell C, Shapiro JA, Chazan SG, Nadel MR, Selby JV (2002). Complications of screening flexible sigmoidoscopy. Gastroenterology 123: 1786-1792.
  17. Broadstock, M. Computed tomographic (CT) colonography for the detection of colorectal cancer – a Technical Brief. NZHTA Technical Brief 2007; 6(6)

Appendices

None.

Clinical Effectiveness

Authors: Jesús González-Enríquez, Francesca Gillespie, Stefania Lopatriello, Iñaki Imaz

Summary

The main objective of this EEF domain is to facilitate summarized information on the effectiveness of the use of Fecal Immunochemical Test (FIT) for detection of occult blood in the stool associated with colorectal lesions (adenomas and CRC), under conditions of population based colorectal cancer screening, comparing with CRC screening with Guaiac –based fecal occult blood test (gFOBT).

We have not identified any study that compares FIT vs gFOBT in terms of mortality. The identified studies that provided mortality information compared screening using FIT vs no screening and reported only colorectal cancer specific mortality. A randomised controlled trial and three observational studies examined the effect of the use of FIT for colorectal cancer screening versus no screening on colorectal cancer mortality, showing a reduction on CRC mortality. The randomised controlled trial obtained no significant differences for colorectal and colon cancer mortality, but significant for rectal cancer mortality, when compared those FIT based screened vs. those no screened In addition, three Japanese observational studies with high risk of bias found a significant reduction in CRC mortality. Therefore no direct evidence comparing FIT vs gFOBT in the context of a population based colorectal cancer screening program is available.

A high-quality level systematic review studying differences in detection rates between FIT and GFOBT has been identified {10}. This systematic review selected five randomized controlled trials comparing detection rate of advanced neoplasm of FIT vs GFOBT for screening of CRC. The five trials were combined in a meta-analysis using random effects. Colonoscopy was the reference standard. The Pooled detection rates intended to screen cancers and significant adenomas were achieved in 2.23% of individuals with FIT and 1.24% of individuals with GFOBT. The pooled Odds Ratio of detection with FIT vs. with GFOBT was 1.50 (IC 95%: 0.94-2.39). Hence, the FIT have a 50%, but not significant, higher detection rate in comparison with gFOBT for advanced adenomas and cancer.

We identified 5 systematic reviews {10,15,16,17,18} and 3 additional diagnostic cohort trials{19,20,21} directly comparing FIT vs gFOBT. Overall 6 out of the 8 studies in the table conclude that FIT is more accurate and preferable to gFOBT for CRC screening.

The most recent and high quality review {15} analyses the performance characteristics of FIT compared with gFOBT, including two randomized control trials {11,12} and two observational studies {13,14}. In summary, the sensitivity of FIT for detecting CRC and AA compared with a standard gFOBT is superior. In the two randomized control trials, specificity was decreased for CRC and Advanced Adenoma when using FIT compared with gFOBT. On the other hand, these two studies reported higher advanced neoplasia detection rates for FIT compared with gFOBT. The PPV for detecting CRC and Advanced Adenoma using FIT is not different from the standard gFOBT. In general, the positivity rates for FIT using the manufacturer’s standard cut-off level in hemoglobin concentration are higher than for gFOBT.

Overall, FIT performance is superior to the standard gFOBT for the detection of CRC and advanced adenomas in a population based screening setting. 

Introduction

The Effectiveness domain in the Core HTA considers all relevant questions related to the efficacy and effectiveness of the technology, focusing in the assessment of the health benefits. We primarily consider patient relevant outcomes (mortality, morbidity, quality of life) and performance characteristics of the intervention (accuracy). Also have considered for assessment other related effects of the intervention (change in management).

We selected the relevant Assessment elements and they were translated into research questions. The assessment elements questions for EFF Domain were selected and adapted using as a model the Core Model for Screening Technologies.

The main objective of this EEF domain is to facilitate summarized information on the effectiveness of the use of Fecal Immunochemical Test (FIT) for detection of occult blood in the stool associated with colorectal lesions (adenomas and colorectal cancer-CRC), under conditions of population based colorectal cancer screening, comparing with CRC screening with Guaiac –based fecal occult blood test (gFOBT).

 

Relevant issues and research questions selected

 

Mortality

D0001. What is the effect of FIT versus gFOBT for CRC screening on overall mortality?

D0002. What is the effect of FIT versus gFOBT for CRC screening on the mortality caused by CRC?

D0003. What is the effect of FIT versus gFOBT for CRC screening due to other causes than CRC?

Morbidity

D0005. How does the use of FIT versus gFOBT for CRC screening modify the symptoms and findings of adenomas and CRC?

D0006. How does FIT versus gFOBT for CRC screening modify the progression of adenomas and CRC?

D0026. How does the use of FIT versus gFOBT for CRC screening technology modify the effectiveness of subsequent interventions?

Change in management

D0020. Does use of FIT versus gFOBT for CRC screening lead to improved detection of adenomas and CRC?

D0022. Does FIT for CRC screening detect other potential health conditions that can impact the subsequent management decisions?

D0023.How does FIT versus gFOBT for CRC screening modifies the need for other technologies and use of resources?

Test accuracy

D1001. What is the accuracy of FIT for CRC screening against reference standard?

D1002. How does FIT compare to gFOBT for CRC screening in terms of accuracy measures?

D1003. What is the reference standard and how likely does it classify adenoma and CRC correctly?

D1005. What is the optimal threshold value of FIT for CRC screening?

D1006. Does FIT for CRC screening reliably rule in or rule out adenomas and CRC?

D1007. How does FIT accuracy vary in different settings?

D1008. What is known about the intra- and inter-observer variation in FIT interpretation?

Methodology

Frame

The collection scope is used in this domain.

TechnologyFecal Immunochemical Test (FIT) for colorectal cancer screening
Description

FITs use an antibody (immunoglobulin) specific to human globin, the protein component of haemoglobin, to detect fecal occult blood. Immunochemical tests have improved test characteristics compared to conventional guaiac-based tests for fecal occult blood. FIT should not be subject to interference from dietary blood and it is more specific to bleeding from the distal gastrointestinal tract. They could be analytically and clinically more sensitive and specific, Their measurement can be automated and the user can adjust the concentration at which a positive result is reported. A wide range of qualitative and quantitative tests is presently available, with varying levels of sensitivity and specificity (like Hem-SP/MagStream H, Fujirebio Inc. Japan ; OC-Sensor, Eiken Chemical Co., Tokyo, Japan;    FOB Gold, Medinostics Products Supplier; Sentinel Diagnostics SpA, Milan, Italy).

Intended use of the technologyScreening

CRC screening with faecal inmunochemical test (FIT) for detection of occult blood in the stool associated with colorectal lesions (adenomas and CRC).

The use of the test is considered under conditions of population based colorectal cancer screening, in the context of organised cancer screening programmes as recommended by the EU. Early detection and treatment of colorectal lesions before they become symptomatic has the potential to improve control of the disease, reducing morbidity and mortality associated to CRC. Early treatment of invasive lesions can be generally less detrimental for quality of life. The endoscopic removal of pre-malignant lesions also reduces the incidence of CRC by stopping the progression to cancer. Colorectal cancers and adenomatous polyps bleed has providing fecal blood haemoglobin as the biomarker of choice for current screening programmes. Stool samples could be periodically taken and analyzed for the presence of occult blood, as an early sign of colorectal lesions (adenoma or CRC).

Target condition
Adenomas, as non-malignant precursor lesions of ColoRectal Cancer (CRC).
Target condition description

CRC is the third most common in incidence and the fourth most common cause of cancer death worldwide. CRC is particularly suitable for screening. The disease is believed to develop in a vast majority of cases from non-malignant precursor lesions called adenomas. Adenomas can occur anywhere in the colorectum after a series of mutations that cause neoplasia of the epithelium. At some time , the adenoma may invade the submucosa and become malignant. Initially, this malignant cancer is not diagnosed and does not give symptoms  (preclinical phase). It can progress from localised (stage I) to metastasised (stage IV) cancer, until it causes symptoms and is diagnosed. Only 5–6% of the population actually develop CRC. The average duration of the development of an adenoma to CRC is estimated to be  at least 10 years. This long latent phase provides a window of opportunity for early detection of the disease.

Target population

Target population sex: Any. Target population age: adults and elderly. Target population group: Healthy and/or asymptomatic people.

Target population description

Adults, average risk of CRC, aged 50 years or over.

The best age range for offering gFOBT or FIT screening has not been investigated in trials. Circumstantial evidence suggests that mortality reduction from gFOBT is similar in different age ranges between 45 and 80 years .The age range for a national screening programme should at least include people aged 60 to 64 years in which CRC incidence and mortality are high and life-expectancy is still considerable. Only the FOBT for men and women aged 50–74 years has been recommended todate by the EU (Council Recommendation and the European guidelines for quality assurance in CRC screening and diagnosis).

Members of families with hereditary syndromes, previous diagnosis of CRC or pre-malignant lesions should follow specific surveillance protocols and are not included in the target population

ComparisonCRC screening with Guaiac –based fecal occult blood test (gFOBT)
Description

CRC screening with Guaiac–based fecal occult blood test (gFOBT)

The guaiac-based FOBT is still a commonly used method for detecting blood in faeces. To detect hemoglobin the test uses guaiac gum and its efficacy as a colorectal cancer screening test has been analyzed in several randomised controlled trials. The test detects the haem component of haemoglobin, which is identical across human and animal species and is chemically robust and only partially degraded during its passage through the gastrointestinal tract. gFOBTs cannot distinguish between human blood and blood residues from the diet.

Many guaiac-based tests are currently on the market (like Coloscreen, Helena Laboratories,Texas,USA; Hema-screen Immunostics Inc.; Hemoccult, Beckman Coulter Inc.; Hemoccult SENSA, Beckman Coulter Inc.; MonoHaem, Chemicon Europe Ltd; Hema-Check, Siemens PLC; HemaWipe, Medtek Diagnostics LLC)

The use of the test is considered under conditions of population based colorectal cancer screening, in the context of organised cancer screening programmes as recommended by the EU. Population-based programmes have been rolled out nationwide in several European countries. Many member states  haveestablished nationwide non-population-based programmes. Some states are planning or piloting a nationwide population-based programme. These have  adopted only FOBT, some only FIT, some a mix between FOBT and endoscopy, or only colonoscopy.

Outcomes

CUR and TEC

  • Health problems (target condition)
  • Epidemiology
  • Burden of disease
  • Target population
  • Current management of the condition
  • Features of the technology
  • Life-Cycle
  • Regulatory status
  • Utilization
  • Investments and tools required to use the technology
  • Training and information needed to use the technology

SAF

  • Colonoscopy probability of perforation
  • Colonoscopy with polypectomy probability of perforation
  • Colonoscopy probability of death following perforation
  • Probability of bleeding following colonoscopy
  • Psychological harms from false-negatives and false-positives (and generally from participating in screening program)

EFF

  • Test (FIT and gFOBT) sensitivity for adenomas
  • Test (FIT and gFOBT) sensitivity for cancer
  • Test (FIT and gFOBT) specificity for adenomas
  • Test (FIT and gFOBT) specificity for cancer 
  • Adenoma incidence (detection rates)
  • Rectal cancer incidence (detection rates)
  • Colon cancer incidence (detection rates)
  • CRC incidence (detection rates)
  • Stage distribution of detected cancers
  • Rectal cancer specific mortality
  • CRC specific mortality
  • Overall mortality
  • Life years saved

ECO:

  • Model/template for  national pilots  to assess the costs and benefits of the two alternative  technologies FIT and gFOBT  and also no-programmed-screening
  • Systematic literature search of   available models and/or economic  evaluation for screening colorectal cancer with FIT and gFOBT and no screening programme
  • Resource Utilization: Publicly funded health care payer costs (screening tests, further examinations e.g. labor, colonoscopy  and treatments and administration and organisation costs of screening programme) for FIT and gFOBT (in cooperation with ORG)
  • Cost per Case detected (average, marginal, incremental) =  intermediate outcome – optional, not decided yet (relevant for deciding how often a test should be carried out and what are the incremental costs for a “new” detected case
  • Indirect Costs: not for the Core modell (should be decided later on)
  • Test accuracy: from SAF
  • Cost effectiveness analysis: HRQoL measures (both generic and context specific) (EFF and SAF for help, own Lit.research), ICER

 ORG:

  • Responsiveness of target population to invitation
  • Invitation-reminder system
  • Competence of human resources – health professionals
  • Investments needed (material,equipment)
  • Costs of using both tests (FIT, gFOBT)
  • Timeliness of results and future phases
  • Use of tools for process monitoring (completed check lists)
  • Model for Budget Impact Analysis from perspective of the payer

SOC

  • Compliance with the tests (FIT, gFOBT)
  • Anxiety and any psychological effects of using  one test or another
  • Information, counseling, communication (quality of) for the use of tests
  • Satisfaction  
  • Quality of life
  • Equity of access

LEG

  • Information as baseline for an informed consent
  • Harms or inequities that can be taken to court

Assessment elements

TopicIssue RelevantResearch questions or rationale for irrelevance
D0001MortalityWhat is the effect of the intervention on overall mortality?yesWhat is the effect of FIT versus gFOBT for CRC screening on overall mortality?
D0002MortalityWhat is the effect of the intervention on the mortality caused by the target disease?yesWhat is the effect of FIT versus gFOBT for CRC screening on the mortality caused by CRC?
D0003MortalityWhat is the effect of the intervention on the mortality due to other causes than the target disease?yesWhat is the effect of FIT versus gFOBT for CRC screening on the mortality due to other causes than CRC?
D0004MortalityWhat is the mortality related to the diagnostic test?noThere is no mortality directly associated to FIT or gFOBT
D0005MorbidityHow does the use of the technology modify the symptoms and findings of the target condition?yesHow does the use of FIT for CRC screening modify the symptoms and findings of adenomas and CRC?
D0006MorbidityHow does the technology modify the progression of the target condition?yesHow does FIT for CRC screening modify the progression of adenomas and CRC?
D0026MorbidityHow does the technology modify the effectiveness of subsequent interventions?yesHow does the use of FIT versus gFOBT for CRC screening technology modify the effectiveness of subsequent interventions?
D0008MorbidityWhat is the morbidity directly related to the technology?noThere is no morbidity directly related to FIT or gFOBT.
D0020Change-in managementDoes use of the test lead to improved detection of the condition?yesDoes use of FIT versus FOBT for CRC screening lead to improved detection of adenomas and CRC?
D0022Change-in managementDoes the test detect other potential health conditions that can impact the subsequent management decisions?yesDoes FIT for CRC screening detect other potential health conditions that can impact the subsequent management decisions?
D0023Change-in managementHow does the technology modify the need for other technologies and use of resources?yesHow does FIT versus FOBT for CRC screening modify the need for other technologies and use of resources?
D0021Change-in managementHow does the use of the test change physicians' management decisions?noA positive test must be folowed of new invasive tests for diagnosis (colonoscopy). It is not expected that the use of FIT vs gFOBT change the physician’s management decisions. The strategy of performing new invasive diagnostic tests (colonoscopy) following a positive result that is accepted for gFOBT should be applied for FIT.
D0024Change-in managementIs there an effective treatment for the condition the test is detecting?noThere is no a need of key information regarding this question for the specific framing of this CORE HTA. There are clear evidences regarding treatment effectiveness for CRC and adenomas, and this ussue would not affect in a relevant way our specific scope.
D1001Test accuracyWhat is the accuracy of the test against reference standard?yesWhat is the accuracy of FIT for CRC screening against reference standard?
D1002Test accuracyHow does the test compare to other optional tests in terms of accuracy measures?yesHow does FIT compare to gFOBT for CRC screening in terms of accuracy measures?
D1003Test accuracyWhat is the reference standard and how likely does it classify the target condition correctly?yesWhat is the reference standard and how likely does it classify adenoma and CRC correctly?
D1005Test accuracyWhat is the optimal threshold value in this context?yesWhat is the optimal threshold value of FIT for CRC screening?
D1006Test accuracyDoes the test reliably rule in or rule out the target condition?yesDoes FIT for CRC screening reliably rule in or rule out adenomas and CRC?
D1007Test accuracyHow does test accuracy vary in different settings?yesHow does FIT accuracy vary in different settings?
D1008Test accuracyWhat is known about the intra- and inter-observer variation in test interpretation?yesWhat is known about the intra- and inter-observer variation in FIT interpretation?
D1004Test accuracyWhat are the requirements for accuracy in the context the technology will be used?noAlready included within the question G0012 of the ORG domain which is related to quality standards.
D1019Test accuracyIs there evidence that the replacing test is more specific or safer than the old one?noRegarding specificity, it is already included in the effectiveness domain question D1002. Regarding safety, it is already included within SAF domain.
D0027Test accuracyWhat are the negative consequences of further testing and delayed treatment in patients with false negative test result?noConsidered as a relevant question more specifically related to SAF domain (C006)
D0028Test accuracyWhat are the negative consequences of further testing and treatments in patients with false positive test result?noConsidered as a relevant question more specifically related to SAF domain (C006)
D0011FunctionWhat is the effect of the intervention on global function?noAlready included as a relevant outcome within SOC domain
D0014FunctionWhat is the effect of the technology on return to work?noAlready included as a relevant outcome within SOC domain
D0015FunctionWhat is the effect of the technology on return to previous living conditions?noAlready included as a relevant outcome within SOC domain
D0016FunctionHow does use of the technology affect activities of daily living?noAlready included as a relevant outcome within SOC domain
D0012Quality of lifeWhat is the effect of the technology on generic health-related quality of life?noAlready included as a relevant outcome within SOC domain
D0013Quality of lifeWhat is the effect of the technology on disease specific quality of life?noAlready included as a relevant outcome within SOC domain
D0030Quality of lifeDoes the knowledge of the test result affect the patient's non-health-related quality of life?noAlready included as a relevant outcome within SOC domain
D0017Patient satisfactionWas the use of the technology worthwhile?noAlready included as a relevant outcome within SOC domain (Patient satisfaction, global value)
D0018Patient satisfactionIs the patient willing to use the technology?noAlready included as a relevant outcome within SOC and ORG domains (Patient satisfaction, acceptance)
D0029Benefit-harm balanceWhat are the overall benefits and harms of the technology in health outcomes?noThis is a question to be answered with all the information available from all domains. It requires a comprehensive assessment of the overall value of the intervention.

Methodology description

Domain frame/PICO

The project scope is applied in this domain:

Technology

FIT for colorectal cancer screening vs. gFOBT colorectal cancer screening in organized screening program

Description

Procedure of gFOBT: the standard fecal occult blood (FOBT) test can detect small amounts of blood in the stool by submitting a portion of three consecutive bowel movements for testing. The test cannot identify polyps and some diet restrictions need to be considered, as the test is not specific for human blood alone. gFOBT is used for more than 30 years in routine, is widely available and inexpensive. If the test is positive, a colonoscopy will be needed to find the reason for the bleeding.

Procedure of FIT: FIT (Fecal Immunochemical Test) for colorectal cancer screening, also called as iFOBT (immunochemical FOBT) screening, is more accurate than FOBT as it only identifies human blood. It needs only one stool sample, thus is more simple to complete. If the test is positive, a colonoscopy will be needed to find the reason for the bleeding.

Colorectal cancer screening with faecal inmunochemical test (FIT) for detection of occult blood in the stool associated with colorectal lesions (adenomas and CRC) is considered under conditions of population based colorectal cancer screening, in the context of organised cancer screening programmes as recommended by the EU. Early detection and treatment of colorectal lesions before they become symptomatic has the potential to improve control of the disease, reducing morbidity and mortality associated to CRC. Early treatment of invasive lesions can be generally less detrimental for quality of life. The endoscopic removal of pre-malignant lesions also reduces the incidence of CRC by stopping the progression to cancer. Stool samples could be periodically taken and analysed for the presence of occult blood, as an early sign of colorectal lesions (adenoma or CRC).

To ensure effectiveness, the screening interval in a national screening programme should not exceed two years for gFOBT and three years for FIT.

Purpose of use: detect cancer, polyps, nonpolypoid lesions, which are flat or slightly depressed areas of abnormal cell growth and can also develop into colorectal cancer.

Intended use of the technology

Screening

CRC screening with faecal immunochemical test (FIT)

Target condition

Adenomas, as non-malignant precursor lesions of Colorectal Cancer.

Target condition description

CRC is the third most common in incidence and the fourth most common cause of cancer death worldwide. CRC is particularly suitable for screening. The disease is believed to develop in a vast majority of cases from non-malignant precursor lesions called adenomas. Adenomas can occur anywhere in the colorectum after a series of mutations that cause neoplasia of the epithelium. Adenoma may invade the submucosa and become malignant. Initially, this malignant cancer is not diagnosed and does not cause symptoms (preclinical phase). It can progress from localised (stage I) to metastasised (stage IV) cancer, until it causes symptoms and is diagnosed. Only 5–6% of the general population actually develop CRC. The average duration of the development of an adenoma to CRC is estimated to be at least 10 years. This long latent phase provides a window of opportunity for early detection of the disease.

Target population

Target population sex: any. Target population age: 50-74 years. Target population group: Asymptomatic people.

Target population description

Adults (both men and women), average risk of CRC, aged 50 years or over.

The best age range for offering gFOBT or FIT screening has not been investigated in trials. Circumstantial evidence suggests that mortality reduction from gFOBT is similar in different age ranges between 45 and 80 years. The age range for a national screening programme should at least include people aged 60 to 64 years in which CRC incidence and mortality are high and life-expectancy is still considerable. EU Council Recommendations suggests only the faecal occult blood test (gFOBT or FIT) for men and women aged 50–74 for CRC screening.

Members of families with hereditary syndromes, previous diagnosis of CRC or pre-malignant lesions should follow specific surveillance protocols and are not included in the target population.

 

Comparison

CRC screening with Guaiac – based fecal occult blood test (gFOBT)

Description

CRC screening with Guaiac–based fecal occult blood test (gFOBT)

The guaiac-based FOBT is still a commonly used method for detecting blood in faeces. To detect haemoglobin the test uses guaiac gum and its efficacy as a colorectal cancer screening test has been analysed in several randomised controlled trials. The test detects the haem component of haemoglobin, which is identical across human and animal species and is chemically robust and only partially degraded during its passage through the gastrointestinal tract. gFOBTs cannot distinguish between human blood and blood residues from the diet.

Many guaiac-based tests are currently on the market (like Coloscreen, Helena Laboratories,Texas,USA; Hema-screen Immunostics Inc.; Hemoccult, Beckman Coulter Inc.; Hemoccult SENSA, Beckman Coulter Inc.; MonoHaem, Chemicon Europe Ltd; Hema-Check, Siemens PLC; HemaWipe, Medtek Diagnostics LLC).

The use of the test is considered under conditions of population based colorectal cancer screening in the context of organised cancer screening programmes as recommended by the EU. Population-based programmes have been rolled out nationwide in several European countries. Many member states have established nationwide non-population-based programmes. Some states are planning or piloting a nationwide population-based programme. These have adopted only gFOBT, some only FIT, some a mix between FOBT and endoscopy, or only colonoscopy.

 

 

EFF domain Outcomes

  • Test (FIT and gFOBT) sensitivity for adenomas
  • Test (FIT and gFOBT) sensitivity for cancer
  • Test (FIT and gFOBT) specificity for adenomas
  • Test (FIT and gFOBT) specificity for cancer 
  • Adenoma incidence (detection rates)
  • Rectal cancer incidence (detection rates)
  • Colon cancer incidence (detection rates)
  • CRC incidence (detection rates)
  • Stage distribution of detected cancers
  • Rectal cancer specific mortality
  • CRC specific mortality
  • Overall mortality
  • Life years saved

 

Information sources

Answers to the selected research questions of the EFF domain are mainly based in systematic literature search in the following sources {EFF Appendix 1}:

  1. A basic literature search for the technology (FIT_technology) (MEDLINE, EMBASE, Cochrane Library: CDSR, DARE, HTA database, CENTRAL).

 

  1. A specific complementary EFF domain search strategy, using the following sources (MEDLINE, EMBASE, Cochrane Library, SCOPUS).

 

This specific literature search strategy was produced to answer the EEF domain research questions.

We merged the two databases, general and specific, excluding duplicates, and worked with it to answer all research questions. The final selection after deletion of duplicates included a total of 620 studies.

Additional information sources were used to answer specific research questions when the data retrieved through a systematic review did not provide adequate information (hand searching of journals and references in selected studies, trial registers and grey literature).

Retrieved articles were included or excluded according to the PICO adopted for the project scope and related directly to the outcomes selected in the EFF domain. Abstracts resulting from the literature searches were independently assessed by at least two investigators. A final database with 176 selected studies from the merger of the two search strategies used for our EFF domain, after excluding references not directly related to the EFF domain frame and research questions.

Priority was done to the identification of systematic reviews and clinical trials.

For research questions related with issues of mortality, morbidity and change in management the project approach were mainly based in prospective controlled clinical trials, meta-analysis or systematic reviews of clinical trials. Other study types and designs have been considered (observational studies, prognostic studies, registries, statistics) if adequate for some research questions.

For research questions related with test accuracy we searched for diagnostic accuracy reviews, and clinically relevant diagnostic studies comparing FIT and FOBT were selected. Inclusion criteria where: studies that report data on accuracy measures (sensitivity, specificity, positive and negative predictive values, likelihood ratios, SROC and other measures, detection rates), publication date after year 2000, FIT compared with gFOBT or alone, on asymptomatic average risk patients, age 50+ years, data on specific issues relative to selected research questions.

Relevant articles considered to meet inclusion criteria for one selected research question were fully assessed (described, data extraction table, quality assessment) by the investigators. Extraction tables where tailored to research questions issues.

 

Quality assessment tools or criteria

The quality of the selected studies was analyzed by using the Cochrane risk of bias checklist for randomized controlled trials and for non-randomized studies {1}. To evaluate the quality of systematic reviews we used the 11 items of the Revised Assessment of Multiple Systematic Reviews (R-AMSTAR){2}. Test accuracy studies included in systematic reviews and qualified with QUADAS have also been reported.

Analysis and synthesis

Priority is given to reporting summary effects measures from systematic reviews and randomized clinical trials. When quantitative pooling of results is available or possible from meta-analysis it is presented. When the heterogeneity of studies and nature of data available prevent from pooling on a summary estimate, specific data are described and reported.

Summary informative evidence tables of selected studies are presented once reviewed for methodological quality. Data was synthesized in tables were possible and research questions were answered starting from the best quality of available evidence.

Assessing the accuracy of the screening test we report summary measures from the selected systematic reviews and meta-analysis (pooled sensitivity, pooled specificity, predictive values, likelihood ratios or area under receiver operating characteristic curve), and specific results from other prospective studies once reviewed for methodological quality.

Additional descriptive analysis is presented, interpreted and commented if necessary for the EFF assessment elements. 

Result cards

Mortality

Result card for EFF2: "What is the effect of FIT versus gFOBT for CRC screening on overall mortality?"

View full card
EFF2: What is the effect of FIT versus gFOBT for CRC screening on overall mortality?
Method
Result

Importance: Important

Transferability: Completely

Result card for EFF4: "What is the effect of FIT versus gFOBT for CRC screening on the mortality caused by CRC?"

View full card
EFF4: What is the effect of FIT versus gFOBT for CRC screening on the mortality caused by CRC?
Method
Result
Comment

Importance: Important

Transferability: Completely

Result card for EFF6: "What is the effect of FIT versus gFOBT for CRC screening on the mortality due to other causes than CRC?"

View full card
EFF6: What is the effect of FIT versus gFOBT for CRC screening on the mortality due to other causes than CRC?
Method
Result

Importance: Important

Transferability: Completely

Morbidity

Result card for EFF8: "How does the use of FIT for CRC screening modify the symptoms and findings of adenomas and CRC?"

View full card
EFF8: How does the use of FIT for CRC screening modify the symptoms and findings of adenomas and CRC?
Method
Result

Importance: Optional

Transferability: Partially

Result card for EFF10: "How does FIT for CRC screening modify the progression of adenomas and CRC?"

View full card
EFF10: How does FIT for CRC screening modify the progression of adenomas and CRC?
Method
Result
Comment

Importance: Optional

Transferability: Partially

Result card for EFF18: "How does the use of FIT versus gFOBT for CRC screening technology modify the effectiveness of subsequent interventions?"

View full card
EFF18: How does the use of FIT versus gFOBT for CRC screening technology modify the effectiveness of subsequent interventions?
Method
Result

Importance: Optional

Transferability: Not

Change-in management

Result card for EFF12: "Does use of FIT versus FOBT for CRC screening lead to improved detection of adenomas and CRC?"

View full card
EFF12: Does use of FIT versus FOBT for CRC screening lead to improved detection of adenomas and CRC?
Method
Result

Importance: Critical

Transferability: Completely

Result card for EFF14: "Does FIT for CRC screening detect other potential health conditions that can impact the subsequent management decisions?"

View full card
EFF14: Does FIT for CRC screening detect other potential health conditions that can impact the subsequent management decisions?
Method
Result

Importance: Optional

Transferability: Not

Result card for EFF16: "How does FIT versus FOBT for CRC screening modify the need for other technologies and use of resources?"

View full card
EFF16: How does FIT versus FOBT for CRC screening modify the need for other technologies and use of resources?
Method
Result

Importance: Important

Transferability: Partially

Test accuracy

Result card for EFF20: "What is the accuracy of FIT for CRC screening against reference standard?"

View full card
EFF20: What is the accuracy of FIT for CRC screening against reference standard?
Method
Result

Importance: Important

Transferability: Partially

Result card for EFF22: "How does FIT compare to gFOBT for CRC screening in terms of accuracy measures?"

View full card
EFF22: How does FIT compare to gFOBT for CRC screening in terms of accuracy measures?
Method
Result
Comment

Importance: Critical

Transferability: Partially

Result card for EFF24: "What is the reference standard and how likely does it classify adenoma and CRC correctly?"

View full card
EFF24: What is the reference standard and how likely does it classify adenoma and CRC correctly?
Method
Result
Comment

Importance: Critical

Transferability: Completely

Result card for EFF26: "What is the optimal threshold value of FIT for CRC screening?"

View full card
EFF26: What is the optimal threshold value of FIT for CRC screening?
Method
Result

Importance: Important

Transferability: Completely

Result card for EFF31: "Does FIT for CRC screening reliably rule in or rule out adenomas and CRC?"

View full card
EFF31: Does FIT for CRC screening reliably rule in or rule out adenomas and CRC?
Method
Result
Comment

Importance: Important

Transferability: Partially

Result card for EFF28: "How does FIT accuracy vary in different settings?"

View full card
EFF28: How does FIT accuracy vary in different settings?
Method
Result

Importance: Important

Transferability: Completely

Result card for EFF30: "What is known about the intra- and inter-observer variation in FIT interpretation?"

View full card
EFF30: What is known about the intra- and inter-observer variation in FIT interpretation?
Method
Result

Importance: Important

Transferability: Partially

Discussion

With the evidence available for the effectiveness of FIT for CRC screening, it could be argued that it is appropriate to implement FIT instead of gFOBT without direct evidence from high quality RCT on CRC mortality, given that FIT is more sensitive for advanced adenomas and cancer, at least presents equal high specificity and higher detection rates for advanced adenomas and cancer.

Referring to test accuracy assessment, well-designed randomized controlled studies directly comparing FIT and gFOBT are needed. The use the Standards for Reporting of Diagnostic Accuracy guidelines is recommended for reporting future diagnostic accuracy studies. Studies should ideally recruit a representative screening population, use colonoscopy to confirm diagnosis regardless of the FOBT result, measure the detection of CRC and adenomas and report the results separately and combined, and allow outcome assessors access to clinical information that would be available in practice, but blind them to other information. Specimen instability issue must be considered in each setting. The type of FIT and associated costs, the appropriate haemoglobin cut-off to use, and the capacity for follow-up by colonoscopy or flexible sigmoidoscopy may contribute to the evidence of FIT as an appropriate CRC screening tool.

Despite the differences in the design and heterogeneity of selected studies the analysis shows that FIF is more accurate and performs better than gFOBT in detecting advanced adenoma and CRC.

FIT has additional important advantages compared to gFOBT: higher acceptance and screening participation rates, needs a smaller number of stool samples, has no need for dietary restriction, potential for automation in the laboratory and to select the cut-off level of hemoglobin concentration that defines a positive test. However, potential disadvantages are greater specimen instability and possibly higher positivity rates.

Global balance between total health benefits and harms and costs is out of the scope of the EFF domain. The global impact of false positive screening results and false negative screening results, the potential effects of over-diagnosis and over-treatment have not been considered. This global balance could be obtained in a comprehensive view of all pieces of information produced by all domains of the CoreHTA and could need the design of specific analytical modeling.

References

1.         Cochrane Handbook for Systematic Reviews of Interventions. The Cochrane Collaboration; 2011.

2.         Kung J, Chiappelli F, Cajulis OO, Avezova R, Kossan G, Chew L, et al. From Systematic Reviews to Clinical Recommendations for Evidence-Based Health Care: Validation of Revised Assessment of Multiple Systematic Reviews (R-AMSTAR) for Grading of Clinical Relevance. Open Dent J. 2010; 4:84-91.

3.         Zheng S, Chen K, Liu X, Ma X, Yu H, Chen K, et al. Cluster randomization trial of sequence mass screening for colorectal cancer. Dis Colon Rectum. 2003; 46(1):51-8.

4.         Wada T, Saito H, Soma Y, Koeda J, Kawaguchi H, Tanaka M, et al. Survival benefit for patients with colorectal cancer detected by population-based screening program using an immunochemical fecal occult blood test. Int J Oncol 1996; 9:685-91.

5.         Nakajima M, Saito H, Soma Y, Sobue T, Tanaka M, Munakata A. Prevention of advanced colorectal cancer by screening using the immunochemical faecal occult blood test: a case-control study. Br J Cancer 2003; 89(1):23-8.

6.         Saito H, Soma Y, Nakajima M, Koeda J, Kawaguchi H, Kakizaki R, et al. A case-control study evaluating occult blood screening for colorectal cancer with hemoccult test and an immunochemical hemagglutination test. Oncol Rep 2000;7:815-9.

7.         Saito H, Soma Y, Koeda J, Wada T, Kawaguchi H, Sobue T, et al. Reduction in risk of mortality from colorectal cancer by fecal occult blood screening with immunochemical hemagglutination test. A case-control study. Int J Cancer 1995; 61:465-9.

8.         Hewitson P, Glasziou P, Watson E, Towler B, Irwig L. Cochrane systematic review of colorectal cancer screening using the fecal occult blood test (Hemoccult): An update. Am J Gastroenterol 2008; 103(6):1541-9.

9.         Parente F, Marino B, DeVecchi N, Moretti R, Ucci G, Tricomi P, et al. Colorectal Cancer Screening Group. Faecal occult blood test-based screening programme with high compliance for colonoscopy has a strong clinical impact on colorectal cancer. Br J Surg 2009; 96(5):533-40.

10.       Zhu MM, Xu XT, Nie F, Tong JL, Xiao SD, Ran ZH. Comparison of immunochemical and guaiac-based fecal occult blood test in screening and surveillance for advanced colorectal neoplasms: A meta-analysis. J Dig Dis 2010; 11(3):148-60.

11.       Van Rossum LG, van Rijn AF, Laheij RJ, van Oijen MG, Fockens P, van Krieken HH, et al. Random Comparison of Guaiac and Immunochemical Fecal Occult Blood Tests for Colorectal Cancer in a Screening Population. Gastroenterology 2008; 135(1):82-90.

12.       Hol L, Wilschut JA, Van Ballegooijen M, van Vuuren AJ, Van Der Valk H, Reijerink JCIY, et al. Screening for colorectal cancer: Random comparison of guaiac and immunochemical faecal occult blood testing at different cut-off levels. Br J Cancer 2009; 100(7):1103-10.

13.       Park DI, Ryu S, Kim YH, Lee SH, Lee CK, Eun CS, et al. Comparison of guaiac-based and quantitative immunochemical fecal occult blood testing in a population at average risk undergoing colorectal cancer screening. Am J Gastroenterol 2010; 105(9):2017-25.

14.       Allison JE, Sakoda LC, Levin TR, Tucker JP, Tekawa IS, Cuff T, et al. Screening for colorectal neoplasms with new fecal occult blood tests: update on performance characteristics. J Natl Cancer Inst 2007; 99(19):1462-70.

15.       Rabeneck L, Rumble RB, Thompson F, Mills M, Oleschuk C, Whibley A, et al. Fecal immunochemical tests compared with guaiac fecal occult blood tests for population-based colorectal cancer screening. Can J Gastroenterol 2012; 26(3):131-47.

16.       Fecal occult blood test for colorectal cancer screening: an evidence-based analysis. Ont Heal Technol Assess Ser. 2009; 9(10):1-40.

17.       Burch JA, Soares-Weiser K, St John DJB, Duffy S, Smith S, Kleijnen J, et al. Diagnostic accuracy of faecal occult blood tests used in screening for colorectal cancer: A systematic review. J Med Screen 2007; 14(3):132-7.

18.       Fecal immunochemical tests for colorectal cancer screening: a systematic review of accuracy and compliance. CADTH Technol Overv 2010; 1(3):e0117.

19.       Faivre J, Dancourt V, Denis B, Dorval E, Piette C, Perrin P, et al. Comparison between a guaiac and three immunochemical faecal occult blood tests in screening for colorectal cancer. Eur J Cancer 2012; 48(16):2969-76.

20.       Raginel T, Puvinel J, Ferrand O, Bouvier V, Levillain R, Ruiz A, et al. A Population-based Comparison of Immunochemical Fecal Occult Blood Tests for Colorectal Cancer Screening. Gastroenterology 2013; 144: 918-925.

21.       Wong CKW, Fedorak RN, Prosser CI, Stewart ME, Van Zanten SV, Sadowski DC. The sensitivity and specificity of guaiac and immunochemical fecal occult blood tests for the detection of advanced colonic adenomas and cancer. Int J Colorectal Dis 2012; 27 (12):1657-64.

22.       Allameh Z, Davari M, Emami MH. Sensitivity and specificity of colorectal cancer mass screening methods: A systematic review of the literature. Iran J Cancer Prev 2011; 4(2):88-105.

23.       Chen LS, Yen AMF, Chiu SYH, Liao CS, Chen HH. Baseline faecal occult blood concentration as a predictor of incident colorectal neoplasia: Longitudinal follow-up of a Taiwanese population-based colorectal cancer screening cohort. Lancet Oncol 2011; 12(6):551-8.

24.       Digby J, Fraser CG, Carey FA, McDonald PJ, Strachan JA, Diament RH, et al. Faecal haemoglobin concentration is related to severity of colorectal neoplasia. J Clin Pathol 2013; 66(5): 415-419.

25.       Haug U, Hundt S, Brenner H. Quantitative immunochemical fecal occult blood testing for colorectal adenoma detection: evaluation in the target population of screening and comparison with qualitative tests. Am J Gastroenterol 2010; 105(3):682-90.

26.       Wilschut JA, Habbema JD, van Leerdam ME, Hol L, Lansdorp-Vogelaar I, Kuipers EJ, et al. Fecal occult blood testing when colonoscopy capacity is limited. J Natl Cancer Inst 2011; 103 (23):1741-51.

27.       Chiu HM, Lee YC, Tu CH, Chen CC, Tseng PH, Liang JT, et al. Association Between Early-Stage Colon Neoplasms and False-Negative Results from the Fecal Immunochemical Test. Clin Gastroenterol Hepatol 2013; 11(7):832-8.

28.       Denters MJ, Deutekom M, Bossuyt PM, Stroobants AK, Fockens P, Dekker E. Lower risk of advanced neoplasia among patients with a previous negative result from a fecal test for colorectal cancer. Gastroenterology 2012; 142(3):497-504.

29.       Cha JM, Lee JI, Joo KR, Shin HP, Park JJ, Jeun JW, et al. Performance of the fecal immunochemical test is not decreased by high ambient temperature in the rapid return system. Dig Dis Sci 2012; 57(8):2178-83.

30.       Van Rossum LGM, van Rijn AF, Van Oijen MGH, Fockens P, Laheij RJF, Verbeek ALM, et al. False negative fecal occult blood tests due to delayed sample return in colorectal cancer screening. Int J Cancer 2009; 125(4):746-50.

31.       Tannous B, Lee-Lewandrowski E, Sharples C, Brugge W, Bigatello L, Thompson T, et al. Comparison of conventional guaiac to four immunochemical methods for fecal occult blood testing: implications for clinical practice in hospital and outpatient settings. Clin Chim Acta. febrero de 2009; 400(1-2):120-2.

32.       Haug U, Kuntz KM, Knudsen AB, Hundt S, Brenner H. Sensitivity of immunochemical faecal occult blood testing for detecting left- vs  right-sided colorectal neoplasia. Br J Cancer 2011; 104(11):1779-85.

33.       Park MJ, Choi KS, Lee YK, Jun JK, Lee HY. A comparison of qualitative and quantitative fecal immunochemical tests in the Korean national colorectal cancer screening program. Scand J Gastroenterol 2012; 47(4):461-6. 

Appendices

APPENDIX 1. Search strategies and flow chart.

 

pdf10936.EFF Appendix 1

 

10936.EFF Flow Chart Appendix 1

 

APPENDIX 2. Revised Assessment of Multiple Systematic Reviews (R-AMSTAR)

 

pdf10936.EFF Appendix 2

 

 

APPENDIX 3. Evidence tables of studies, description of studies, quality assessment.

 

pdf10936.EFF Appendix 3

 

 

Costs and economic evaluation

Authors: Principal Investigators: Anna-Theresa Renner, Ingrid Rosian-Schikuta, Investigators: Nika Berlic, Neill Booth, Valentina Prevolnik Rupel

Summary

Cost-effectiveness studies generally find that both FIT and FOBT have relatively favourable ICERs when compared with no screening. Although neither type of screening modality is always more cost effective than the other, cost-effectiveness models tend to suggest FIT has more favourable ICERs. However, it should be noted that, compared to gFOBT, the added test sensitivity of FIT is accompanied by a need for a higher capacity in undertaking diagnostic colonoscopies. Therefore, there is increased up-front resource use, potential harm and cost associated with these colonoscopies which will normally be undertaken when screening using FIT (in comparison to gFOBT). FIT also lacks direct evidence from randomised trials concerning its effect on mortality. With the advent of increasingly expensive treatments, the cost-effectiveness both of FIT and gFOBT is likely to increase. On the other hand, although FIT is likely to detect more asymptomatic cancers than gFOBT, this increased test sensitivity increases diagnostic testing costs and also increases the possible dangers associated with screening-induced colonoscopy.

Introduction

Colorectal cancer (CRC) is the second most frequent malignancy in developed countries. The overall burden of disease in Europe caused by CRC is high due to both, a high incidence rate and a high mortality. Estimates show that over 450,000 people were diagnosed with, and over 223,000 died of, CRC in Europe in 2008. Hence, the number of new CRC cases was nearly 51 per 100,000 Europeans and the mortality of CRC was over 25 per 100,000 Europeans {1}. Screening and detecting adenomas or polyps in an average risk population has the potential to reduce the individual, social and financial burden of disease.

The aim of this Cost and economic evaluation domain is to summarise the results of a systematic literature search concerning the costs and cost-effectiveness of immunochemical versus guaiac-based faecal occult blood tests used for CRC screening. This is done to gain insight into the results and the study design of published cost-effectiveness models and support decision making on screening. The domain reviews published cost-effectiveness studies that include a (direct or indirect) comparison of a Faecal Immunochemical Test (FIT) and a Guaiac-based Faecal Occult Blood Test (gFOBT) {2}.

Methodology

Frame

The collection scope is used in this domain.

TechnologyFecal Immunochemical Test (FIT) for colorectal cancer screening
Description

FITs use an antibody (immunoglobulin) specific to human globin, the protein component of haemoglobin, to detect fecal occult blood. Immunochemical tests have improved test characteristics compared to conventional guaiac-based tests for fecal occult blood. FIT should not be subject to interference from dietary blood and it is more specific to bleeding from the distal gastrointestinal tract. They could be analytically and clinically more sensitive and specific, Their measurement can be automated and the user can adjust the concentration at which a positive result is reported. A wide range of qualitative and quantitative tests is presently available, with varying levels of sensitivity and specificity (like Hem-SP/MagStream H, Fujirebio Inc. Japan ; OC-Sensor, Eiken Chemical Co., Tokyo, Japan;    FOB Gold, Medinostics Products Supplier; Sentinel Diagnostics SpA, Milan, Italy).

Intended use of the technologyScreening

CRC screening with faecal inmunochemical test (FIT) for detection of occult blood in the stool associated with colorectal lesions (adenomas and CRC).

The use of the test is considered under conditions of population based colorectal cancer screening, in the context of organised cancer screening programmes as recommended by the EU. Early detection and treatment of colorectal lesions before they become symptomatic has the potential to improve control of the disease, reducing morbidity and mortality associated to CRC. Early treatment of invasive lesions can be generally less detrimental for quality of life. The endoscopic removal of pre-malignant lesions also reduces the incidence of CRC by stopping the progression to cancer. Colorectal cancers and adenomatous polyps bleed has providing fecal blood haemoglobin as the biomarker of choice for current screening programmes. Stool samples could be periodically taken and analyzed for the presence of occult blood, as an early sign of colorectal lesions (adenoma or CRC).

Target condition
Adenomas, as non-malignant precursor lesions of ColoRectal Cancer (CRC).
Target condition description

CRC is the third most common in incidence and the fourth most common cause of cancer death worldwide. CRC is particularly suitable for screening. The disease is believed to develop in a vast majority of cases from non-malignant precursor lesions called adenomas. Adenomas can occur anywhere in the colorectum after a series of mutations that cause neoplasia of the epithelium. At some time , the adenoma may invade the submucosa and become malignant. Initially, this malignant cancer is not diagnosed and does not give symptoms  (preclinical phase). It can progress from localised (stage I) to metastasised (stage IV) cancer, until it causes symptoms and is diagnosed. Only 5–6% of the population actually develop CRC. The average duration of the development of an adenoma to CRC is estimated to be  at least 10 years. This long latent phase provides a window of opportunity for early detection of the disease.

Target population

Target population sex: Any. Target population age: adults and elderly. Target population group: Healthy and/or asymptomatic people.

Target population description

Adults, average risk of CRC, aged 50 years or over.

The best age range for offering gFOBT or FIT screening has not been investigated in trials. Circumstantial evidence suggests that mortality reduction from gFOBT is similar in different age ranges between 45 and 80 years .The age range for a national screening programme should at least include people aged 60 to 64 years in which CRC incidence and mortality are high and life-expectancy is still considerable. Only the FOBT for men and women aged 50–74 years has been recommended todate by the EU (Council Recommendation and the European guidelines for quality assurance in CRC screening and diagnosis).

Members of families with hereditary syndromes, previous diagnosis of CRC or pre-malignant lesions should follow specific surveillance protocols and are not included in the target population

ComparisonCRC screening with Guaiac –based fecal occult blood test (gFOBT)
Description

CRC screening with Guaiac–based fecal occult blood test (gFOBT)

The guaiac-based FOBT is still a commonly used method for detecting blood in faeces. To detect hemoglobin the test uses guaiac gum and its efficacy as a colorectal cancer screening test has been analyzed in several randomised controlled trials. The test detects the haem component of haemoglobin, which is identical across human and animal species and is chemically robust and only partially degraded during its passage through the gastrointestinal tract. gFOBTs cannot distinguish between human blood and blood residues from the diet.

Many guaiac-based tests are currently on the market (like Coloscreen, Helena Laboratories,Texas,USA; Hema-screen Immunostics Inc.; Hemoccult, Beckman Coulter Inc.; Hemoccult SENSA, Beckman Coulter Inc.; MonoHaem, Chemicon Europe Ltd; Hema-Check, Siemens PLC; HemaWipe, Medtek Diagnostics LLC)

The use of the test is considered under conditions of population based colorectal cancer screening, in the context of organised cancer screening programmes as recommended by the EU. Population-based programmes have been rolled out nationwide in several European countries. Many member states  haveestablished nationwide non-population-based programmes. Some states are planning or piloting a nationwide population-based programme. These have  adopted only FOBT, some only FIT, some a mix between FOBT and endoscopy, or only colonoscopy.

Outcomes

CUR and TEC

  • Health problems (target condition)
  • Epidemiology
  • Burden of disease
  • Target population
  • Current management of the condition
  • Features of the technology
  • Life-Cycle
  • Regulatory status
  • Utilization
  • Investments and tools required to use the technology
  • Training and information needed to use the technology

SAF

  • Colonoscopy probability of perforation
  • Colonoscopy with polypectomy probability of perforation
  • Colonoscopy probability of death following perforation
  • Probability of bleeding following colonoscopy
  • Psychological harms from false-negatives and false-positives (and generally from participating in screening program)

EFF

  • Test (FIT and gFOBT) sensitivity for adenomas
  • Test (FIT and gFOBT) sensitivity for cancer
  • Test (FIT and gFOBT) specificity for adenomas
  • Test (FIT and gFOBT) specificity for cancer 
  • Adenoma incidence (detection rates)
  • Rectal cancer incidence (detection rates)
  • Colon cancer incidence (detection rates)
  • CRC incidence (detection rates)
  • Stage distribution of detected cancers
  • Rectal cancer specific mortality
  • CRC specific mortality
  • Overall mortality
  • Life years saved

ECO:

  • Model/template for  national pilots  to assess the costs and benefits of the two alternative  technologies FIT and gFOBT  and also no-programmed-screening
  • Systematic literature search of   available models and/or economic  evaluation for screening colorectal cancer with FIT and gFOBT and no screening programme
  • Resource Utilization: Publicly funded health care payer costs (screening tests, further examinations e.g. labor, colonoscopy  and treatments and administration and organisation costs of screening programme) for FIT and gFOBT (in cooperation with ORG)
  • Cost per Case detected (average, marginal, incremental) =  intermediate outcome – optional, not decided yet (relevant for deciding how often a test should be carried out and what are the incremental costs for a “new” detected case
  • Indirect Costs: not for the Core modell (should be decided later on)
  • Test accuracy: from SAF
  • Cost effectiveness analysis: HRQoL measures (both generic and context specific) (EFF and SAF for help, own Lit.research), ICER

 ORG:

  • Responsiveness of target population to invitation
  • Invitation-reminder system
  • Competence of human resources – health professionals
  • Investments needed (material,equipment)
  • Costs of using both tests (FIT, gFOBT)
  • Timeliness of results and future phases
  • Use of tools for process monitoring (completed check lists)
  • Model for Budget Impact Analysis from perspective of the payer

SOC

  • Compliance with the tests (FIT, gFOBT)
  • Anxiety and any psychological effects of using  one test or another
  • Information, counseling, communication (quality of) for the use of tests
  • Satisfaction  
  • Quality of life
  • Equity of access

LEG

  • Information as baseline for an informed consent
  • Harms or inequities that can be taken to court

Assessment elements

TopicIssue RelevantResearch questions or rationale for irrelevance
E0001Resource utilizationWhat types of resources are used when delivering the assessed technology and its comparators (resource use identification)?yesWhat types of resources are used when delivering FIT and its comparators gFOBT and no screening(resource use identification)?
E0002Resource utilizationWhat amounts of resources are used when delivering the assessed technology and its comparators (resource use measurement)?yesWhat amounts of resources are used when delivering FIT and its comparators gFOBT and no screening (resource use measurement)?
E0003Unit costsWhat are the unit costs of the resources used when delivering the assessed technology and its comparators?yesWhat are the unit costs of the resources used when delivering FIT and its comparators gFOBT and no screening?
E0005OutcomesWhat are the incremental effects of the technology relative to its comparator(s)?yesWhat are the incremental effects of FIT relative to its comparator(s)gFOBT and no screening?
E0006Cost-effectivenessWhat is the incremental cost-effectiveness ratio?yesWhat is the incremental cost-effectiveness ratio (FIT versus gFOBT; FIT versus no screening; gFOBT versus no screening)?
E0007Cost-effectivenessWhat is the appropriate time horizon?yesWhat is the appropriate time horizon?
E0008Cost-effectivenessWhat is the method of analysis?yesWhat is the method of analysis?
E0004Indirect CostsWhat is the impact of the technology on indirect costs?nothe indirect costs are not considered because the study is carried out from the perspective of the health care payer/system; furthermore, if QALYs are used as outcome measure, there is discussion in the scientific community, that there might be double counting; additionally the decision makers, responsible for the implementation of a screening technology, are mainly interested in the costs for the health care system

Methodology description

The following elements will be assessed within the domain “Cost and Economic Evaluation” (ECO):

Result card

Topic

Research question

ECO1

Resource use

What types of resources are used when delivering FIT and its comparator gFOBT?

ECO2

Resource use

What amounts of resources are used when delivering FIT and its comparator gFOBT?

ECO3

Unit costs

What are the unit costs of the resources used when delivering FIT and its comparator gFOBT?

ECO4

Outcomes

What are the incremental effects of FIT relative to its comparator gFOBT?

ECO5

Cost-effectiveness

What is the incremental cost-effectiveness ratio (FIT versus gFOBT)?

ECO6

Cost-effectiveness

What is the appropriate time horizon?

ECO7

Cost-effectiveness

What is the method of analysis?

 

Indirect costs are not covered to any great extent in this domain because a health-care payer perspective has been adopted in most of the studies found. The main reason for exclusion of indirect costs may be that most decision makers consider only health care resource costs in the base case for the evaluation of screening programmes and studies that include indirect costs are rare. With respect to this domain, decision makers who are responsible for implementing a screening program should be aware that the studies focus is almost entirely on the direct costs for the health care system, with little attention to potential wider economic impacts. Further details related to impact on budgets can be found from results card ORG7, from the Organisational aspects -domain.

Information sources

A systematic literature search was conducted using the CRD, Cochrane and PubMed databases to identify studies that are based on cost-effectiveness models comparing FIT with gFOBT.

The results of the “Survey for retrieving information on the use of technology in European countries” did not yield enough information on the costs of screening using FIT and gFOBT and were therefore not included in the analysis.

Quality assessment tools or criteria

In the systematic literature review, the focus was on cost-effectiveness studies published in peer reviewed journals. Reviews, letters, comments, etc., were not considered for inclusion in the analysis of evidence, although HTA reports as well as other literature were used to gain a further perspective (see, e.g., {5, 6}). The search strategy was validated by achieving consensus among the investigators and reviewers of the ECO domain. The quality of the included studies was not formally assessed here, the reasons being that cost-effectiveness studies are generally aimed at providing an input into informed decision making and that there are both strengths and weaknesses in existing checklists {7}. These studies are often highly context specific (i.e., specific to the country, population, health care system, perspective, etc. in which the decision is being made). As a consequence, a study on cost-effectiveness considered as high-quality according to a reporting-quality checklist (such as {8, 9}) but may not be highly relevant for a decision maker in a different decision-making or policy context. On the other hand, a study classed by a checklist as ‘low-quality’ might include the best available evidence for a specific decision-making situation and, therefore, make a relevant contribution to informing the decision. 

Analysis and synthesis

A systematic literature search was conducted using different scientific databases (CRD, Cochrane and PubMed) in June 2013. The search was specifically aimed at identifying peer-reviewed literature containing cost-effectiveness models focusing on population-based colorectal cancer (CRC) screening using FIT vs. gFOBt. Studies comparing other screening strategies (e.g., flexible sigmoidoscopy or computed tomographic colonography) with only one of the two relevant strategies, either FIT or gFOBT, were excluded as well as studies that were not based on decision-analytic modelling. Articles that solely report clinical outcomes and studies looking only at costs were excluded since the primary aim of this domain is to gain insight into the results and the study design of published cost-effectiveness models.

After the systematic literature was completed, extensive citation tracking and non-systematic searching was conducted. This additional search was essential because, at this point in time, a general consensus is lacking about one or more standard terms used for the relatively new immunochemical screening technology. In the literature different terms or abbreviations for screening for CRC with an immunochemical faecal occult blood test are used and some of these were only identified on the basis of the systematic search results; the most common are FIT (faecal immunochemical test), iFOBT (immunochemical faecal occult blood test) or FOBT with HemeSelect, which is a specific immunochemical test. The latter term is often used in older studies (until 2000), whereas FIT is frequently used in the most recent studies. The detailed search strategies can be found in the Appendix.

Figure 1: Literature search

pdf10936.Eco-Figure 1

The decision to exclude studies was based on main two criteria: (1) the study does not compare a guaiac-based faecal occult blood test with an immunochemical based faecal occult blood test and (2) the study does not include a cost-effectiveness model. Other reasons for exclusion were a lack of relevance for the European context, focus on a different disease, or the published work being case studies, congress presentations, editorial letters, etc. (see the Appendix for detailed selection criteria). After screening the abstracts and evaluation of the full texts, 16 relevant articles {10-25} could be identified and included in the review. {26-37}

The results presented in this domain are a review of the included models but do not include a meta-analysis. A meta-analysis, amongst other things, would neglect the fact that the costs (result cards 1-3), incremental effects (result card 4) and as a consequence the cost-effectiveness (result card 5) ratios are influenced by the study design (type of model, perspective, time horizon, population etc.) and the input parameters (sensitivity, specificity, compliance rate, etc.) {38}. Building a generic cost-effectiveness model for Europe was regarded as not feasible within the time constraints of this pilot Core HTA, due to the need to allow for the modelling of different health-care systems and the epidemiological differences found in European countries. It was therefore considered more useful to provide a comprehensive overview of the existing published cost-effectiveness models as support and starting point for country-specific models developed in national reports. 

Result cards

Resource utilization

Result card for ECO1: "What types of resources are used when delivering FIT and its comparators gFOBT and no screening(resource use identification)?"

View full card
ECO1: What types of resources are used when delivering FIT and its comparators gFOBT and no screening(resource use identification)?
Method
Result

Importance: Important

Transferability: Completely

Result card for ECO2: "What amounts of resources are used when delivering FIT and its comparators gFOBT and no screening (resource use measurement)?"

View full card
ECO2: What amounts of resources are used when delivering FIT and its comparators gFOBT and no screening (resource use measurement)?
Method
Result
Comment

Importance: Critical

Transferability: Not

Unit costs

Result card for ECO3: "What are the unit costs of the resources used when delivering FIT and its comparators gFOBT and no screening?"

View full card
ECO3: What are the unit costs of the resources used when delivering FIT and its comparators gFOBT and no screening?
Method
Result

Importance: Optional

Transferability: Not

Outcomes

Result card for ECO4: "What are the incremental effects of FIT relative to its comparator(s)gFOBT and no screening?"

View full card
ECO4: What are the incremental effects of FIT relative to its comparator(s)gFOBT and no screening?
Method
Result
Comment

Importance: Critical

Transferability: Partially

Cost-effectiveness

Result card for ECO5: "What is the incremental cost-effectiveness ratio (FIT versus gFOBT; FIT versus no screening; gFOBT versus no screening)?"

View full card
ECO5: What is the incremental cost-effectiveness ratio (FIT versus gFOBT; FIT versus no screening; gFOBT versus no screening)?
Method
Result
Comment

Importance: Critical

Transferability: Partially

Result card for ECO6: "What is the appropriate time horizon?"

View full card
ECO6: What is the appropriate time horizon?
Method
Result

Importance: Unspecified

Transferability: Unspecified

Result card for ECO7: "What is the method of analysis?"

View full card
ECO7: What is the method of analysis?
Method
Result

Importance: Unspecified

Transferability: Unspecified

Discussion

The general limitation of model-based cost-effectiveness studies is that models represent a simplification of a complex reality. This limitation is clearly present in the Costs and economic evaluation domain where we included studies that use modelling to estimate the costs, effects and cost-effectiveness of colorectal cancer. For instance, many cost-effectiveness studies make the simplifying assumption that all colorectal cancers develop from adenomas, although this is unlikely to be the case {5}. A series of trade-offs have to be made, for instance, between complexity and transparency. Many of these models have been to some extent validated, or calibrated, against, e.g., estimates of efficacy in terms of CRC incidence or mortality from randomised trials and other literature. However, as there is no general means to validate or calibrate models in terms of their estimates of cost or cost effectiveness, readers should focus on their potential face validity given the inputs used, the extent to which models were transparently documented, and whether appropriate sensitivity analyses were performed. The benefit of model-based studies is that it allows the comparison of different screening tests where economic evaluations based on end-to-end trials might not be feasible. It enables researchers to put the two comparators in the same context (e.g. assuming the same quality of follow-up tests or cancer treatment), and therefore limit the analysis to the actual outcomes of the tests.

Issues relevant to numerous domains within this Core model include sensitivity and specificity, participation rate, age of the population to be screened, screening interval, different FIT thresholds. Below we highlight some of the issues from the literature which have some of the strongest effects on the estimates of cost and cost effectiveness.

It should be noted that the review presented in this domain is complicated by the fact that a majority of studies compare many screening modalities (e.g. faecal DNA test, flexible sigmoidoscopy, computed tomography colonoscopy, colon capsule endoscopy {13-15, 18, 20, 22, 23, 25}), rather than just FIT and FOBT. A difference is also discernible between those studies with a North American focus and those with a European focus. One of the main ways in which European studies may differ markedly from those in the US is in terms of the lower European level of health care and social care costs. For instance, the cost of testing kits, diagnostic procedures and both curative and palliative treatment may all be substantially higher in the US. The rate of increase in costs may also differ between Europe and the US, many studies have not incorporated the probable cost pressures caused by the new forms of chemotherapy {6}. Another culturally-specific issue is the pattern of adherence to screening protocols, for example, FOBT participation rates in Finland during the roll-out of a national screening programme were as high as 71% {40}, while in Italy adherence as part of a randomised controlled trial was recorded as 27% on average {41}. Most of the studies included in the review do not take into account that adherence, i.e., the level of participation in screening and post-screening protocols, may differ quantitatively {10-16, 18, 21-23, 25}, e.g., may depend on the screening modalities in question. However, even when studies do not assume perfect adherence relatively favourable estimates of cost-effectiveness are reported in base-case analyses {6}.

Given the use of a health-care payer perspective in many studies, when analysing costs, they naturally do not include costs which are borne by the patient or costs borne outside the health care system. Hence, in the studies found, many of the costs borne by individuals, which may vary according to the screening modality used, has not been taken into account in many models {5}. A variety of health-care-payer perspectives on costs was predominant in the studies found. It could also be informative if a societal perspective, which may include costs falling more widely both inside and outside the health-care system, would also have been investigated. It should be noted that the choice of a restricted perspective, such as the perspective of a health-care-payer, may affect both the ability to provide information on either static or dynamic economic efficiency, and the ability of estimates of cost-effectiveness to be usefully compared to analyses of other technologies which use a different or broader perspective.

There is still a dearth of information concerning health-related quality of life both for screening participants, as well as for individuals who undergo diagnosis and or treatment. One small-scale, now decades old, study of health-related quality of life amongst colorectal cancer patients is widely used in the estimates found in this literature review.

The choice between FIT and FOBT is complicated as both FIT and gFOBT are often used as generic names for a number of tests, for which the sensitivity and specificity, for example, vary. FOBT has had versions called Hemoccult ®, Hemoccult II and Hemoccult SENSA and FIT has been used with low-mid-high or other quantitative thresholds. The situation is complicated even further by the fact that there are different approaches of measuring the sensitivity and specificity of a screening test {33}.

Although a discount rate of 3% was widely used for both costs and benefits {10, 13, 16-18, 21, 24, 25}, in many of the studies reviewed here the rate of discount for costs and/or benefits was one of the parameters most influential on the resulting ICERs and, together with the chosen time horizon, careful consideration should be given to the applicability of the values used in the analysis {40}. The use of thorough sensitivity analyses concerning variations in discount rates is particularly advisable when a time horizon of extended duration is used.

It should also be remembered that estimates of the overall cost burden of initiating and maintaining a screening programme is usually considered to be beyond the scope of the ECO domain (see, e.g. {30}). The Core Model considers such costs within the Organisational domain.

Potential future research needs in the light of this systematic review:

  • Trial-based economic evaluations of FIT versus gFOBt, no screening, or opportunistic screening, with both mortality and morbidity endpoints (one such study, currently underway in Finland, is comparing gFOBT to no screening)
  • Thorough and transparent sensitivity analyses concerning variations in, e.g., discount rates and adherence 

References

1.         Ferlay J SH, Bray F, Forman D, Mathers C and Parkin DM. GLOBOCAN 2008 v2.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10.  2010  [cited 2013 September]; Available from: http://globocan.iarc.fr

2.         Colon; E. Prevention and screening [cited 2013 05.06.]; Available from: http://www.europacolon.com/preventionandscreening.php?Action=Preventionandscreening;

3.         Institute; NC. Tests to Detect Colorectal Cancer and Polyps 2013  [cited 2013 05.06.]; Available from: http://www.cancer.gov/cancertopics/factsheet/detection/colorectal-screening#r13

4.         (eds); SNPJvKL. European Guidelines for Quality Assurance in Colorectal Cancer Screening and Diagnosis - First Edition.  2013  [cited 2013 05.06.]; Available from: http://bookshop.europa.eu/is-bin/INTERSHOP.enfinity/WFS/EU-Bookshop-Site/en_GB/-/EUR/ViewPublication-Start?PublicationKey=ND3210390

5.         Health Information and Quality Authority of Ireland. Health technology assessment (HTA) of a population-based colorectal cancer screening programme in Ireland: Health Information and Quality Authority of Ireland (HIQA); 2009 2009-03-25.

6.         Lansdorp-Vogelaar I, Knudsen AB, Brenner H. Cost-effectiveness of colorectal cancer screening – An overview. Best Practice & Research Clinical Gastroenterology. 2010;24(4):439-49.

7.         Walker DG, Wilson RF, Sharma R, Bridges J, Niessen L, EB B. Best Practices for Conducting Economic Evaluations in Health Care: A Systematic Review of Quality Assessment Tools. : Rockville (MD); 2012.

8.         Damian G. Walker, Renee F. Wilson, Ritu Sharma, John Bridges, Louis Niessen, Eric B. Bass, et al. Best Practices for Conducting Economic Evaluations in Health Care: A Systematic Review of Quality Assessment Tools. Baltimore, MD: Johns Hopkins University Evidence-based Practice Center

2012.

9.         Don Husereau, Michael Drummond, Stavros Petrou M, Chris Carswell, David Moher, Dan Greenberg, et al. Consolidated health economic evaluation reporting standards (CHEERS)—Explanation and elaboration: A report of the ISPOR health economic evaluations publication guidelines good reporting practices task force. Value Health. 2013;15(2).

10.       Ballegooijen v, Habbema, Boer, Zauber, Brown. A comparison of the cost-effectiveness of fecal occult blood tests with different test characteristics in the context of annual screening in the Medicare population; 2003.

11.       Berchi, Guittet, Bouvier, Launvoy. Cost-effectiveness analysis of the optimal threshold of an automated immunochemical test for colorectal cancer screening: performances of immunochemical colorectal cancer screening. Int J Technol Assess Health Care. 2010;26(1).

12.       Berchi C, Bouvier V, Reaud JM, Launoy G. Cost-effectiveness analysis of two strategies for mass screening for colorectal cancer in France. Health Econ. 2004 Mar;13(3):227-38.

13.       Hassan, Benamouzig, Spada, Ponchon, Zullo, Saurin, et al. Cost effectiveness and projected national impact of colorectal cancer screening in France. Endoscopy. 2011;43(9).

14.       Heitman, Au, Hilsden, Manns. Fecal Immunochemical Testing in Colorectal Cancer Screening of Average Risk Individuals: Economic Evaluation. Ottawa; 2009.

15.       Heitman SJ, Hilsden RJ, Au F, Dowden S, Manns BJ. Colorectal cancer screening for average-risk North Americans: an economic evaluation. PLoS Med. 2010;7(11):e1000370.

16.       Heresbach D, Chauvin P, Grolier J, Josselin JM. Cost-effectiveness of colorectal cancer screening with computed tomography colonography or fecal blood tests. Eur J Gastroenterol Hepatol. 2010 Nov;22(11):1372-9.

17.       Lejeune C, Dancourt V, Arveux P, Bonithon-Kopp C, Faivre J. Cost-effectiveness of screening for colorectal cancer in France using a guaiac test versus an immunochemical test. Int J Technol Assess Health Care. 2010 Jan;26(1):40-7.

18.       Parekh M, Fendrick AM, Ladabaum U. As tests evolve and costs of cancer care rise: reappraising stool-based screening for colorectal neoplasia. Aliment Pharmacol Ther. 2008 Apr;27(8):697-712.

19.       Rossum v, Rijn v, Verbeek, Oijen v, Laheij, Fockens, et al. Colorectal cancer screening comparing no screening, immunochemical and guaiac fecal occult blood tests: a cost-effectiveness analysis. Int J Cancer. 2011;128(8).

20.       Sharp L, Tilson L, Whyte S, O'Ceilleachair A, Walsh C, Usher C, et al. Cost-effectiveness of population-based screening for colorectal cancer: a comparison of guaiac-based faecal occult blood testing, faecal immunochemical testing and flexible sigmoidoscopy. Br J Cancer. 2012 Feb 28;106(5):805-16.

21.       Sobhani I, Alzahouri K, Ghout I, Charles DJ, Durand-Zaleski I. Cost-effectiveness of mass screening for colorectal cancer: choice of fecal occult blood test and screening strategy. Dis Colon Rectum. 2011 Jul;54(7):876-86.

22.       Telford JJ, Levy AR, Sambrook JC, Zou D, Enns RA. The cost-effectiveness of screening for colorectal cancer. CMAJ. 2010 Sep 7;182(12):1307-13.

23.       Whyte S, Chilcott J, Halloran S. Reappraisal of the options for colorectal cancer screening in England. Colorectal Dis. 2012 Sep;14(9):e547-61.

24.       Wilschut JA, Habbema JD, van Leerdam ME, Hol L, Lansdorp-Vogelaar I, Kuipers EJ, et al. Fecal occult blood testing when colonoscopy capacity is limited. J Natl Cancer Inst. 2011 Dec 7;103(23):1741-51.

25.       Zauber AG. Cost-effectiveness of colonoscopy. Gastrointest Endosc Clin N Am. 2010 Oct;20(4):751-70.

26.       Haug U, Knudsen AB, Kuntz KM. How should individuals with a false-positive fecal occult blood test for colorectal cancer be managed? A decision analysis. Int J Cancer. 2012 Nov 1;131(9):2094-102.

27.       Labianca R, Beretta GD, Mosconi S, Milesi L, Pessi MA. Colorectal cancer: screening. Ann Oncol. 2005;16 Suppl 2:ii127-32.

28.       Lejeune C, Arveux P, Dancourt V, Fagnani F, Bonithon-Kopp C, Faivre J. A simulation model for evaluating the medical and economic outcomes of screening strategies for colorectal cancer. Eur J Cancer Prev. 2003 Feb;12(1):77-84.

29.       Robinson MHE, Marks CG, Farrands PA, Whynes DK, Bostock K, Hardcastle JD. Is an immunological faecal occult blood test better than Haemoccult? A cost-benefit study. european Journal of Surgical Oncology. 1995;21.

30.       Sharp, Tilson, Whyte, O`Ceilleachair, Walsh, Usher, et al. Using resource modelling to inform decision making and service planning: the case of colorectal cancer screening in Ireland. BMC Health Service Research. 2013;March 19(13).

31.       Castiglione, Zappa, Grazzini, Sani, Mazzotta, Mantelli, et al. Cost analysis in a population based screening programme for colorectal cancer: comparison of immunochemical and guaiac faecal occult blood testing. Journal of Medical Screening. 1997;4(3).

32.       Frazier AL, Colditz GA, Fuchs CS, Kuntz KM. Cost-effectiveness of Screening for Colorectal Cancer in the General Population. Journal of the American Medical Association. 2000;284(15).

33.       Gyrd-Hansen D. Fecal Occult-Blood Tests - A cost-effectiveness Analysis. International Journal of Technology Assessment in Health Care. 1998;14(2).

34.       Ladabaum U, Song K. Projected national impact of colorectal cancer screening on clinical and economic outcomes and health services demand. Gastroenterology. 2005 Oct;129(4):1151-62.

35.       Pignone MP, Flitcroft KL, Howard K, Trevena LJ, Salkeld GP. Costs and cost-effectiveness of full implementation of a biennial faecal occult blood test screening program for bowel ancer in Australia. MJA. 2011;194(4).

36.       Sonnenberg A, Delco F, Inadomi JM. Cost-effectiveness of Colonoscopy in Screening for Colorectal Cancer. Annals of Internal Medicine. 2000;133(8).

37.       Whynes DK. Cost-effectiveness of faecal occult blood screening for colorectal cancer: results of the Nottingham trial. Critical Reviews in Oncology/Hematology. 1998;32.

38.       Anderson R. Systematic reviews of economic evaluations: utility or futility? . Health Economics. 2010;19(3).

39.       Connor R, Chu K, Smart C. Stage-shift cancer screening model. Journal of Clinical Epidemiology. 1989;42(11).

40.       Malila N, Oivanen T, Malminiemi O, Hakama M. Test, episode, and programme sensitivities of screening for colorectal cancer as a public health policy in Finland: experimental design. Bmj. 2008;337:a2261.

41.       Lisi D, Hassan C, Crespi M, Group AS. Participation in colorectal cancer screening with FOBT and colonoscopy: an Italian, multicentre, randomized population study. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2010 May;42(5):371-6.

 

Appendices

  • Systematic literature search

    pdf10936.ECO-Appendix 1

  • Selection Criteria

    pdf10936.ECO-Appendix 2

  • Study designs and results

    pdf10936.ECO-Appendix 3

     

     

Ethical analysis

Authors: Gottfried Endel

Summary

A comparison of tests with identical test characteristic, similar accuracy and identical types of consequences pose no specific ethical problems. If a regional health care system has already decided to implement a population based screening for colorectal cancer the main ethical issues are already decided. A choice of the screening test for occult blood in faeces is very similar to the decision which product to choose, if there are different vendors.

The variability of ICERs in ECO5 shows that the tests are really very similar. They both dominate no screening but the indirect comparison of the two tests varies considerably. Even so most models attribute dominance to FIT some are favorable for gFOBT. To address these uncertainties an appraisal of the HTA information with application of regional values and experiences has to be done. There the usual framework for decisions in the respective health care system can be applied. This should also cover the question of opportunity cost if the decision imposes a financial impact on the sytem.

Introduction

Questions addressing (population) screening activities need a special approach in ethical analysis. There are the following points with a framework different from usual treatment interventions:

  • The health care system recommends an intervention. So it is a system responsibility to provide the information needed for an informed consent to participate. The best available evidence and open information about uncertainty has to be made available.
  • The intervention addresses asymptomatic = “healthy” people. So issues of safety, quality and harm reduction have first priority. This influences the approach to a risk / benefit balance.
  • As it is a recommendation of the health care system the quality of the service provision has to be monitored and the results have to be evaluated. Results have to be published and data has to be made available.
  • The use of public resources needs special legitimating and proof of evidence.

There is also no information in medical literature about the basics of a health care system. The challenge in a core HTA is to be specific on an European level but according to the organization of health care in the member states only to outline the questions and principles addressed so they can be applied on the local level.

In the case of the comparison of Fecal Immunochemical Test (FIT) for detection of occult blood in the stool associated with colorectal lesions (adenomas and colorectal cancer-CRC), under conditions of population based colorectal cancer screening, comparing with CRC screening with Guaiac –based fecal occult blood test (gFOBT) only the questions of the effectiveness and safety of the test in combination with the economic consequences are of interest. These questions are covered in the corresponding domains.

Methodology

Frame

The collection scope is used in this domain.

TechnologyFecal Immunochemical Test (FIT) for colorectal cancer screening
Description

FITs use an antibody (immunoglobulin) specific to human globin, the protein component of haemoglobin, to detect fecal occult blood. Immunochemical tests have improved test characteristics compared to conventional guaiac-based tests for fecal occult blood. FIT should not be subject to interference from dietary blood and it is more specific to bleeding from the distal gastrointestinal tract. They could be analytically and clinically more sensitive and specific, Their measurement can be automated and the user can adjust the concentration at which a positive result is reported. A wide range of qualitative and quantitative tests is presently available, with varying levels of sensitivity and specificity (like Hem-SP/MagStream H, Fujirebio Inc. Japan ; OC-Sensor, Eiken Chemical Co., Tokyo, Japan;    FOB Gold, Medinostics Products Supplier; Sentinel Diagnostics SpA, Milan, Italy).

Intended use of the technologyScreening

CRC screening with faecal inmunochemical test (FIT) for detection of occult blood in the stool associated with colorectal lesions (adenomas and CRC).

The use of the test is considered under conditions of population based colorectal cancer screening, in the context of organised cancer screening programmes as recommended by the EU. Early detection and treatment of colorectal lesions before they become symptomatic has the potential to improve control of the disease, reducing morbidity and mortality associated to CRC. Early treatment of invasive lesions can be generally less detrimental for quality of life. The endoscopic removal of pre-malignant lesions also reduces the incidence of CRC by stopping the progression to cancer. Colorectal cancers and adenomatous polyps bleed has providing fecal blood haemoglobin as the biomarker of choice for current screening programmes. Stool samples could be periodically taken and analyzed for the presence of occult blood, as an early sign of colorectal lesions (adenoma or CRC).

Target condition
Adenomas, as non-malignant precursor lesions of ColoRectal Cancer (CRC).
Target condition description

CRC is the third most common in incidence and the fourth most common cause of cancer death worldwide. CRC is particularly suitable for screening. The disease is believed to develop in a vast majority of cases from non-malignant precursor lesions called adenomas. Adenomas can occur anywhere in the colorectum after a series of mutations that cause neoplasia of the epithelium. At some time , the adenoma may invade the submucosa and become malignant. Initially, this malignant cancer is not diagnosed and does not give symptoms  (preclinical phase). It can progress from localised (stage I) to metastasised (stage IV) cancer, until it causes symptoms and is diagnosed. Only 5–6% of the population actually develop CRC. The average duration of the development of an adenoma to CRC is estimated to be  at least 10 years. This long latent phase provides a window of opportunity for early detection of the disease.

Target population

Target population sex: Any. Target population age: adults and elderly. Target population group: Healthy and/or asymptomatic people.

Target population description

Adults, average risk of CRC, aged 50 years or over.

The best age range for offering gFOBT or FIT screening has not been investigated in trials. Circumstantial evidence suggests that mortality reduction from gFOBT is similar in different age ranges between 45 and 80 years .The age range for a national screening programme should at least include people aged 60 to 64 years in which CRC incidence and mortality are high and life-expectancy is still considerable. Only the FOBT for men and women aged 50–74 years has been recommended todate by the EU (Council Recommendation and the European guidelines for quality assurance in CRC screening and diagnosis).

Members of families with hereditary syndromes, previous diagnosis of CRC or pre-malignant lesions should follow specific surveillance protocols and are not included in the target population

ComparisonCRC screening with Guaiac –based fecal occult blood test (gFOBT)
Description

CRC screening with Guaiac–based fecal occult blood test (gFOBT)

The guaiac-based FOBT is still a commonly used method for detecting blood in faeces. To detect hemoglobin the test uses guaiac gum and its efficacy as a colorectal cancer screening test has been analyzed in several randomised controlled trials. The test detects the haem component of haemoglobin, which is identical across human and animal species and is chemically robust and only partially degraded during its passage through the gastrointestinal tract. gFOBTs cannot distinguish between human blood and blood residues from the diet.

Many guaiac-based tests are currently on the market (like Coloscreen, Helena Laboratories,Texas,USA; Hema-screen Immunostics Inc.; Hemoccult, Beckman Coulter Inc.; Hemoccult SENSA, Beckman Coulter Inc.; MonoHaem, Chemicon Europe Ltd; Hema-Check, Siemens PLC; HemaWipe, Medtek Diagnostics LLC)

The use of the test is considered under conditions of population based colorectal cancer screening, in the context of organised cancer screening programmes as recommended by the EU. Population-based programmes have been rolled out nationwide in several European countries. Many member states  haveestablished nationwide non-population-based programmes. Some states are planning or piloting a nationwide population-based programme. These have  adopted only FOBT, some only FIT, some a mix between FOBT and endoscopy, or only colonoscopy.

Outcomes

CUR and TEC

  • Health problems (target condition)
  • Epidemiology
  • Burden of disease
  • Target population
  • Current management of the condition
  • Features of the technology
  • Life-Cycle
  • Regulatory status
  • Utilization
  • Investments and tools required to use the technology
  • Training and information needed to use the technology

SAF

  • Colonoscopy probability of perforation
  • Colonoscopy with polypectomy probability of perforation
  • Colonoscopy probability of death following perforation
  • Probability of bleeding following colonoscopy
  • Psychological harms from false-negatives and false-positives (and generally from participating in screening program)

EFF

  • Test (FIT and gFOBT) sensitivity for adenomas
  • Test (FIT and gFOBT) sensitivity for cancer
  • Test (FIT and gFOBT) specificity for adenomas
  • Test (FIT and gFOBT) specificity for cancer 
  • Adenoma incidence (detection rates)
  • Rectal cancer incidence (detection rates)
  • Colon cancer incidence (detection rates)
  • CRC incidence (detection rates)
  • Stage distribution of detected cancers
  • Rectal cancer specific mortality
  • CRC specific mortality
  • Overall mortality
  • Life years saved

ECO:

  • Model/template for  national pilots  to assess the costs and benefits of the two alternative  technologies FIT and gFOBT  and also no-programmed-screening
  • Systematic literature search of   available models and/or economic  evaluation for screening colorectal cancer with FIT and gFOBT and no screening programme
  • Resource Utilization: Publicly funded health care payer costs (screening tests, further examinations e.g. labor, colonoscopy  and treatments and administration and organisation costs of screening programme) for FIT and gFOBT (in cooperation with ORG)
  • Cost per Case detected (average, marginal, incremental) =  intermediate outcome – optional, not decided yet (relevant for deciding how often a test should be carried out and what are the incremental costs for a “new” detected case
  • Indirect Costs: not for the Core modell (should be decided later on)
  • Test accuracy: from SAF
  • Cost effectiveness analysis: HRQoL measures (both generic and context specific) (EFF and SAF for help, own Lit.research), ICER

 ORG:

  • Responsiveness of target population to invitation
  • Invitation-reminder system
  • Competence of human resources – health professionals
  • Investments needed (material,equipment)
  • Costs of using both tests (FIT, gFOBT)
  • Timeliness of results and future phases
  • Use of tools for process monitoring (completed check lists)
  • Model for Budget Impact Analysis from perspective of the payer

SOC

  • Compliance with the tests (FIT, gFOBT)
  • Anxiety and any psychological effects of using  one test or another
  • Information, counseling, communication (quality of) for the use of tests
  • Satisfaction  
  • Quality of life
  • Equity of access

LEG

  • Information as baseline for an informed consent
  • Harms or inequities that can be taken to court

Assessment elements

TopicIssue RelevantResearch questions or rationale for irrelevance
F0001Principal questions about the ethical aspects of technologyIs the technology a new, innovative mode of care, an add-on to or modification of a standard mode of care or a replacement of a standard?yesIs FIT a new, innovative mode of care, an add-on to or modification of a standard mode of care or a replacement of a standard?
F0002Principal questions about the ethical aspects of technologyCan the technology challenge religious, cultural or moral convictions or beliefs of some groups or change current social arrangements?noThis would only be relevant between organized and opportunistic screening. But it's no question between two tests.
F0003Principal questions about the ethical aspects of technologyWhat can be the hidden or unintended consequences of the technology and its applications for different stakeholders.noThis would only be relevant between organized and opportunistic screening. But it's no question between two tests.
F0006AutonomyCan the technology entail special challenges/risk that the patient/person needs to be informed of?yesCan FIT entail special challenges/risk that the patient/person needs to be informed of?
F0004AutonomyDoes the implementation or use of the technology challenge patient autonomy?noThis would only be relevant between organized and opportunistic screening. But it's no question between two tests.
F0005AutonomyIs the technology used for patients/people that are especially vulnerable?noThis would only be relevant between organized and opportunistic screening. But it's no question between two tests.
F0007AutonomyDoes the implementation challenge or change professional values, ethics or traditional roles?noThis would only be relevant between organized and opportunistic screening. But it's no question between two tests.
F0010Beneficence/nonmaleficenceWhat are the benefits and harms for patients, and what is the balance between the benefits and harms when implementing and when not implementing the technology? Who will balance the risks and benefits in practice and how?yesWhat are the benefits and harms for patients, and what is the balance between the benefits and harms when implementing and when not implementing FIT? Who will balance the risks and benefits in practice and how?
F0011Beneficence/nonmaleficenceCan the technology harm any other stakeholders? What are the potential benefits and harms for other stakeholders, what is the balance between them? Who will balance the risks and benefits in practice and how?noThis would only be relevant between organized and opportunistic screening. But it's no question between two tests.
F0012Justice and EquityWhat are the consequences of implementing / not implementing the technology on justice in the health care system? Are principles of fairness, justness and solidarity respected?yesWhat are the consequences of implementing / not implementing FIT on justice in the health care system? Are principles of fairness, justness and solidarity respected?
F0013Justice and EquityHow are technologies presenting with relevantly similar (ethical) problems treated in health care system?yesHow are technologies presenting with relevantly similar (ethical) problems treated in health care system?
F0017Questions about effectiveness and accuracyWhat are the proper end-points for assessment and how should they be investigated?yesWhat are the proper end-points for assessment and how should they be investigated?
F0018Questions about effectiveness and accuracyAre the accuracy measures decided and balanced on a transparent and acceptable way?yesAre the accuracy measures decided and balanced on a transparent and acceptable way?
F0008Human DignityDoes the implementation or use of the technology affect human dignity?noThis would only be relevant between organized and opportunistic screening. But it's no question between two tests.
F0009Human integrityDoes the implementation or use of the technology affect human integrity?noThis would only be relevant between organized and opportunistic screening. But it's no question between two tests which are equivalent in this respect.
F0014RightsDoes the implementation or use of the technology affect the realisation of basic human rights?noThis would only be relevant between organized and opportunistic screening. But it's no question between two tests.
F0016LegislationIs legislation and regulation to use the technology fair and adequate?noThis would only be relevant between organized and opportunistic screening. But it's no question between two tests.

Methodology description

The project scope is applied in this domain. The ethical dimension of questions already covered in other domains adds only minor extensions to the findings there.

Information sources

The discussion of ethical issues is based on the results of the other domains and addresses in a discursive manner of coherence analysis (CA) according to the methodological recommendations for these domain aspects which were already covered but not scrutinized with regards to ethical aspects included. This methodological approach is chosen to minimize overlap and to take into account the potential of regional differences in values and opinions regarding potential marginal differences for ongoing programs.

Nevertheless a literature search was performed to find ethical discussions comparing these two tests or comparing two very similar tests in general. The search in pubmed and google sholar produced no literature addressing these issues. Articles on ethical issues for the questions of

  • screening versus no screening
  • screening with tests of very different risks for patients (FOBT versus colonoscopy)
  • organized population based screening versus no screening or opportunistic screening

were identified. Also a framework for ethical questions in public health referred to some common questions of screening but did not expand the comprehensive methodological guidance available for the core model.

Quality assessment tools or criteria

As the goal on the level of the core HTA is to define the framework for the ethical analysis only criteria for the application of this framework will be defined. The quality assessment than can be done by using these criteria in the local scope. There the specific answer to the questions of the element cards have to be found by gathering the local information necessary.

As mentioned as method CA was chosen. The main idea of CA is to reflect upon the consistency of ethical argumentations or broader theories on different levels, without prescribing which facts, arguments or principles are prima facie relevant. It is a procedural, pragmatic approach, i.e. describes a procedure of approaching moral issues without claims of providing direct answers on “right or wrong”. This supports regional adaptation by focusing discussions on the value given special criteria in the specific context of the own health care system.

The criteria to consider coming from the effectiveness domain are:

  • Test (FIT and gFOBT) sensitivity for adenomas
  • Test (FIT and gFOBT) sensitivity for cancer
  • Test (FIT and gFOBT) specificity for adenomas
  • Test (FIT and gFOBT) specificity for cancer
  • Adenoma incidence (detection rates)
  • Rectal cancer incidence (detection rates)
  • Colon cancer incidence (detection rates)
  • CRC incidence (detection rates)
  • Stage distribution of detected cancers
  • Rectal cancer specific mortality
  • CRC specific mortality
  • Overall mortality
  • Life years saved

The criteria to consider coming from the safety domain are:

  • Harms from colonoscopy
  • Psychological harms

The criteria to consider coming from the economic domain are:

  • Cost effectiveness
  • ICER
  • LYG
  • QUALY

Analysis and synthesis

The main sources for the ethical analysis are the results of the other domains. As shown in the EUNetHTA member survey of the domain on current use of the technologies CRC screening programs are widely ongoing in Europe. So the discussion of isolated aspects will be provided and no attempt is done to produce a synthesis fitting all different regional conditions and frameworks. The isolated aspects may – if appropriate – support the local adaptation of the assessment.

Result cards

Principal questions about the ethical aspects of technology

Result card for ETH1: "Is FIT a new, innovative mode of care, an add-on to or modification of a standard mode of care or a replacement of a standard?"

View full card
ETH1: Is FIT a new, innovative mode of care, an add-on to or modification of a standard mode of care or a replacement of a standard?
Method
Result

Importance: Important

Transferability: Completely

Autonomy

Result card for ETH2: "Can FIT entail special challenges/risk that the patient/person needs to be informed of?"

View full card
ETH2: Can FIT entail special challenges/risk that the patient/person needs to be informed of?
Method
Result

Importance: Important

Transferability: Completely

Beneficence/nonmaleficence

Result card for ETH3: "What are the benefits and harms for patients, and what is the balance between the benefits and harms when implementing and when not implementing FIT? Who will balance the risks and benefits in practice and how?"

View full card
ETH3: What are the benefits and harms for patients, and what is the balance between the benefits and harms when implementing and when not implementing FIT? Who will balance the risks and benefits in practice and how?
Method
Result

Importance: Important

Transferability: Unspecified

Justice and Equity

Result card for ETH4: "What are the consequences of implementing / not implementing FIT on justice in the health care system? Are principles of fairness, justness and solidarity respected?"

View full card
ETH4: What are the consequences of implementing / not implementing FIT on justice in the health care system? Are principles of fairness, justness and solidarity respected?
Method
Result

Importance: Important

Transferability: Partially

Result card for ETH5: "How are technologies presenting with relevantly similar (ethical) problems treated in health care system?"

View full card
ETH5: How are technologies presenting with relevantly similar (ethical) problems treated in health care system?
Method
Result

Importance: Optional

Transferability: Not

Questions about effectiveness and accuracy

Result card for ETH6: "What are the proper end-points for assessment and how should they be investigated?"

View full card
ETH6: What are the proper end-points for assessment and how should they be investigated?
Method
Result

Importance: Optional

Transferability: Completely

Result card for ETH7: "Are the accuracy measures decided and balanced on a transparent and acceptable way?"

View full card
ETH7: Are the accuracy measures decided and balanced on a transparent and acceptable way?
Method
Result

Importance: Important

Transferability: Partially

Discussion

The comparison of two tests to detect occult blood in faeces poses no serious ethical problems. The main issues regarding screening arise in the field of autonomy of the individual – which should be taken care of with objective information -, the measurement of benefits and harms – as done in the domains of EFF and SAF – and justice – this is addressed mostly in the ECO domain.

As the characteristics of the tests, their consequences and the informational content in a population based screening are structural identical ethical considerations for the marginal differences are not necessary. The information documented in the other domains suffices to support an appraisal process on the regional level. This appraisal to apply the framework of the regional values used in a specific health care system may address uncertainties which remain although with this collection of HTA information at hand.

Organisational aspects

Authors: Principal investigators: Valentina Prevolnik Rupel, Nika Berlic Investigators: Dominika Novak Mlakar, Taja Čokl, Plamen Dimitrov, Marta López de Argumedo

Summary

The manner in which CRC screening is carried out varies significantly from country to country within the EU, both in terms of organization and the screening test chosen. A screening program of one sort or another has been implemented in 19 of 27 EU countries. Results have shown that some countries have organized screening and some countries have the opportunistic one. European guidelines compared those two screening types and, according to the reviewed evidence, showed that organised screening programmes achieve better coverage of the target population including hard to- reach or disadvantaged groups that opportunistic. It is also more cost-effective and provides greater protection against the harms of screening, including over screening, poor quality and complications of screening, and poor follow-up of participants with positive test results.

The most frequently applied method in Europe is testing stool for occult bleeding (fecal occult blood test, FOBT). In 2007, gFOBT (which in 2003 was the only test recommended by the Council of the European Union) was used as the only screening method in twelve countries (Bulgaria, Czech Republic, Finland, France, Hungary, Latvia, Portugal, Romania, Slovenia, Spain, Sweden, and United Kingdom). In six countries, two types of tests were used: FIT and FS in Italy, and gFOBT and colonoscopy in Austria, Cyprus, Germany, Greece, and Slovak Republic. Since then FIT is becoming increasingly popular. For example: Slovenia, since 2009, when national CRC screening programme FIT has been adopted, uses FIT technology. According to the survey, implemented among 11 European countries (i. e. Austria, Russia, Luxembourg, Lithuania, Italy, Scotland, Spain, Romania, France, Croatia and Slovenia), it is seen that only 6 countries (Russia, Lithuania, Italy, Scotland, Spain and Slovenia) out of 11 uses FIT technology. Other countries, which participated to the survey, use gFOBT technology, with exception of Austria (excluding the Burgenland that uses FIT technology), who uses colonoscopy as a primary screening method. In addition to that Luxembourg indicated that FIT is relatively new technology and isn't widely accepted in their country. All countries stated that FIT and gFOBT screening are free of charge for target population and founded by the country.

FIT screening, like other screening methods, have to follow specific procedure: from identifying target population, sending invitation, re-invitation where it is necessary, delivering kits (The test kit may be delivered by mail, at GPs’ offices or outpatient clinics, by pharmacists, or in other community facilities, and in some cases with the support of volunteers.), collecting samples (via e-mail, or through volunteers for example – like in some countries), laboratory examination and follow up.

National screening programme gives criteria based on risk information about who should receive screening invitations. The target population for a CRC screening programme includes all people eligible to attend screening on the basis of age and geographical area of residence. According to Table 1 and Table 2 (see ORG1), some differences about the target population exist between European countries. In general, people who are between 50 and 75 are invited to the screening. Table 1 offers also information on operational characteristics.

Several studies found FIT as a better option in comparison to gFOBT, due to the fact that FIT:

·         Has no need for dietary restriction that results in better screening participation;

·         Needs a smaller number of stool samples than gFOBT;

·         Shows a greater relative sensitivity than gFOBT;

·         Shows a greater sensitivity for the detection of advanced adenomas than gFOBT;

·         Has a higher recall rate than most gFOBTs;

·         Has a PPV similar to those obtained with most gFOBTs;

·         Provides an opportunity of using a numeric threshold to find the most appropriate balance between sensitivity and specificity (i.e. between detection rate and positivity to the test); and

·         Allows the opportunity to balance recall and detection rates providing each country with the tools to implement a colorectal cancer screening programme that will meet local healthcare expectations within available resources.

·         But still, it has a major problem with sample instability, and collected samples should preferably be kept cool and returned immediately for analysis;

As regarding the participants’ and important others’ involvement into screening process and their own care and treatment, it has been showed (according to one study) that the attitudes towards CRC screening are strongly correlated with participation. Some other studies revealed participants' low awareness of the faecal occult blood test before they received the invitation for screening. Two of the major factors that influence the participation in screening programme are therefore an increasing knowledge and provision of more accessible screening programmes.

The success of a colorectal cancer screening programme depends on specially trained individuals committed to implementation, provision and evaluation of a high quality, efficient service. The multidisciplinary team that is responsible for a colorectal screening programme within FIT screening method includes:

·         Administrative, clerical staff,

·         Epidemiologists,

·         Laboratory staff,

·         Primary care physicians,

·         Nurses and also

·         Public health specialists.

Where screening tests are positive and further examination, treatment or care are necessary, the team also includes:

·         Endoscopists,

·         Radiologists,

·         Pathologists and

·         Surgeons.

But quality assurance cannot be achieved without a proper communication – in all levels. Cancer and screening communication messages must be therefore designed and delivered to match the communication skills, needs, and pre-dispositions of specific audiences. A key component of CRC screening programmes is, therefore, the information and education provided about CRC and CRC screening tests and procedures.

Communication among professionals is essential in order to ensure that all the information coming from the prognostic tests is available quickly and is correctly interpreted. To achieve and maintain an effective communication between the various professionals of a colorectal multidisciplinary team it is essential that they participate to different training courses, which should be focused on good inter-professional communication. Joint courses given for the multidisciplinary team may facilitate this goal. Good communication should be carried out between the members of the screening team with agreed terminology, regular meetings and clinical discussions.

Although colorectal cancer screening is recommended by major policy-making organizations, rates of screening remain low. Studies examine different communication tool options to increase knowledge on colorectal cancer screening and also to its participation. Studies also examine how communication factors influence CRC screening.

Literature provided little information on the impact of de-centralisation/ centralisation on implementation of FIT. Nevertheless some general conclusions about advantages and disadvantages of centralized and/or decentralized systems could be drawn; studies reveals that decentralized clinics and activities provide better access to health campaigns, who offers more information and knowledge to the participants and therefore influences on individuals participation to the screening. In the other hand in the centralized services the development of teams of different disciplines are more easily to arrange, they achieve economies of scale and can make better efficient use of a scarce resource and they also provide better outcomes for patients under the care due to the larger team of specialist professionals, for example – for cancer survival.

For implementation of FIT several investments are needed: a) material: e.g. equipment for screening, premises, office material for posting invitations and re-invitations, IT equipment and other office devices such as printers, and b) human resources: administrative and health personnel, investment in education of personnel and their training. Every country needs to assess their costs independently using cost-effectiveness analyses or other economic evaluation method. Investments that are needed for implementation of FIT are therefore country specific.

Data of budget impact of the implementation of FIT for the different payers were, by the literature review, not found. The existing studies examine only cost-effectiveness of performing FIT. The study of cost-effectiveness is important due to its impact on the payers’ decision about budget allocation and about the amount of financial resources that they will invest in the national screening programme and into a new technology. Although it has been expected that the information on the budget impact is going to be obtained through a survey, it can be concluded that information obtained from the survey were not sufficient for the budget impact analysis. In addition to that only two countries have indicated the costs that are related to the screening (i.e. Lithuania and Slovenia). We believe that further research and in-depth studies would be necessary to indicate the budget impact of the implementation of FIT for the payers.

According to the insight that was gained through the literature review, it can be concluded that the most critical points in management are:

·         To ensure that all eligible target population is invited and well informed about the colorectal cancer, colorectal cancer screening and the screening process;

·         To ensure that screening process is conducted strictly according to the rules of procedure (the quality of process depend also on the communication, coordination etc.);

·         To ensure an adequate and timely follow-up or treatment for those, who needs it;

·         To ensure the availability of data (data management system);

FIT method has been, among patients, well accepted. The studies have shown that FIT slightly outperforms gFOBT with a lower level of reported discomfort and overall burden. There are little information about the acceptance of FIT by health personnel and the organization. Nevertheless it has been demonstrated that the higher acceptability of FIT among patients is an important argument for choosing FIT in preference to gFOBT as the screening method for a nation-wide screening programme, apart from additional arguments regarding test performance characteristics. The additional information from the survey is going to enhance and backed the data on acceptance of FIT by health personnel and the organization.

Wide spectrums of stakeholders are engaged in planning and implementation of FIT. Usually stakeholders, involved in that process, vigorously defend their many interests, including patients, health professionals, politicians and industry. Little information exists about the interest groups/ stakeholders, who are or have to be taken into account in the planning / implementation of FIT. Only two reports were found – UK and Australian – to be relevant to this question. In addition, some information was gained through the survey.

For reaching quality assurance of FIT testing a consistency in analytical performance must be assured by the adoption and application of rigorous quality assurance procedures. Manufacturer’s Instructions for Use must be followed. Laboratories should perform daily checks of analytical accuracy and precision across the measurement range with particular emphasis at the selected cut-off limit. Rigorous procedures need to be agreed and adopted on how internal quality control data is interpreted and how the laboratory responds to unsatisfactory results. Performance data, both internal quality control and external quality assessment data, should be shared and reviewed by a Quality Assurance team working across the programme. Sufficient instrumentation should be available to avoid delays in analysis due to instrument failure or maintenance procedures.

Whilst an immunochemical test is recommended, programmes that adopt a traditional guaiac test need to apply additional laboratory quality procedures.

The prime importance of quality assurance should also be included in basic training of the staff that is engaged in screening process.

Quality assurance is strongly connected to the monitoring. All aspects of the cancer screening programme should be monitored and evaluated. Quality standards need to be set for every step along the screening pathway and an appropriate monitoring framework is required to determine if the standards are being met. Standards will apply at a number of levels: to procedures; individuals; teams; institutions and overall systems.

In the case of FIT cancer screening programme, where screening is based on a laboratory test, it is self-evident that an adequate monitoring system should be present in laboratories.

All laboratories providing screening services should be associated with a laboratory accredited to ISO 15189:2007 Medical laboratories - Particular requirements for quality and competence. The laboratories should perform Internal Quality Control (IQC) procedures and participate in an appropriate External Quality Assessment Scheme (EQAS).

Of fundamental importance is also the complete and accurate recording of all relevant data on each individual and every screening test performed - including the test results, the decisions made as a consequence, diagnostic and treatment procedures and the subsequent outcome, including cause of death.

In order to be able to evaluate the effectiveness of screening, the data must be linked at the individual level to several external data sources including population register, cancer or pathology registries, and registries of cause of death in the target population. Therefore, legal authorisation should be put in place when the screening programme is introduced in order to be able to carry out programme evaluation by linking the above-mentioned data for follow-up.

Introduction

The organisational domain considers what types of resources (material, human skills, knowledge, money, etc.) must be mobilised and organised when implementing a technology, and what changes or consequences the use can cause in an organisation and a health care system as a whole. The issues include e.g. quality and sustainability assurance, centralization, communication, managerial structure and acceptance. There are three levels to consider regarding organizational aspects: intra-organizational, inter-organizational and health care system level. The levels of approach can also be divided into micro level (patient interaction), mezzo level (health care organization and community) and macro level (health policy).

The growing focus of organizational issues in health technology assessment (HTA) indicates a recognition that many decisions on resource allocation in provision of technologies are of crucial importance. Organizational aspects in HTA influence the behaviour of managers and health professionals. Also policy makers on the national level need knowledge on organizational aspects, when making decisions on the use of technologies. Organizational aspects in HTA may clarify challenges and barriers in implementing health technologies {1}.

In this core HTA the objective is to assess the organisational effects of FIT (Fecal immunochemical Test) for colorectal cancer screening, also called as iFOBT (immunochemical FOBT) screening, compared with the guaiac-based fecal occult blood test (gFOBT) for colorectal cancer screening, both within organized screening program. 

Methodology

Frame

The collection scope is used in this domain.

TechnologyFecal Immunochemical Test (FIT) for colorectal cancer screening
Description

FITs use an antibody (immunoglobulin) specific to human globin, the protein component of haemoglobin, to detect fecal occult blood. Immunochemical tests have improved test characteristics compared to conventional guaiac-based tests for fecal occult blood. FIT should not be subject to interference from dietary blood and it is more specific to bleeding from the distal gastrointestinal tract. They could be analytically and clinically more sensitive and specific, Their measurement can be automated and the user can adjust the concentration at which a positive result is reported. A wide range of qualitative and quantitative tests is presently available, with varying levels of sensitivity and specificity (like Hem-SP/MagStream H, Fujirebio Inc. Japan ; OC-Sensor, Eiken Chemical Co., Tokyo, Japan;    FOB Gold, Medinostics Products Supplier; Sentinel Diagnostics SpA, Milan, Italy).

Intended use of the technologyScreening

CRC screening with faecal inmunochemical test (FIT) for detection of occult blood in the stool associated with colorectal lesions (adenomas and CRC).

The use of the test is considered under conditions of population based colorectal cancer screening, in the context of organised cancer screening programmes as recommended by the EU. Early detection and treatment of colorectal lesions before they become symptomatic has the potential to improve control of the disease, reducing morbidity and mortality associated to CRC. Early treatment of invasive lesions can be generally less detrimental for quality of life. The endoscopic removal of pre-malignant lesions also reduces the incidence of CRC by stopping the progression to cancer. Colorectal cancers and adenomatous polyps bleed has providing fecal blood haemoglobin as the biomarker of choice for current screening programmes. Stool samples could be periodically taken and analyzed for the presence of occult blood, as an early sign of colorectal lesions (adenoma or CRC).

Target condition
Adenomas, as non-malignant precursor lesions of ColoRectal Cancer (CRC).
Target condition description

CRC is the third most common in incidence and the fourth most common cause of cancer death worldwide. CRC is particularly suitable for screening. The disease is believed to develop in a vast majority of cases from non-malignant precursor lesions called adenomas. Adenomas can occur anywhere in the colorectum after a series of mutations that cause neoplasia of the epithelium. At some time , the adenoma may invade the submucosa and become malignant. Initially, this malignant cancer is not diagnosed and does not give symptoms  (preclinical phase). It can progress from localised (stage I) to metastasised (stage IV) cancer, until it causes symptoms and is diagnosed. Only 5–6% of the population actually develop CRC. The average duration of the development of an adenoma to CRC is estimated to be  at least 10 years. This long latent phase provides a window of opportunity for early detection of the disease.

Target population

Target population sex: Any. Target population age: adults and elderly. Target population group: Healthy and/or asymptomatic people.

Target population description

Adults, average risk of CRC, aged 50 years or over.

The best age range for offering gFOBT or FIT screening has not been investigated in trials. Circumstantial evidence suggests that mortality reduction from gFOBT is similar in different age ranges between 45 and 80 years .The age range for a national screening programme should at least include people aged 60 to 64 years in which CRC incidence and mortality are high and life-expectancy is still considerable. Only the FOBT for men and women aged 50–74 years has been recommended todate by the EU (Council Recommendation and the European guidelines for quality assurance in CRC screening and diagnosis).

Members of families with hereditary syndromes, previous diagnosis of CRC or pre-malignant lesions should follow specific surveillance protocols and are not included in the target population

ComparisonCRC screening with Guaiac –based fecal occult blood test (gFOBT)
Description

CRC screening with Guaiac–based fecal occult blood test (gFOBT)

The guaiac-based FOBT is still a commonly used method for detecting blood in faeces. To detect hemoglobin the test uses guaiac gum and its efficacy as a colorectal cancer screening test has been analyzed in several randomised controlled trials. The test detects the haem component of haemoglobin, which is identical across human and animal species and is chemically robust and only partially degraded during its passage through the gastrointestinal tract. gFOBTs cannot distinguish between human blood and blood residues from the diet.

Many guaiac-based tests are currently on the market (like Coloscreen, Helena Laboratories,Texas,USA; Hema-screen Immunostics Inc.; Hemoccult, Beckman Coulter Inc.; Hemoccult SENSA, Beckman Coulter Inc.; MonoHaem, Chemicon Europe Ltd; Hema-Check, Siemens PLC; HemaWipe, Medtek Diagnostics LLC)

The use of the test is considered under conditions of population based colorectal cancer screening, in the context of organised cancer screening programmes as recommended by the EU. Population-based programmes have been rolled out nationwide in several European countries. Many member states  haveestablished nationwide non-population-based programmes. Some states are planning or piloting a nationwide population-based programme. These have  adopted only FOBT, some only FIT, some a mix between FOBT and endoscopy, or only colonoscopy.

Outcomes

CUR and TEC

  • Health problems (target condition)
  • Epidemiology
  • Burden of disease
  • Target population
  • Current management of the condition
  • Features of the technology
  • Life-Cycle
  • Regulatory status
  • Utilization
  • Investments and tools required to use the technology
  • Training and information needed to use the technology

SAF

  • Colonoscopy probability of perforation
  • Colonoscopy with polypectomy probability of perforation
  • Colonoscopy probability of death following perforation
  • Probability of bleeding following colonoscopy
  • Psychological harms from false-negatives and false-positives (and generally from participating in screening program)

EFF

  • Test (FIT and gFOBT) sensitivity for adenomas
  • Test (FIT and gFOBT) sensitivity for cancer
  • Test (FIT and gFOBT) specificity for adenomas
  • Test (FIT and gFOBT) specificity for cancer 
  • Adenoma incidence (detection rates)
  • Rectal cancer incidence (detection rates)
  • Colon cancer incidence (detection rates)
  • CRC incidence (detection rates)
  • Stage distribution of detected cancers
  • Rectal cancer specific mortality
  • CRC specific mortality
  • Overall mortality
  • Life years saved

ECO:

  • Model/template for  national pilots  to assess the costs and benefits of the two alternative  technologies FIT and gFOBT  and also no-programmed-screening
  • Systematic literature search of   available models and/or economic  evaluation for screening colorectal cancer with FIT and gFOBT and no screening programme
  • Resource Utilization: Publicly funded health care payer costs (screening tests, further examinations e.g. labor, colonoscopy  and treatments and administration and organisation costs of screening programme) for FIT and gFOBT (in cooperation with ORG)
  • Cost per Case detected (average, marginal, incremental) =  intermediate outcome – optional, not decided yet (relevant for deciding how often a test should be carried out and what are the incremental costs for a “new” detected case
  • Indirect Costs: not for the Core modell (should be decided later on)
  • Test accuracy: from SAF
  • Cost effectiveness analysis: HRQoL measures (both generic and context specific) (EFF and SAF for help, own Lit.research), ICER

 ORG:

  • Responsiveness of target population to invitation
  • Invitation-reminder system
  • Competence of human resources – health professionals
  • Investments needed (material,equipment)
  • Costs of using both tests (FIT, gFOBT)
  • Timeliness of results and future phases
  • Use of tools for process monitoring (completed check lists)
  • Model for Budget Impact Analysis from perspective of the payer

SOC

  • Compliance with the tests (FIT, gFOBT)
  • Anxiety and any psychological effects of using  one test or another
  • Information, counseling, communication (quality of) for the use of tests
  • Satisfaction  
  • Quality of life
  • Equity of access

LEG

  • Information as baseline for an informed consent
  • Harms or inequities that can be taken to court

Assessment elements

TopicIssue RelevantResearch questions or rationale for irrelevance
G0001ProcessWhat kind of work flow, participant flow and other processes are needed?yesWhat kind of work flow, participant flow and other processes are needed?
G0002ProcessWhat kind of involvement has to be mobilized for participants and important others?yesWhat kind of involvement has to be mobilized for participants and important others?
G0003ProcessWhat kind of staff, training and other human resources are required?yesWhat kind of staff, training and other human resources are required?
G0004ProcessWhat kind of co-operation and communication of activities have to be mobilised?yesWhat kind of co-operation and communication of activities have to be mobilised?
G0012ProcessWhat kind of quality assurance is needed and how should it be organised?yesWhat kind of quality assurance is needed and how should it be organised?
G0005StructureHow does de-centralisation or centralization requirements influence the implementation of the technology?yesHow does de-centralisation or centralization requirements influence the implementation of FIT?
G0006StructureWhat kinds of investments are needed (material or premises) and who are responsible for those?yesWhat kinds of investments are needed (material or premises) and who are responsible for those?
G0007StructureWhat is the likely budget impact of the implementation of the technology for the payers (e.g. government)?yesWhat is the likely budget impact of the implementation of FIT for the payers (e.g. government)?
G0008ManagementWhat management problems and opportunities are attached to the technology?yesWhat management problems and opportunities are attached to FIT?
G0013ManagementWhat kind of monitoring requirements and opportunities are there for the technology?yesWhat kind of monitoring requirements and opportunities are there for FIT?
G0009ManagementWho decides which people are eligible for the technology and on what basis?noIn comapring gFOBT and FIT in organized screening the eligibility of the population is the same as it is based on incidence and prevalence.
G0010CultureHow is the technology accepted?yesHow is FIT accepted?
G0011CultureHow are the other interest groups taken into account in the planning / implementation of the technology?yesHow are the other interest groups taken into account in the planning / implementation of FIT?

Methodology description

Domain frame

The project scope is applied in this domain.

Technology

FIT for colorectal cancer screening vs. gFOBT colorectal cancer screening in organized screening program

Description

Procedure of gFOBT: the standard fecal occult blood (FOBT) test can detect small amounts of blood in the stool by submitting a portion of three consecutive bowel movements for testing. The test cannot identify polyps and some diet restrictions need to be considered, as the test is not specific for human blood alone. gFOBT is used for more than 30 years in routine, is widely available and inexpensive. If the test is positive, a colonoscopy will be needed to find the reason for the bleeding {2, 3}.

Procedure of FIT: FIT (Fecal Immunochemical Test) for colorectal cancer screening, also called as iFOBT (immunochemical FOBT) screening, is more accurate than FOBT as it only identifies human blood. It needs only one stool sample, thus is more simple to complete. If the test is positive, a colonoscopy will be needed to find the reason for the bleeding {2, 3}.

Colorectal cancer (CRC) screening with faecal inmunochemical test (FIT) for detection of occult blood in the stool associated with colorectal lesions (adenomas and CRC) is considered under conditions of population based colorectal cancer screening, in the context of organised cancer screening programmes as recommended by the EU. Early detection and treatment of colorectal lesions before they become symptomatic has the potential to improve control of the disease, reducing morbidity and mortality associated to CRC. Early treatment of invasive lesions can be generally less detrimental for quality of life. The endoscopic removal of pre-malignant lesions also reduces the incidence of CRC by stopping the progression to cancer. Stool samples could be periodically taken and analyzed for the presence of occult blood, as an early sign of colorectal lesions (adenoma or CRC).

To ensure effectiveness, the screening interval in a national screening programme should not exceed two years for gFOBT and three years for FIT {4}.

Purpose of use: detect cancer, polyps, nonpolypoid lesions, which are flat or slightly depressed areas of abnormal cell growth and can also develop into colorectal cancer.

Intended use of the technology

Screening

CRC screening with faecal immunochemical test (FIT)

Target condition

Adenomas, as non-malignant precursor lesions of Colorectal Cancer (CRC).

Target condition description

CRC is the third most common in incidence and the fourth most common cause of cancer death worldwide. CRC is particularly suitable for screening. The disease is believed to develop in a vast majority of cases from non-malignant precursor lesions called adenomas. Adenomas can occur anywhere in the colorectum after a series of mutations that cause neoplasia of the epithelium. Adenoma may invade the submucosa and become malignant. Initially, this malignant cancer is not diagnosed and does not cause symptoms (preclinical phase). It can progress from localised (stage I) to metastasised (stage IV) cancer, until it causes symptoms and is diagnosed. Only 5–6% of the general population actually develop CRC. The average duration of the development of an adenoma to CRC is estimated to be at least 10 years. This long latent phase provides a window of opportunity for early detection of the disease.

Target population

Target population sex: any. Target population age: 50-74 years. Target population group: Asymptomatic people.

Target population description

Adults (both men and women), average risk of CRC, aged 50 years or over.

The best age range for offering gFOBT or FIT screening has not been investigated in trials. Circumstantial evidence suggests that mortality reduction from gFOBT is similar in different age ranges between 45 and 80 years. The age range for a national screening programme should at least include people aged 60 to 64 years in which CRC incidence and mortality are high and life-expectancy is still considerable. EU Council Recommendations suggests only the faecal occult blood test (gFOBT or FIT) for men and women aged 50–74 for CRC screening {4}.

Members of families with hereditary syndromes, previous diagnosis of CRC or pre-malignant lesions should follow specific surveillance protocols and are not included in the target population.

 

Comparison

CRC screening with Guaiac – based fecal occult blood test (gFOBT)

Description

CRC screening with Guaiac–based fecal occult blood test (gFOBT)

The guaiac-based FOBT is still a commonly used method for detecting blood in faeces. To detect hemoglobin the test uses guaiac gum and its efficacy as a colorectal cancer screening test has been analysed in several randomised controlled trials. The test detects the haem component of haemoglobin, which is identical across human and animal species and is chemically robust and only partially degraded during its passage through the gastrointestinal tract. gFOBTs cannot distinguish between human blood and blood residues from the diet.

Many guaiac-based tests are currently on the market (like Coloscreen, Helena Laboratories,Texas,USA; Hema-screen Immunostics Inc.; Hemoccult, Beckman Coulter Inc.; Hemoccult SENSA, Beckman Coulter Inc.; MonoHaem, Chemicon Europe Ltd; Hema-Check, Siemens PLC; HemaWipe, Medtek Diagnostics LLC).

The use of the test is considered under conditions of population based colorectal cancer screening in the context of organised cancer screening programmes as recommended by the EU. Population-based programmes have been rolled out nationwide in several European countries. Many member states have established nationwide non-population-based programmes. Some states are planning or piloting a nationwide population-based programme. These have adopted only gFOBT, some only FIT, some a mix between FOBT and endoscopy, or only colonoscopy.

 

ASSESSMENT ELEMENTS

Question number

ID

Topic

Issue

Relevant

Research questions or rationale for irrelevance

ORG1

G0001

Process

What kind of work flow, participant flow and other processes are needed?

yes

What kind of work flow, participant flow and other processes are needed?

ORG2

G0002

Process

What kind of involvement has to be mobilized for participants and important others?

yes

What kind of involvement has to be mobilized for participants and important others?

ORG3

G0003

Process

What kind of staff, training and other human resources are required?

yes

What kind of staff, training and other human resources are required?

ORG4

G0004

Process

What kind of co-operation and communication of activities have to be mobilised?

yes

What kind of co-operation and communication of activities have to be mobilised?

ORG5

G0005

Structure

How does de-centralisation or centralization requirements influence the implementation of the technology?

yes

How does de-centralisation or centralization requirements influence the implementation of FIT?

ORG6

G0006

Structure

What kinds of investments are needed (material or premises) and who are responsible for those?

yes

What kinds of investments are needed (material or premises) and who are responsible for those?

ORG7

G0007

Structure

What is the likely budget impact of the implementation of the technology for the payers (e.g. government)?[1]

yes

What is the likely budget impact of the implementation of FIT for the payers (e.g. government)?

ORG8

G0008

Management

What management problems and opportunities are attached to the technology?

yes

What management problems and opportunities are attached to the FIT?

ORG9

G0010

Culture

How is the technology accepted?

yes

How is FIT accepted?

ORG10

G0011

Culture

How are the other interest groups taken into account in the planning / implementation of the technology?

yes

How are the other interest groups taken into account in the planning / implementation of FIT?

ORG11

G0012

Process

What kind of quality assurance is needed and how should it be organised?

yes

What kind of quality assurance is needed and how should it be organised?

ORG12

G0013

Management

What kind of monitoring requirements and opportunities are there for the technology?

yes

What kind of monitoring requirements and opportunities are there for FIT?

 

Information sources

Organisational aspects are rarely covered in clinical studies or HTA reports so the current analysis required several activities. Systematic review of the literature was not enough to answer the research question of this domain. So grey literature and national guidelines were added. Since some organizational aspects are very much linked to country contexts, it is useful to integrate results with the experience of local experts in the area. For this purpose the results of the survey was used.

Quality assessment tools or criteria

In the systematic literature review, only studies with organizational aspect, published in peer reviewed journals were selected. Reviews, letters, comments, etc., were not considered for inclusion in the analysis of evidence. These studies are often highly context specific (i.e., specific to the country, population, health-care system).

Hereinafter exclusion and inclusion criteria are presented in more detail:

Exclusion criteria:

a)     Formal exclusion criteria

·         Studies not published in English

·         Duplicates

·         Studies irrelevant for the European context

b)     Thematic exclusion criteria

·         Different research question

·         Different disease or clinical focus (e.g. other diseases than colorectal cancer)

·         Other intervention (i.e. no comparison between FIT and gFOBT)

c)      Study design

·         Congress presentation, posters, „Comments“, „Letters“ etc. (i.e.. „Abstracts“, not based on any actual primary study)

·         Case studies

·         Studies not focusing on human medicine (e.g. animal studies) or in-vitro Studies

 

Inclusion criteria:

·         Basic requirements fulfilled (none of the above exclusion criteria is applicable)

·         HTA / systematic Review

·         Study presents an organizational aspect

 

To summarize,  inclusion criteria for ORG domain were:

1.      The studies compared a guaiac-based faecal occult blood test (gFOBT) with an immunochemical based faecal occult blood test (FIT),

2.      The studies considered the organizational aspect,

3.      The studies were relevant for the European context.

 

Analysis and synthesis

Literature search was conducted in May 2013. Descriptive analysis was performed on different information sources. The assessment elements questions were answered by Principal investigator and complemented and reviewed by investigators.   Literature search was specifically aimed at identifying peer-reviewed literature containing organizational aspect on population based colorectal cancer screening using FIT and gFOBT. After systematic literature was completed, non-systematic searching for other literature (grey literature) and survey were conducted. The details of all three steps in this process of information searching are described below:

1.      A literature search and review of the results

A systematic literature search was conducted in May 2013. Published literature was obtained by searching: ACADEMIC SEARCH COMPLETE (EBSCO), WILEY ONLINE LIBRARY, SCIENCE DIRECT, SPRINGER LINK, ERIC (EBSCO) and JSTOR. Additional searches were done through the Internet engine Google, where guidelines, reports and some free articles/ studies on Oxford journals, PubMed etc. were found.

The search was performed using key words of each identity card (i.e. each research question). More detailed description of literature (key words) are described in Appendix 1 (i.e. search strategies).

pdf10936.ORG Methodology-Figure 1

2.      Grey literature and national guidelines searches

Grey literature was searched for the ORG1, ORG5, ORG6, ORG10 and ORG12 assessment elements. Details of the searches are covered in those elements and the identified literature is included in the domain references. Grey literature was not searched for any other assessment element.

32 relevant articles/studies were found, one international guidelines and two international reports. In addition, two publications were found, one national report and one national guidelines (through an Internet engine Google). Six other grey resources ware found through an Internet engine Google. We also used EUnetHTA WP4 CORE HTA basic document, published on EUnetHTA intranet, as a background document.

3.      A survey

The survey for retrieving information on the use of technology in European countries has been implemented. 11 European countries have participated to the survey: Austria, Russia, Luxembourg, Lithuania, Italy, Scotland, Spain, Romania, France, Croatia and Slovenia.

Institutions that participated to the survey are listed in table below (Table 1):

Table 1: Institutions that participated to the survey

CountryInstitution

Austria

Ludwig Boltzmann Institute for Health Technology Assessment

Russia

National Center for Health Technology Assessment - NCHTA

Luxembourg

Cellule d'expertise médicale

Lithuania

State Health Care Accreditation Agency under the Ministry of Health

Italy

•             Laziosanità – ASP (Agenzia di Sanità Pubblica della Regione Lazio è l'organo strumentale della Regione in materia sanitaria)

•             Veneto Region

Scotland

Healthcare Improvement Scotland

Spain

Andalusian Agency for Health Technology Assessment  - AETSA

Romania

National School of Public Health, Management and Professional Development - NSPHMPD

France

HAS

Croatia

Agency for Quality and Accreditation in Health Care and Social Welfare

Slovenia

National Institute of Public Health

A survey gives answers on question ORG7 and the supplement to the answers on following questions: ORG5, ORG6 and ORG10. The survey gives additional information also to the questions ORG1 and ORG9.

  [1] This question should be included in the ECO domain.

Result cards

Process

Result card for ORG1: "What kind of work flow, participant flow and other processes are needed?"

View full card
ORG1: What kind of work flow, participant flow and other processes are needed?
Method
Frame
Result
Comment

Importance: Critical

Transferability: Completely

Result card for ORG2: "What kind of involvement has to be mobilized for participants and important others?"

View full card
ORG2: What kind of involvement has to be mobilized for participants and important others?
Method
Frame
Result
Comment

Importance: Critical

Transferability: Completely

Result card for ORG3: "What kind of staff, training and other human resources are required?"

View full card
ORG3: What kind of staff, training and other human resources are required?
Method
Frame
Result
Comment

Importance: Critical

Transferability: Completely

Result card for ORG4: "What kind of co-operation and communication of activities have to be mobilised?"

View full card
ORG4: What kind of co-operation and communication of activities have to be mobilised?
Method
Frame
Result
Comment

Importance: Critical

Transferability: Completely

Result card for ORG11: "What kind of quality assurance is needed and how should it be organised?"

View full card
ORG11: What kind of quality assurance is needed and how should it be organised?
Method
Frame
Result
Comment

Importance: Critical

Transferability: Partially

Structure

Result card for ORG5: "How does de-centralisation or centralization requirements influence the implementation of FIT?"

View full card
ORG5: How does de-centralisation or centralization requirements influence the implementation of FIT?
Method
Frame
Result
Comment

Importance: Critical

Transferability: Partially

Result card for ORG6: "What kinds of investments are needed (material or premises) and who are responsible for those?"

View full card
ORG6: What kinds of investments are needed (material or premises) and who are responsible for those?
Method
Frame
Result
Comment

Importance: Critical

Transferability: Partially

Result card for ORG7: "What is the likely budget impact of the implementation of FIT for the payers (e.g. government)?"

View full card
ORG7: What is the likely budget impact of the implementation of FIT for the payers (e.g. government)?
Method
Frame
Result
Comment

Importance: Critical

Transferability: Partially

Management

Result card for ORG8: "What management problems and opportunities are attached to FIT?"

View full card
ORG8: What management problems and opportunities are attached to FIT?
Method
Frame
Result
Comment

Importance: Critical

Transferability: Partially

Result card for ORG12: "What kind of monitoring requirements and opportunities are there for FIT?"

View full card
ORG12: What kind of monitoring requirements and opportunities are there for FIT?
Method
Frame
Result
Comment

Importance: Critical

Transferability: Partially

Culture

Result card for ORG9: "How is FIT accepted?"

View full card
ORG9: How is FIT accepted?
Method
Frame
Result
Comment

Importance: Critical

Transferability: Partially

Result card for ORG10: "How are the other interest groups taken into account in the planning / implementation of FIT?"

View full card
ORG10: How are the other interest groups taken into account in the planning / implementation of FIT?
Method
Frame
Result
Comment

Importance: Important

Transferability: Not

Discussion

Based on the European Guidelines for Quality Assurance in Colorectal Cancer Screening and Diagnosis - First Edition and on the Report on the implementation of the Council Recommendation on cancer screening – First Report, sufficient overview of organizational aspect of FIT has been given. We have substantiated and strengthen the answers with several studies and also other resources that have been found on the web site. However those two documents on all the other resources were not enough to gain a complete insight into countries’ specific organizational situation and also for gaining an insight into the budgetary issues.

The current overview can be therefore used as a starting point for further – country specific – examination. For this purpose an international survey was executed.

References

  1. Eunetha (WP4 Core HTA). HTA Core Model online; 2012.
  2. National cancer institute [Internet]. Tests to Detect Colorectal Cancer and Polyps [cited 2013-05-06]; Available on: http://www.cancer.gov/cancertopics/factsheet/detection/colorectal-screening#r13;
  3. Europa Colon [Internet]. Prevention and screening [cited 2013-05-06]; Available from: http://www.europacolon.com/preventionandscreening.php?Action=Preventionandscreening;
  4. Segnan N, Patnick J, von Karsa L (eds). European Guidelines for Quality Assurance in Colorectal Cancer Screening and Diagnosis - First Edition [cited 2013-05-06]; Available from: http://bookshop.europa.eu/is-bin/INTERSHOP.enfinity/WFS/EU-Bookshop-Site/en_GB/-/EUR/ViewPublication-Start?PublicationKey=ND3210390; 2010.
  5. Von Karsa et. al. Cancer Screening in the European Union. Report on the implementation of the Council Recommendation on cancer screening – First Report [cited 2013-05-06]; Available from: http://ec.europa.eu/health/archive/ph_determinants/genetics/documents/cancer_screening.pdf; 2008.
  6. Zavoral, Miroslav et. al. Colorectal cancer screening in Europe. World J Gastroenterol 2009; 15(47): 5907-5915.
  7. Institute of Biostatics and Analysis [Internet]. National colorectal cancer screening programme in Slovenia – Svit Programme. II. European colorectal cancer days – Brno 2013 - prevention and screening: Stakeholder Meeting [cited 2013-06-21] Available from: http://www.crcprevention.eu/res/file/presentations/06-novak-mlakar.pdf
  8. Benson, S. Victoria et. al. Toward standardizing and reporting colorectal cancer screening indicators on an international level: the International Colorectal Cancer Screening Network. International Journal of Cancer 2011; 130: 2961–2973.
  9. Kanavos, Panos et. al. [Internet] Colorectal cancer in Europe and Australia: challenges and opportunities for the future [cited 2013-05-19]. Available from: http://www.tumori.net/it3/brochures/documenti/ColorectalCancerReport.pdf, 2008.
  10. Ascunce N. et al. Cancer Screening in Spain. Annals of Oncology 2010. 21 (3):iii43-iii51.
  11. Swan, Heidi et. al. International Colorectal Cancer Screening Programs: Population Contact Strategies, Testing Methods and Screening Rates [cited 2013-05-06]; Available from: http://www.practicalgastro.com/pdf/August12/Swan.pdf; 2012.
  12. Van Dam L. et. al. What influences the decision to participate in colorectal cancer screening with faecal occult blood testing and sigmoidoscopy? European Journal of Cancer 2013 [cited 2013-05-14]; Available from: http://dx.doi.org/10.1016/j.ejca.2013.03.007;  
  13. Azodo, P. Ijeoma. Participation in bowel cancer screening: an exploration of the processes involved. The Lancet 2012; 380: S24.
  14. Kreps, G.L.  The impact of communication on cancer risk, incidence, morbidity, mortality, and quality of life.  Health Communication 2003; 15: 2, 163-171.
  15. Yoo, Woohyun et. al. Influence of communication on colorectal cancer screening: Revisiting the Health Belief Model. Journal of Communication in Healthcare 2013; vol. 6 no. 1: 35-43.
  16. Rowe, Sara et. al. Health Care Providers’ Perspectives of an Intervention Designed to Improve Colorectal Cancer Screening Rates in Family Medicine Residency Clinics – A Qualitative Study. J Canc Educ 2012; 27: 695–702.
  17. Kim, Jane. et. al. Development and initial testing of a computer-based patient decision aid to promote colorectal cancer screening for primary care practice. BMC Medical Informatics and Decision Making 2005, 5:36.
  18. Miller Jr, P. David et. al. Effectiveness of a Web-Based Colorectal Cancer Screening Patient Decision Aid A Randomized Controlled Trial in a Mixed-Literacy Population. Am J Prev Med 2011; 40(6): 608–615.
  19. Cueva, Melany et. al. Readers’ Theatre: A Communication Tool for Colorectal Cancer Screening. J Canc Educ 2012; 27: 281–286.
  20. Redmond, Jennifer et. al. Effectively Communicating Colorectal Cancer Screening Information to Primary Care Providers: Application for State, Tribe or Territory comprehensive cancer control coalitions. American Journal of Health Education 2012; 43, 4; ProQuest pg. 194.
  21. Royal College of General practitioners. Trend towards centralisation of hospital services, and its effect on access to care for rural and remote communities in the UK. Rutal and remote health 2005; 5:390.
  22. Saltman, B. Richard, et. al. [Internet] Decentralization in health care [cited 2013-05-16]; Available from:  http://www.euro.who.int/__data/assets/pdf_file/0004/98275/E89891.pdf; 2007.
  23. UCLA Newsroom [Internet]. Centralized health care more cost-effective, offers better access to preventive services [cited 2013-05-16]. Available from: http://newsroom.ucla.edu/portal/ucla/centralized-health-care-systems-171264.aspx; 2010.
  24. Poncet, Florence et. al. Determinants of participation in organized colorectal cancer screening in Isere (France). Clinics and Research in Hepatology and Gastroenterology 2013; 37: 193—199.
  25.  Ke, K. M. et. al. The costs of centralisation: a systematic review of the economic impact of the centralisation of cancer services. European Journal of Cancer Care 2012; 21: 158–168.
  26. Katičić, M. et. al. Results of National Colorectal Cancer Screening Program in Croatia (2007-2011). World J Gastroenterol 2012; 18(32): 4300-4307.
  27. Benson, S. Victoria et. al. Colorectal cancer screening: A comparison of 35 initiatives in 17 countries. Int. J. Cancer 2008; 122: 1357–1367.
  28. Van Rossum, G. M. Leo et. al. Colorectal cancer screening comparing no screening, immunochemical and guaiac fecal occult blood tests: a cost-effectiveness analysis. Int. J. Cancer 2011; 128: 1908–1917.
  29. Walker, A. et. al. The cost of screening for colorectal cancer. Journal of Epidemiology and Community Health 1991; 45: 220-224.
  30. Sharp, L. et. al. Cost-effectiveness of population-based screening for colorectal cancer: a comparison of guaiac-based faecal occult blood testing, faecal immunochemical testing and flexible sigmoidoscopy. British Journal of Cancer 2012; 106: 805 – 816.
  31. Simoens, Steven. Health Economic Assessment: A Methodological Example. Int. J. Environ. Res. Public Health 2009; 6: 2950-2966.
  32. Mauskopf, J.A. et al. Principles of Good Practice for Budget Impact Analysis: Report if the ISPOR Task Force on Good Research Practices – Budget Impact Analysis. Value in Health 2007; 10 (5): 336-347.
  33. Rao, K. Sandhya. Challenges in the Management of Positive Fecal Occult Blood Tests. J Gen Intern Med 2009; 24(3): 356–60.
  34. Young, P. Graeme; Cole, Stephen. New Stool Screening Tests for Colorectal Cancer. Digestion 2007; 76: 26–33.
  35. Cole SR, Young GP, Esterman A, Cadd B, Morcom J: A randomized trial of the impact of new fecal hemoglobin test technologies on population participation in screening for colorectal cancer. J Med Screen 2003; 10: 117–122.
  36. Hol, L. et. al. Screening for colorectal cancer: Comparison of perceived test burden of guaiac-based faecal occult blood test, faecal immunochemical test and flexible sigmoidoscopy. European journal of cancer 2010; 46: 2059 –2066.
  37. Allison, E. James [Internet]. The Role of Fecal Occult Blood Testing in Screening for Colorectal Cancer [cited 2013-05-20]. Practical gastroenterology 2007; 3: 20-32. Available from: http://www.practicalgastro.com/pdf/June07/June07AllisonArticle.pdf;
  38. Atun, Riftat et. al. [Internet] Analysis of National Cancer Control Programmes in Europe [cited 2013-05-19]. Available from: http://spiral.imperial.ac.uk/bitstream/10044/1/4204/1/Cancer%20Control%20vf2.pdf  
  39. Shaw, Caroline et. al. [Internet] Next Steps Towards a Feasibility Study for Colorectal Cancer Screening in New Zealand: Report for the Ministry of Health [cited 2013-05-23]. Available from: https://www.google.si/url?sa=f&rct=j&url=http://www.health.govt.nz/system/files/documents/pages/next_steps_towards_a_feasibility_study_for_colorectal_cancer_screening_in_new_zealand_0.pdf&q=&esrc=s&ei=aAufUaOmBceOOPOUgbgD&usg=AFQjCNHNo1tFyhuE9ldNt-oDT4vJveU5kA; 2008.
  40. Geddie, Hannah, et. al. A prospective multiple case study of the impact of emerging scientific evidence on established colorectal cancer screening programs: a study protocol. Implementation Science 2012, 7: 51.
  41. Public Health Resource Unit [Internet]. Guidance for public health and commissioners [cited 2013-05-23]. Available from: http://www.cancerscreening.nhs.uk/bowel/publications/nhsbcsp03.pdf, 2008.
  42. Carballo F. and Munoz-Navas M. Prevention or cure in times of crisis: the case of screening for colorectal cancer. Reviesta Espanola de Enfermedades Digestivas 2012; 104 (10): 537-545.
  43. Cancer Care Ontario [Internet]. ColonCancerCheck Information for Pharmacists [cited 2013-05-23]. Available from: https://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=33442
  44. Canadian Pharmacists Association [Internet]. Ontario pharmacists participate in Canada’s first province-wide screening program for colorectal cancer Pharmacists. Canadian Pharmacists Journal / Revue des Pharmaciens du Canada 2008; 141: 159. [cited 2013-05-23].  Available from: http://cph.sagepub.com/content/141/3/159.full.pdf+html.  
  45. Van Roon H. C. et al. Are Fecal Immunochemical Test Characteristics Influenced by Sample Return Time? A Population-based Colorectal Cancer Screening Trial. The American Journal of Gastroenterology 2011. 107: 99-107.
  46. Lynge, Elsebeth et. al. Determinants of successful implementation of population-based cancer screening programmes. European journal of cancer 2012; 48: 743 –748. 

Appendices

Appendix 1: pdf10936.ORG-Appendix 1

Appendix 2: pdf10936.ORG-Appendix 2

 

Social aspects

Authors: Pseudo275 Pseudo275, Pseudo108 Pseudo108

Summary

The two systematic reviews, both published in 2012 (Vart et al. 2012 and Hassan et al. 2012) found that overall participation rate/rate of adherence resulting from their meta-analysis is significantly higher with FIT than with g-FOBT. All other socio-economical association, but not gender, and reasons for a better compliance need to be better investigated. Contextual socio-cultural variables seem to affect compliance, but ad hoc comparative cross national studies should be performed.

Introduction

The social domain deals with the impact the two tests can have on patients. The patient is considered both as an “individual” with his/her own psychology, emotion, perceptions, skills and capacities  and as a “social subject”,  an individual who is part of a community or/and a group - characterized by e.g. geographical location, religion, ethnicity, socio-economic status, age, gender etc. - with which he/she shares values, believes, experiences and culture. From an individual point of view barriers to compliance can be inconvenience of the process, embarrassment, repugnance to manipulating stool, discomfort with the procedure of the test, lack of perceived risk to develop a cancer,  fear of diagnosis, but also an individual lack of understanding and a need of information/communication provided by health providers on the technology. A specific economic status, age, ethnic group etc. can also be independent variables  for compliance with one test or another, this suggesting different screening paths for different groups or/and different ad hoc educational program. Patterns of adherence by age or sex or both, ethnicity or socioeconomic status were reported in many programs that used these tests (Vernon S. W, et al. 1997).

Social, cultural and psychological variables could affect satisfaction with and acceptance of gFOBT and FIT and thus the compliance with the tests and with their procedure (uptake, use, return). It is important to consider these aspects when designing a screening program as a higher or lower compliance in a first round population screening can affect the overall participation in the program and also the  effectiveness of the screening program.  In this context willingness of individuals to perform the screening test has as equal importance as the diagnostic accuracy  of the test, because without participation no detection is possible (Hassan et al. 2012).

Methodology

Frame

The collection scope is used in this domain.

TechnologyFecal Immunochemical Test (FIT) for colorectal cancer screening
Description

FITs use an antibody (immunoglobulin) specific to human globin, the protein component of haemoglobin, to detect fecal occult blood. Immunochemical tests have improved test characteristics compared to conventional guaiac-based tests for fecal occult blood. FIT should not be subject to interference from dietary blood and it is more specific to bleeding from the distal gastrointestinal tract. They could be analytically and clinically more sensitive and specific, Their measurement can be automated and the user can adjust the concentration at which a positive result is reported. A wide range of qualitative and quantitative tests is presently available, with varying levels of sensitivity and specificity (like Hem-SP/MagStream H, Fujirebio Inc. Japan ; OC-Sensor, Eiken Chemical Co., Tokyo, Japan;    FOB Gold, Medinostics Products Supplier; Sentinel Diagnostics SpA, Milan, Italy).

Intended use of the technologyScreening

CRC screening with faecal inmunochemical test (FIT) for detection of occult blood in the stool associated with colorectal lesions (adenomas and CRC).

The use of the test is considered under conditions of population based colorectal cancer screening, in the context of organised cancer screening programmes as recommended by the EU. Early detection and treatment of colorectal lesions before they become symptomatic has the potential to improve control of the disease, reducing morbidity and mortality associated to CRC. Early treatment of invasive lesions can be generally less detrimental for quality of life. The endoscopic removal of pre-malignant lesions also reduces the incidence of CRC by stopping the progression to cancer. Colorectal cancers and adenomatous polyps bleed has providing fecal blood haemoglobin as the biomarker of choice for current screening programmes. Stool samples could be periodically taken and analyzed for the presence of occult blood, as an early sign of colorectal lesions (adenoma or CRC).

Target condition
Adenomas, as non-malignant precursor lesions of ColoRectal Cancer (CRC).
Target condition description

CRC is the third most common in incidence and the fourth most common cause of cancer death worldwide. CRC is particularly suitable for screening. The disease is believed to develop in a vast majority of cases from non-malignant precursor lesions called adenomas. Adenomas can occur anywhere in the colorectum after a series of mutations that cause neoplasia of the epithelium. At some time , the adenoma may invade the submucosa and become malignant. Initially, this malignant cancer is not diagnosed and does not give symptoms  (preclinical phase). It can progress from localised (stage I) to metastasised (stage IV) cancer, until it causes symptoms and is diagnosed. Only 5–6% of the population actually develop CRC. The average duration of the development of an adenoma to CRC is estimated to be  at least 10 years. This long latent phase provides a window of opportunity for early detection of the disease.

Target population

Target population sex: Any. Target population age: adults and elderly. Target population group: Healthy and/or asymptomatic people.

Target population description

Adults, average risk of CRC, aged 50 years or over.

The best age range for offering gFOBT or FIT screening has not been investigated in trials. Circumstantial evidence suggests that mortality reduction from gFOBT is similar in different age ranges between 45 and 80 years .The age range for a national screening programme should at least include people aged 60 to 64 years in which CRC incidence and mortality are high and life-expectancy is still considerable. Only the FOBT for men and women aged 50–74 years has been recommended todate by the EU (Council Recommendation and the European guidelines for quality assurance in CRC screening and diagnosis).

Members of families with hereditary syndromes, previous diagnosis of CRC or pre-malignant lesions should follow specific surveillance protocols and are not included in the target population

ComparisonCRC screening with Guaiac –based fecal occult blood test (gFOBT)
Description

CRC screening with Guaiac–based fecal occult blood test (gFOBT)

The guaiac-based FOBT is still a commonly used method for detecting blood in faeces. To detect hemoglobin the test uses guaiac gum and its efficacy as a colorectal cancer screening test has been analyzed in several randomised controlled trials. The test detects the haem component of haemoglobin, which is identical across human and animal species and is chemically robust and only partially degraded during its passage through the gastrointestinal tract. gFOBTs cannot distinguish between human blood and blood residues from the diet.

Many guaiac-based tests are currently on the market (like Coloscreen, Helena Laboratories,Texas,USA; Hema-screen Immunostics Inc.; Hemoccult, Beckman Coulter Inc.; Hemoccult SENSA, Beckman Coulter Inc.; MonoHaem, Chemicon Europe Ltd; Hema-Check, Siemens PLC; HemaWipe, Medtek Diagnostics LLC)

The use of the test is considered under conditions of population based colorectal cancer screening, in the context of organised cancer screening programmes as recommended by the EU. Population-based programmes have been rolled out nationwide in several European countries. Many member states  haveestablished nationwide non-population-based programmes. Some states are planning or piloting a nationwide population-based programme. These have  adopted only FOBT, some only FIT, some a mix between FOBT and endoscopy, or only colonoscopy.

Outcomes

CUR and TEC

  • Health problems (target condition)
  • Epidemiology
  • Burden of disease
  • Target population
  • Current management of the condition
  • Features of the technology
  • Life-Cycle
  • Regulatory status
  • Utilization
  • Investments and tools required to use the technology
  • Training and information needed to use the technology

SAF

  • Colonoscopy probability of perforation
  • Colonoscopy with polypectomy probability of perforation
  • Colonoscopy probability of death following perforation
  • Probability of bleeding following colonoscopy
  • Psychological harms from false-negatives and false-positives (and generally from participating in screening program)

EFF

  • Test (FIT and gFOBT) sensitivity for adenomas
  • Test (FIT and gFOBT) sensitivity for cancer
  • Test (FIT and gFOBT) specificity for adenomas
  • Test (FIT and gFOBT) specificity for cancer 
  • Adenoma incidence (detection rates)
  • Rectal cancer incidence (detection rates)
  • Colon cancer incidence (detection rates)
  • CRC incidence (detection rates)
  • Stage distribution of detected cancers
  • Rectal cancer specific mortality
  • CRC specific mortality
  • Overall mortality
  • Life years saved

ECO:

  • Model/template for  national pilots  to assess the costs and benefits of the two alternative  technologies FIT and gFOBT  and also no-programmed-screening
  • Systematic literature search of   available models and/or economic  evaluation for screening colorectal cancer with FIT and gFOBT and no screening programme
  • Resource Utilization: Publicly funded health care payer costs (screening tests, further examinations e.g. labor, colonoscopy  and treatments and administration and organisation costs of screening programme) for FIT and gFOBT (in cooperation with ORG)
  • Cost per Case detected (average, marginal, incremental) =  intermediate outcome – optional, not decided yet (relevant for deciding how often a test should be carried out and what are the incremental costs for a “new” detected case
  • Indirect Costs: not for the Core modell (should be decided later on)
  • Test accuracy: from SAF
  • Cost effectiveness analysis: HRQoL measures (both generic and context specific) (EFF and SAF for help, own Lit.research), ICER

 ORG:

  • Responsiveness of target population to invitation
  • Invitation-reminder system
  • Competence of human resources – health professionals
  • Investments needed (material,equipment)
  • Costs of using both tests (FIT, gFOBT)
  • Timeliness of results and future phases
  • Use of tools for process monitoring (completed check lists)
  • Model for Budget Impact Analysis from perspective of the payer

SOC

  • Compliance with the tests (FIT, gFOBT)
  • Anxiety and any psychological effects of using  one test or another
  • Information, counseling, communication (quality of) for the use of tests
  • Satisfaction  
  • Quality of life
  • Equity of access

LEG

  • Information as baseline for an informed consent
  • Harms or inequities that can be taken to court

Assessment elements

TopicIssue RelevantResearch questions or rationale for irrelevance
H0001Major life areasWhich social areas does the use of the technology influence?yesWhich social areas does the use of FIT and gFOBT influence?
H0002Major life areasWho are the important others that may be affected, in addition to the individual using the technology?yesWho are the important others that may be affected, in addition to the individual using gFOBT and FIT?
H0004Major life areasWhat kind of changes may the use of the technology generate in the individual's role in the major life areas?noWe do not think that the screening of crc will provide major role-changes. This could be relevant with a positive screening result, but not for the screening participation.
H0003Major life areasWhat kind of support and resources are needed for the patient or citizen as the technology is introduced?noThis part is better treated in Organisational and costs domains.
H0010Major life areasWhat kind of social support and resources are needed for the providers as the technology is introduced?noBetter to be trated in the organisational domain.
H0011Major life areasWhat kinds of reactions and consequences can the introduction of the technology cause at the overall societal level?noIn many countries the FOBT or FIT tests are already used as screening. There are no experiences about any reactions or consequences on the overall societal level.
H0012IndividualAre there factors that could prevent a group or persons to participate?yesAre there factors that could prevent a group or persons to participate?
H0006IndividualHow do patients, citizens and the important others using the technology react and act upon the technology?yesHow do patients, citizens and the important others using FIT or gFOBT react and act upon them?
H0005IndividualWhat kind of physical and psychological changes does the implementation and use of the technology bring about and what kind of changes do patients or citizens expect?noRelevant if we had to focus on the whole screening process. Further gFOBT and FIT do not cause harms.
H0007CommunicationWhat is the knowledge and understanding of the technology in patients and citizens?yesWhat is the knowledge and understanding of FIT or gFOBT in patients and citizens?
H0008CommunicationHow do patients and citizens perceive the information they receive or require about the technology?yesHow do patients and citizens perceive the information they receive or require about FIT and gFOBT?
H0009CommunicationWhat influences patients’ or citizens’ decisions to use the technology?yesWhat influences patients’ or citizens’ decisions to use FIT or gFOBT?
H0013CommunicationWhat are the social obstacles or prospects in the communication about the technology?yesWhat are the social obstacles or prospects in the communication about gFOBT and FIT?

Methodology description

Domain frame

We will focus on the social, cultural and psychological variables that can affect the uptake – use and return of gFOBT and FIT - and will look for studies aimed at collecting evidence that tried to verify those associations or at collecting more in depth information on psychological barriers to the use of the two tests.

For some research questions we could not find any evidence, and this is highlighted in each related result card. For other research questions we detected an intra-domain overlap, so we chose to subsume evidence in only one of the two research questions and result cards that we had judged to overlap (see each single result cards for more information on intra-domain overlapping).

We could find evidence for 4 research questions/assessment elements out of the 8 we initially had selected. Result cards we filled are described below.

The first is SOC7 - AE H0001 (Which social areas does the use of FIT and gFOBT influence?). In this Result card we included evidence on how characteristics of the tests and their procedure are perceived by individual in his/her daily life (e.g. more or less burdensome according to impact on individual’s major life areas such as lifestyle and daily activities).

SOC14 - AE H0009 (What influences patients or citizens decisions to use FIT or gFOBT?) is a question that points out how societal influences can affect compliance and participation. In this result card we summarized evidence about influence of social identity (e.g. ethnicity) and of the group to which individual belongs (defnied by age, or socio-economic status, gender etc.) on compliance and participation.

The SOC10 – AE H0006 (How do patients, citizens and the important others using FIT or gFOBT react and act upon them?)  contains the evidence on different compliance and participation rates with one test or the other as it is also about satisfaction (thus compliance and participation) of  citizens using the technology.

SOC11- AE H0007 (What is the knowledge and understanding of FIT or gFOBT in patients and citizens?) is a result card were we report studies that provide information on understanding of the technology by patients related to communication or information provided by health care providers (information leaflets, invitation letters). This research question (and result card) overlaps with ORG domain, where – at least in the case of a screening program - more information can probably be found.

 

Information sources

A specific search for the social domain was conducted in the traditional databases. No mix with the literature of other domains was done. For the Search Strategy see Appendix 1.

Inclusion criteria:

We included all secondary and primary studies that where about target population (50-64 years and 65+ years; male and female; healthy/asymptomatic population; compared FIT vs gFOBT and measured/dealt with outcomes related to the social domain (e.g. compliance , participation rates associated with socio-demographical variables etc.). We included RCTs and observational studies and qualitative social studies, also if related to just one of the two technologies at stake.

A list of all the studies we selected for the full text reading is provided in the Appendix 2, with reasons for exclusion.

Quality assessment tools or criteria

As a measurement tool to assess the methodological quality of systematic reviews we used AMSTAR (at least 6 score). For primary studies we used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS). See appendix 4 and 5 for both instruments applied to selected primary and secondary studies.

 

Analysis and synthesis

All abstracts from the domain specific literature search were screened by both ALS and IW, on the basis of the previously agreed inclusion criteria. Disagreement on inclusions were discussed. We read in double full articles of all the selected records, and extracted information/data from them on the basis of each single assessment elements using ad hoc extraction sheets. After this we refined which study had to be included and, for each of them, and independent data extraction was performed.

 

When a systematic review was relevant for answering  a specific result card’s question and was judged of good quality, this was our main source of information. To this we added information and data from the studies we had selected that were not included in the systematic review itself. Not all the studies and systematic reviews had relevant information and data for each single result card/assessment element. When studies were relevant, data and information from each of them where extracted and reported in the relevant result card.

 

Overall results

 

Included studies

 

Elevent 11records (Birkenfeld et al. 2011, Cole et al. 2003, Federici et al. 2005, Hassan et al. 2012, Hawley et al. 2008, Hol 2010a and Hol 2010b, Hughes et al. 2005, Levi et al. 2011, van Rossum et al. 2010, Vart et al. 2012) were included in the analysis of the social domain. Nine (9) primary studies (8 RCTs and one prospective observational study) and 2 systematic reviews (Hassan et al. 2012, Vart 2012). The complete list of all included studies and extraction of their characteristics can be found in Appendix 3. No qualitative social studies were included.

 

The two studies by Hol published in 2010 refer to the same population based trial, but describe results of different “line of research” made on the same cohort.  Both were included as they provided evidence for different result cards (compliance and socio-economic factors affecting it).

The two Israeli studies published in 2011 (Birkenfeld et al. and Levi et al) are based on the same population, but as  above, the Birkenfeld at al. article aimed at verifying if socio economic status impacted on compliance within the same population-based study described in Levi et al.). We included both Hol’s and both Levi’s and Birkenfeld as, although based on same population, they reported results on different social outcomes we included in our focus.

 

 

 

 

 

Year of publication

The studies were published in 2003 (Cole et al., 2003), 2005 (Federici et al 2005, Hughes et al 2005), 2008 (Hawley et al 2008), 2010 (Hol et al 2010a and Hol et al. 2010b, van Rossum 2010), 2011 (Birkenfeld et al. 2011, Levi et al. 2011), and 2012 (Hassan et al. 2012, Vart et al. 2012). None of the studies had a huge gap between study conduction and study publication.

 

Country

Three of the primary studies were from the Netherlands (Hol et al. 2010a and Hol et al. 2010b, van Rossum et al. 2010) two of the studies were from Israel (Birkenfeld 2011, Levi 2011 but same population from which they published two articles on different outcomes), 1 from the USA (Hawley 2008,), two from Australia (Cole  2003, Hughes 2005) and one from Italy (Federici 2005). The two systematic reviews (Hassan 2012, Vart 2012) were included studies from Australia, Italy, Netherlands, USA, Israel. Hassan 2012 included 14 studies in their meta-analysis, 4double with our search results (Federici 2005, van Rossum 2008, Hoffmann 2010, Hol 2010, Levi 2011,), whereas two included in Hassan were excluded by us (Segnan 2007 and Quintero 2012 due to no comparison of FIT versus gFOBT). Vart included 7 studies in their metanalysis, among them we did not include just Hoffman due to target population (male and veterans), while Hol 2009 was not retrieved with our search strategy, which on the other hand included two other Hol’s studies both published in 2010, which are based on the same cohort of healthy Dutch people.

 

Funding

Ten studies provided information about funding of the research, in two studies the funding was unclear or not mentioned (Hawley 2008, Federici 2005). Three studies reported a funding from companies (Birkenfeld 2011, Cole 2003, Levi 2011), four studies reported a funding by official organisations (Hassan 2012, Hol 2010a, van Rossum 2008, Vart 2012) and two studies (Hol 2010b, Hughes 2005) reported mixed official and company funding.

 

 

Official funding

Funding from companies

Birkenfeld, et al. 2011

 

Eiken Japan provided the OC-MICROTM instrument, reagents and partial financial support for administration.

Cole, et al. 2003

 

Grant support: Hemoccult SENSA and FlexSure OBT cards

were purchased from Beckman Coulter Inc. (Palo Alto CA,

USA). Enterix Inc. (Portland ME, USA) provided InSure test

kits. Grants from the Bushell Foundation and Enterix Inc.

provided part support for salaries (SC, BC).

Federici et al. 2005

Not applicable

Not applicable

Hawley et al. 2008

Unclear

Unclear

Hol 2010a (44)

This trial was funded by the Dutch Cancer Society (EMCR

2006-3673), and the Dutch Ministry of Health, Health Care Prevention

Program–Implementation (ZonMw 2006-5877).

 

Hol 2010b (46)

This trial was funded by the Dutch Cancer Society (EMCR 2006-3673), the

Dutch Ministry of Health, Health Care Prevention Program–Implementation (ZonMw

2006-5877),

Olympus Medical Systems Europe GmbH, Hamburg, Germany and Eiken

Chemical Co., Tokyo, Japan.

Hughes et al.  2005

This research was funded by Queensland Health. The pathology laboratory at Townsville General Hospital, which provided analysis of Hemoccult-II kits at a greatly reduced fee.

In addition, funding was subsidised by Enterix (Inc), which made the !nform FOBT kit and its analysis available at a highly discounted rate.

Levi et al. 2011

 

Eiken Japan provided the OC-MICROTM instrument, reagents and partial financial support for administration.

Van Rossum et al. 2008

Netherlands organization for Health Research and Development (ZonMW: number 50-50115-98-060, project 63000004)

 

Hassan et al.  2012

This study was partially funded by the Italy Ministry of Health, through a project coordinated by the Agenzia Nazionale per i Servizi Sanitari and conducted

by Laziosanità: ‘Strumenti e metodi per il governo dei processi di innovazione tecnologica, clinica ed organizzativa nel SSN – Un sistema integrato di ricerca’,

 sub-project ‘Analysis of the impact of professional involvement in evidence generation for the HTA process’ grant no. I85J07000080001.

 

Vart et al. , 2012

This research was funded via studentship provided by The Guildford Tumour Screening (G.U.T.S) charity for part fulfilment of the degree PhD Health Psychology at the University of Surrey

 

 

 

Trial registration (RCTs)

One study provided a trial registration number (van Rossum 2008).

 

Basic population data

 

SYSTEMATIC REVIEWS

Vart 2012

 

Number of included studies was 7;

(Cohorts ranged from 1818 (Cole 2003) to 20623 (van Rossum 2008).

50+

n.a.

screening population

n.a.

n.a.

population based program setting

FIT

gFOBT

Hassan 2012

Five studies compared g-FOBT with FIT, including 59 729 randomised subjects

 

Number of included studies was 5

50-74 (4x), 50-75 (4x); 55-64 (3x); 50-54/65-69 (1x); 50-80 (1x); 50-69 (1x)

male 49.5%; female 50.5% (own calculation of all studies included in the meta analysis)

no exclusions

n.a.

n.a.

population screening

FIT/gFOBT/endoscopy

FIT/gFOBT/endoscopy

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

PRIMARY STUDIES

Birkenfeld 2011

16132 [10668 (gFOBT) + 5464 (FIT)]

60-74

43,1% male; 56,9% female

asymptomatic

10,8% immigrants

34% high SES, 36,6% medium SES, 29,4% low SES

Israel

primary care clinic registrees, setting population-based like

FIT

gFOBT

Cole 2003

1818 (3 groups of each 606)

 

 

 

 

 

 

 

 

 

50-69

 

 

 

 

 

 

 

 

 

 

 

49,5% male, 50,5% female (own calculation of table 1)

no exclusions

Exposure of this population to screening was low by US standards and prior participation in screening had been less than 20%.

Exposure of this population to screening was low by US standards and prior participation in screening had been less than 20%.

Australia

population screening

FIT

 

 

 

 

 

 

 

 

 

 

gFOBT

 

 

 

 

 

 

 

 

 

 

Federici 2005

7320

50-74

Guaiac 46.9% men  FIT 45.8% men

average risk

no

no

Italy

population screening

FIT

gFOBT

Hawley 2008

220

50-80

not specified, proportion controlled in the analysis

asymptomatic

74 white, 60 Africans, 78 Hispanic

 

USA, Michigan

None. Diverse hypothetical scenarios. Southern urban

FOBT, COL, SIG, FIT, V-COL

 

Hol 2010a

852

50–74

45.3% male (FOBT), 50.6% male (FIT), 50.7% (FS)

asymptomatic

5% non Cuacasian

no

NL

population screening

FIT

FOBT, FS

Hol2010b

15111

50-74

participation OR for Women 1.1 (0.9 to 1.4) (FOBT)  1.3 (1.1 to 1.4)(FIT) 0.9 (0.8 to 1.0)(FS)

asymptomatic

n.a.

n.a.

NL

population screening

FIT

FOBT, FS

Hughes 2005

3358

50-74

51.2% female

asymptomatic

no

no

Australia

population screening

FIT

FOBT, FS

Levi 2011

12,539 (4,657 FIT; 7,880 G-FOBT)

mean age FIT: 60.4, mean age FOBT 61.3

45.4% male for FIT, 42.6% male for FOBT

asymptomatic

n.a.

SES controlled

Israel

population screening

FIT

FOBT

van Rossum 2008

Out of 20.623 people the test was sent to 10.993 tests were returned

50-75 years (50.4% with GFOBT and 51.7% with IFOBT aged < 60)

47.8% (GFOBT) and 48.8% (IFOBT) male

asymptomatic

n.a.

n.a.

Netherlands

population based program setting

FIT

gFOBT

 

 

Result cards

Major life areas

Result card for SOC7: "Which social areas does the use of FIT and gFOBT influence?"

View full card
SOC7: Which social areas does the use of FIT and gFOBT influence?
Method
Result

Importance: Important

Transferability: Partially

Result card for SOC8: "Who are the important others that may be affected, in addition to the individual using gFOBT and FIT?"

View full card
SOC8: Who are the important others that may be affected, in addition to the individual using gFOBT and FIT?
Method
Frame
Result
Comment

Importance: Unspecified

Transferability: Unspecified

Communication

Result card for SOC11: "What is the knowledge and understanding of FIT or gFOBT in patients and citizens?"

View full card
SOC11: What is the knowledge and understanding of FIT or gFOBT in patients and citizens?
Method
Result
Comment

Importance: Important

Transferability: Partially

Result card for SOC12: "How do patients and citizens perceive the information they receive or require about FIT and gFOBT?"

View full card
SOC12: How do patients and citizens perceive the information they receive or require about FIT and gFOBT?
Method
Frame
Result
Comment

Importance: Unspecified

Transferability: Unspecified

Result card for SOC14: "What influences patients’ or citizens’ decisions to use FIT or gFOBT?"

View full card
SOC14: What influences patients’ or citizens’ decisions to use FIT or gFOBT?
Method
Result
Comment

Importance: Important

Transferability: Partially

Result card for SOC15: "What are the social obstacles or prospects in the communication about gFOBT and FIT?"

View full card
SOC15: What are the social obstacles or prospects in the communication about gFOBT and FIT?
Method
Result
Comment

Importance: Unspecified

Transferability: Unspecified

Individual

Result card for SOC6: "Are there factors that could prevent a group or persons to participate?"

View full card
SOC6: Are there factors that could prevent a group or persons to participate?
Method
Frame
Result
Comment

Importance: Unspecified

Transferability: Unspecified

Result card for SOC10: "How do patients, citizens and the important others using FIT or gFOBT react and act upon them?"

View full card
SOC10: How do patients, citizens and the important others using FIT or gFOBT react and act upon them?
Method
Result

Importance: Unspecified

Transferability: Unspecified

Discussion

The two systematic reviews, both published in 2012 (Vart et al. 2012 and Hassan et al. 2012) found that overall participation rate/rate of adherence resulting from their meta-analysis is significantly higher with FIT than with g-FOBT.  Hassan et al. included two more studies (Cole et al 2003 and Hughes et al. 2005), this may be due to different search strategy, but this does not change final result.

Both studies’ authors highlight that inter-study heterogeneity in their meta-analysis is higher, but is related only to one included study, Levi et al (2011). The exclusion of Levi et al resulted in a reduction in the  I2 e  from 96% to to 0% (Hassan et al.2012). Result of the Israeli population based study show that contextual socio-cultural and/or geographical variables might affect compliance.

Reasons for FIT outperforming gFOBT (or the opposite, in the case of Isreali studies) in compliance rate needs to be better investigated via qualitative studies and quantitative designs that confirm any interpretative hypothesis. For the moment all we found in the literature are conjectures and authors’ opinions.  Socio-demographical and ethnicity variables seem to have a part in affecting compliance with one test or another, but more research seem to be needed to confirm this.

In some cases, such as socio economic status, studies give, , conflicting results. In the Australian study by Cole et al, socioeconomic status showed not to be a confounding factor, while in Birkenfeld this association was verified. More evidence is also needed to evaluate the importance of age as studies gave inconsistent result, both in term of overall compliance to screening and in terms of compliance broken down by age groups when comparing FIT and gFOBT.  On the other side, as regard to gender, results of quite all studies that focused on this variable  (Hughes, 2005; Hol, van Leerdam M.E 201; Birkenfeld 2011) showed that female gender were independent predictors of increased attendance/compliance in both arms. The study by Hughes et al. 2005, which is about the “intention to participate” (scenarios) seem to show differences among different ethnic group in preferring FIT versus gFOBT and other CRC screening methods, but yet this association should need further evidence.

References

Birkenfeld, S., et al. (2011). "Factors affecting compliance in faecal occult blood testing: a cluster randomized study of the faecal immunochemical test versus the guaiac faecal occult test." J Med Screen 18(3): 135-141.

Cole, S. R., et al. (2003). "A randomised trial of the impact of new faecal haemoglobin test technologies on population participation in screening for colorectal cancer." J Med Screen 10(3): 117-122.

Federici, A., et al. (2005). "The immunochemical faecal occult blood test leads to higher compliance than the guaiac for colorectal cancer screening programmes: a cluster randomized controlled trial." J Med Screen 12(2): 83-88.

Hassan, C., et al. (2012). "Meta-analysis: adherence to colorectal cancer screening and the detection rate for advanced neoplasia, according to the type of screening test." Aliment Pharmacol Ther 36(10): 929-940.

Hawley, S. T., et al. (2008). "Preferences for colorectal cancer screening among racially/ethnically diverse primary care patients." Med Care 46(9 Suppl 1): S10-16.

Hol, L., et al. (2010). "Screening for colorectal cancer: comparison of perceived test burden of guaiac-based faecal occult blood test, faecal immunochemical test and flexible sigmoidoscopy." Eur J Cancer 46(11): 2059-2066.

Hol, L., et al. (2010). "Screening for colorectal cancer: randomised trial comparing guaiac-based and immunochemical faecal occult blood testing and flexible sigmoidoscopy." Gut 59(1): 62-68.

Hughes, K., et al. (2005). "Guaiac versus immunochemical tests: faecal occult blood test screening for colorectal cancer in a rural community." Aust N Z J Public Health 29(4): 358-364.

Levi, Z., et al. (2011). "A higher detection rate for colorectal cancer and advanced adenomatous polyp for  screening with immunochemical fecal occult blood test than guaiac fecal occult blood test, despite lower compliance rate. A prospective, controlled, feasibility study." Int J Cancer 128(10): 2415-244.

Vernon, S.W. Participation in Colorectal Cancer Screening: a review , Journal of the National Cancer Institute , Vol. 89, No. 19, 1997.

 

Appendices

Domain appendices
APPENDIX 1

SERACH STRATEGY

SOC domain: compliance, acceptability, satisfaction

MEDLINE

 

Colorectal neoplasms (MESH term)

All terms

Neoplasms, Colorectal

Colorectal Neoplasm

Neoplasm, Colorectal

Colorectal Tumors

Colorectal Tumor

Tumor, Colorectal

Tumors, Colorectal

Colorectal Carcinoma

Carcinoma, Colorectal

Carcinomas, Colorectal

Colorectal Carcinomas

Colorectal Cancer

Cancer, Colorectal

Cancers, Colorectal

Colorectal Cancers

OR

(Colorect*  OR Colon * OR rect* or anal* or anus* OR intestin* or bowel*)

 

AND

 

 (carcinoma* OR neoplasm* OR adenocarcinom* OR cancer* OR tumor* OR sarcom* OR polyp* OR adenoma* OR neoplasia)

AND

Test*  (All Fiedls)

OR

Screening*(All Fields)

AND

 

“Faecal immunochemical test*”

 

Or

Fit

OR

(immunohistochem* or immunochem* or immunol*)

 

AND

 

(fecal immunochemical test* or faecal immunochemical test* or fecal immunochemistry test* or faecal immunochemistrytest*

Or “Screening test*”

Or “occult blood test*”

OR

 ColoScreen*  Or  Hema-Screen* or Hemdetect* or Hemoccult* or SENSA* or  Hema-Check* or  hemoCARE*or  Peroheme* or ColoCare* or  Lifeguard* or Fecatwin* or HemaW ipe* Or Instaccult* or Monohaem* or Okokit* or Seracult* or Dencoccult* or ColoRectal* or Early detector* Or Fe Cult* or Feca EI A* or Hemo FEC* or Hexagon* or SureScreen* or Hemaprompt* or Hemdetect* or Camco PAK* or  Colocheck* or Cecogenics* or  Hemates t* or

Dencocult* or Fecatest* or Hemofecia* or Quick-CULT*

2 OR “OC-sensor test*” OR “Insure fit” OR  “HemeSelect”, “FlexSure OBT, and “OC-Sensor Micro FIT*”

AND

compliance OR adherence OR acceptance OR acceptability OR participation OR preference OR preferences OR invitation OR 'perception  OR perceptions

OR Non-Adherence

OR attitude*

OR Satisfaction

OR

Patient compliance MESH term

Adults, ENGLISH, All fields, Article, e review

 

EMBASE

 

Colorectal Carcinoma

 (EMTREE TERM)

 

OR

“Colorectal Carcinoma”.exp

 

OR

(Colorect*  OR Colon * OR rect* or anal* or anus* OR intestin* or bowel*) .exp

 

AND

 

 (carcinoma* OR neoplasm* OR adenocarcinom* OR cancer* OR tumor* OR sarcom* OR polyp* OR adenoma* OR neoplasia).exp

AND

Test*  (Exp)

OR

Screening*(Exp)

AND

“Faecal immunochemical test*”

 

Or

Fit

OR

(immunohistochem* or immunochem* or immunol*).exp

 

AND

 

((fecal immunochemical test* or faecal immunochemical test* or fecal immunochemistry test* or faecal immunochemistrytest*).exp

Or “Screening test*”

Or “occult blood test*”)

OR

 ColoScreen*  Or  Hema-Screen* or Hemdetect* or Hemoccult* or SENSA* or  Hema-Check* or  hemoCARE*or  Peroheme* or ColoCare* or  Lifeguard* or Fecatwin* or HemaW ipe* Or Instaccult* or Monohaem* or Okokit* or Seracult* or Dencoccult* or ColoRectal* or Early detector* Or Fe Cult* or Feca EI A* or Hemo FEC* or Hexagon* or SureScreen* or Hemaprompt* or Hemdetect* or Camco PAK* or  Colocheck* or Cecogenics* or  Hemates t* or

Dencocult* or Fecatest* or Hemofecia* or Quick-CULT*

2 OR “OC-sensor test*” OR “Insure fit” OR  “HemeSelect”, “FlexSure OBT, and “OC-Sensor Micro FIT*”

AND

compliance OR adherence OR acceptance OR acceptability OR participation OR preference OR preferences OR invitation OR 'perception  OR perceptions OR satisfaction

OR Non-Adherence

OR

Patient compliance EMTREE term

OR

Patient attitude EMTREE

(“article” OR “review” OR “short survey”) Limits: Humans

Cochrane Library: CDSR, DARE, HTA database, CENTRAL search strategy

 

Colorectal neoplasms (MESH term)

All terms

 

OR

(Colorect*  OR Colon * OR rect* or anal* or anus* OR intestin* or bowel*) ti,ab,kw

 

AND

 

 (carcinoma* OR neoplasm* OR adenocarcinom* OR cancer* OR tumor* OR sarcom* OR polyp* OR adenoma* OR neoplasia). ti,ab,kw

AND

Test* ti,ab,kw

OR

Screening* ti,ab,kw

AND

“Faecal immunochemical test*”.ti,ab,kw

 

Or

Fit

OR

(immunohistochem* or immunochem* or immunol*).ti,ab,kw

 

AND

 

(fecal immunochemical test* or faecal immunochemical test* or fecal immunochemistry test* or faecal immunochemistrytest*).ti,ab,kw

Or

 “Screening test*”.ti,ab,kw

Or

 “occult blood test*”.ti,ab,kw

OR

 (ColoScreen*  Or  Hema-Screen* or Hemdetect* or Hemoccult* or SENSA* or  Hema-Check* or  hemoCARE*or  Peroheme* or ColoCare* or  Lifeguard* or Fecatwin* or HemaW ipe* Or Instaccult* or Monohaem* or Okokit* or Seracult* or Dencoccult* or ColoRectal* or Early detector* Or Fe Cult* or Feca EI A* or Hemo FEC* or Hexagon* or SureScreen* or Hemaprompt* or Hemdetect* or Camco PAK* or  Colocheck* or Cecogenics* or  Hemates t* or

Dencocult* or Fecatest* or Hemofecia* or Quick-CULT*

2 OR “OC-sensor test*” OR “Insure fit” OR  “HemeSelect”, “FlexSure OBT, and “OC-Sensor Micro FIT*”).ti,ab,kw

AND

compliance OR adherence OR acceptance OR acceptability OR participation OR preference OR preferences OR invitation OR 'perception  OR perceptions OR Non-Adherence OR Attitude OR attitudes OR satisfaction

 

(“article” OR “review” OR “short survey”) Limits: Humans

 

Other consulted databases (free terms research)

 

DARE all databases; Agency for Healthcare Research and Quality (AHRQ); Australian Safety and Efficacy Register of New Interventional Procedures  (ASERNIP-S) , Health Canada; International Network of Agencies for Health Technology Assessment (INAHTA); Medical Services Advisory Committee (MSAC); National Coordinating Centre for Health Technology Assessment (NCCHTA);  National Horizon Scanning Centre; National Institute for Health and Clinical Excellence (NICE); NHS Quality Improvement Scotland (NHS QIS); Clinicaltrials.gov, Cancer.gov, Trip Database.

 

 
 
 
 
 
APPENDIX 2

List of included and excluded studies and reasons for exclusions due to the inclusion-exclusion criteria

Reference fit compliance

Target population (adults_19-64 years and elderly _65+ years;  male and female. Healthy and/or asymptomatic people),

It is about FIT or/and gFOBT

Measure/deal with outcomes that are related to the social domain (e.g. compliance with one test or the other, capacity to understand information on the two tests, etc.)

Type of study: quantitative studies_experimental or observational AND qualitative studies

1.       Akram, S., et al. (2012). "Yield of fecal immunochemical test in detection of colorectal cancer and advanced neoplasia in veteran population at dayton va medical center." Am. J. Gastroenterol. 107: S810.

 

 

NO

 

2.       Aschele, C., et al. (2009). "Chemotherapy for operable and advanced colorectal cancer." Cancer Treat Rev 35(6): 509-516.

NO

 

 

 

3.       Bampton, P. A., et al. (2005). "Interval faecal occult blood testing in a colonoscopy based screening programme detects additional pathology." Gut 54(6): 803-806.

NO

 

 

 

4.       Bhattacharya, R., et al. (2010). "Comparison of advanced noninvasive techniques to screen colorectal cancer: Fecal immunochemical test vs. fecal DNA; A cos-effectiveness study." Value Health 13(7): A265.

 

NO

 

 

5.       Birkenfeld, S., et al. (2011). "Factors affecting compliance in faecal occult blood testing: a cluster randomized study of the faecal immunochemical test versus the guaiac faecal occult test." J Med Screen 18(3): 135-141.

 

 

 

 

6.       Boemo, C., et al. (2012). "Short-term outcomes and cost evaluation of the first two rounds of a colorectal cancer screening programme based on immunochemical faecal occult blood test in a northern italian province." Endoscopy 44(4): 441.

 

NO

 

 

7.       Browne, S., et al. (2011). "Patients' needs following colorectal cancer diagnosis: where does primary care fit in?" Br J Gen Pract 61(592): e692-699.

NO

 

 

 

8.       Byers, T. (2011). "Examining stools for colon cancer prevention: what are we really looking for?" Cancer Prev Res (Phila) 4(10): 1531-1533.

 

 

 

NO

9.       Calvet, X., et al. (2002). "Evaluation of Helicobacter pylori diagnostic methods in patients with liver cirrhosis." Aliment Pharmacol Ther 16(7): 1283-1289.

NO

 

 

 

10.    Castiglione, G., et al. (1996). "Immunochemical vs guaiac faecal occult blood tests in a population-based screening programme for colorectal cancer." Br J Cancer 74(1): 141-144.

 

 

NO

 

11.    Cavallaro, L. G., et al. (2011). "Screening for colorectal cancer (CRC) from the first three rounds (2005-2011) in an Italian north-eastern district (ULSS-1) with a high adherence rate: Preliminary results." Dig. Liver Dis. 43: S185-S186.

 

NO

 

 

12.    Cha, J. M., et al. (2011). "Telephone reminder call in addition to mailing notification improved the acceptance rate of colonoscopy in patients with a positive fecal immunochemical test." Dig Dis Sci 56(11): 3137-3142.

NO

 

 

 

13.    Ching, J. Y. L., et al. (2012). "Mailing invitations for colorectal cancer (CRC) screening programme in Hong Kong: A comparison between private and public estates." J. Gastroenterol. Hepatol. 27: 200.

 

NO

 

 

14.    Ching, J. Y. L., et al. (2012). "Compliance with fecal immunochemical tests for colorectal cancer screening: A prospective cohort study." J. Gastroenterol. Hepatol. 27: 197.

The fulltext was not available

15.    Cole, S. R., et al. (2007). "An advance notification letter increases participation in colorectal cancer screening." J Med Screen 14(2): 73-75.

 

NO

 

 

16.    Cole, S. R., et al. (2009). "A faecal immunochemical test for haemoglobin using a single stool sample is effective for detecting significant colorectal neoplasia." J. Gastroenterol. Hepatol. 24: A239.

 

 

NO

 

17.    Cole, S. R., et al. (2003). "A randomised trial of the impact of new faecal haemoglobin test technologies on population participation in screening for colorectal cancer." J Med Screen 10(3): 117-122.

 

 

 

 

18.    Crotta, S., et al. (2012). "High rate of advanced adenoma detection in 4 rounds of colorectal cancer screening with the fecal immunochemical test." Clin Gastroenterol Hepatol 10(6): 633-638.

 

NO

 

 

19.    Crotta, S., et al. (2012). "Interval cancers in a colorectal cancer population screening fit-based: Preliminary result of two rounds." Dig. Liver Dis. 44: S198-S199.

NO

 

 

 

20.    Daly, J. M., et al. (2010). "Mailed fecal-immunochemical test for colon cancer screening." J Community Health 35(3): 235-239.

 

NO

 

 

21.    De Haan, M. C., et al. (2012). "Does CT colonography have a role for population-based colorectal cancer screening?" Eur Radiol 22(7): 1495-1503.

 

NO

 

 

22.    Denis, B., et al. (2007). "Short term outcomes of the first round of a pilot colorectal cancer screening programme with guaiac based faecal occult blood test." Gut 56(11): 1579-1584.

 

NO

 

 

23.    Denters, M., et al. (2010). "Equal advanced neoplasia detection rates in first and second round of an fecal immunochemical test based colorectal cancer screening program." Gastroenterology 138(5): S186.

 

 

NO

 

24.    Denters, M., et al. (2010). "Participation rate in a second round of fecal immunochemical test based screening decreases due to low response rates among previous non-responders and first-time invitees." Gastroenterology 138(5): S186.

NO

 

 

 

25.    Denters, M. J., et al. (2012). "A feces collection paper does not enhance participation in a fecal immunochemical test-based colorectal cancer screening program: Randomized clinical trial." Eur.J. Cancer Prev.

 

NO

 

 

26.    Denters, M. J., et al. (2013). "Involvement of previous non-participants cannot fully compensate for lower participation in a second round of FIT-screening." Cancer Epidemiol.

 

NO

 

 

27.    Desoubeaux, N., et al. (1997). "[Mass screening of colorectal cancer by general practitioners in France: what is  the real target population?]." Gastroenterol Clin Biol 21(10): 760-763.

NO

 

 

 

28.    Ealey, J., et al. (2011). "Patients' perspectives on immunochemical fecal occult blood test (I-FOBT or FIT): Not your father's FOBT." Cancer Epidemiol. Biomarkers Prev. 20(10).

 

 

 

 

29.    Eisinger, F., et al. (2011). "Cancer survivors: familial risk perception and management advice given to their relatives." Fam Cancer 10(1): 147-155.

NO

 

 

 

30.    Federici, A., et al. (2005). "The immunochemical faecal occult blood test leads to higher compliance than the guaiac for colorectal cancer screening programmes: a cluster randomized controlled trial." J Med Screen 12(2): 83-88.

 

 

 

 

31.    Fenocchi, E., et al. (2006). "Screening for colorectal cancer in Uruguay with an immunochemical faecal occult blood test." Eur J Cancer Prev 15(5): 384-390.

 

NO

 

 

32.    Fraser, C. G., et al. (2007). "Evaluation of a card collection-based faecal immunochemical test in screening for colorectal cancer using a two-tier reflex apprTan, Woach." Gut 56(10): 1415-1418.

 

 

NO

 

33.    Graser, A., et al. (2009). "Comparison of CT colonography, colonoscopy, sigmoidoscopy and faecal occult blood tests for the detection of advanced adenoma in an average risk population." Gut 58(2): 241-248.

 

 

NO

 

34.    Grazzini, G., et al. (2000). "Colorectal cancer screening by fecal occult blood testing: results of a population-based experience." Tumori 86(5): 384-388.

 

 

NO

 

35.    Greenwald, B. (2005). "A comparison of three stool tests for colorectal cancer screening." Medsurg Nurs 14(5): 292-299; quiz 300.

 

 

 

NO

36.    Hall, M. J., et al. (2011). "Effects of a decision support intervention on decisional conflict associated with microsatellite instability testing." Cancer Epidemiol Biomarkers Prev 20(2): 249-254.

 

NO

 

 

37.    Harden, E., et al. (2011). "Exploring perceptions of colorectal cancer and fecal immunochemical testing among African Americans in a North Carolina community." Prev Chronic Dis 8(6): A134.

no

 

 

 

38.    Hassan, C., et al. (2011). "Cost effectiveness and projected national impact of colorectal cancer screening in France." Endoscopy 43(9): 780-793.

 

 

NO

 

39.    Hassan, C., et al. (2012). "Meta-analysis: adherence to colorectal cancer screening and the detection rate for advanced neoplasia, according to the type of screening test." Aliment Pharmacol Ther 36(10): 929-940.

 

 

 

 

40.    Hawley, S. T., et al. (2008). "Preferences for colorectal cancer screening among racially/ethnically diverse primary care patients." Med Care 46(9 Suppl 1): S10-16.

 

 

 

 

41.    Heitman, S. J., et al. (2010). "Colorectal cancer screening for average-risk North Americans: an economic evaluation." PLoS Med 7(11): e1000370.

 

 

NO

 

42.    Hillyer, G. C., et al. (2011). "Feasibility and efficacy of pairing fecal immunochemical testing with mammography for increasing colorectal cancer screening among uninsured Latinas in northern Manhattan." Prev Med 53(3): 194-198.

NO

 

 

 

43.    Hoffman, R. M., et al. (2010). "Colorectal cancer screening adherence is higher with fecal immunochemical tests than guaiac-based fecal occult blood tests: a randomized, controlled trial." Prev Med 50(5-6): 297-299.

NO

 

 

 

44.    Hol, L., et al. (2010). "Screening for colorectal cancer: comparison of perceived test burden of guaiac-based faecal occult blood test, faecal immunochemical test and flexible sigmoidoscopy." Eur J Cancer 46(11): 2059-2066.

 

 

 

 

45.    Hol, L., et al. (2012). "Uptake of faecal immunochemical test screening among nonparticipants in a flexible sigmoidoscopy screening programme." Int J Cancer 130(9): 2096-2102.

NO

 

 

 

46.    Hol, L., et al. (2010). "Screening for colorectal cancer: randomised trial comparing guaiac-based and immunochemical faecal occult blood testing and flexible sigmoidoscopy." Gut 59(1): 62-68.

 

 

 

 

47.    Hol, L., et al. (2009). "Screening for colorectal cancer: random comparison of guaiac and immunochemical faecal occult blood testing at different cut-off levels." Br J Cancer 100(7): 1103-1110.

 

 

NO

 

48.    Honda, K. (2004). "A model of perceived risk for colorectal cancer among Japanese Americans." J Cancer Educ 19(4): 251-257.

 

NO

 

 

49.    Hou, W. K. (2010). "Intrapersonal and interpersonal dimensions of cancer perception: a confirmatory factor analysis of the cancer experience and efficacy scale (CEES)." Support Care Cancer 18(5): 561-571.

 

NO

 

 

50.    Hughes, K., et al. (2005). "Guaiac versus immunochemical tests: faecal occult blood test screening for colorectal cancer in a rural community." Aust N Z J Public Health 29(4): 358-364.

 

 

 

 

51.    Kapidzic, A., et al. (2012). "Quality of life in participants of a CRC screening program." Br J Cancer 107(8): 1295-1301.

 

NO

 

 

52.    Kemeny, M. M. (2004). "Surgery in older patients." Semin Oncol 31(2): 175-184.

 

NO

 

 

53.    Kempe, K. L., et al. (2012). "Automated phone and mail population outreach to promote colorectal cancer screening." Am J Manag Care 18(7): 370-378.

 

 

NO

 

54.    Khalid-de Bakker, C., et al. (2011). "Participation in colorectal cancer screening trials after first-time invitation:  a systematic review." Endoscopy 43(12): 1059-1086.

 

NO

 

 

55.    Klaver, Y. L., et al. (2012). "Outcomes of elderly patients undergoing cytoreductive surgery and perioperative intraperitoneal chemotherapy for colorectal cancer peritoneal carcinomatosis." J Surg Oncol 105(2): 113-118.

NO

 

 

 

56.    Kluhsman, B. C., et al. (2012). "A pilot study for using fecal immunochemical testing to increase colorectal cancer screening in Appalachia, 2008-2009." Prev Chronic Dis 9: E77.

 

NO

 

 

57.    Ko, C. W., et al. (2003). "Fecal occult blood testing in a general medical clinic: comparison between guaiac-based and immunochemical-based tests." Am J Med 115(2): 111-114.

NO

 

 

 

58.    Labianca, R. and B. Merelli (2010). "Screening and diagnosis for colorectal cancer: present and future." Tumori 96(6): 889-901.

 

 

 

NO

59.    Ladabaum, U., et al. (2011). "Screening for colorectal cancer with a blood test: Projected effectiveness and cost-effectiveness of a novel plasma methylated septin-9 DNA (mSEPT9) assay." Gastroenterology 140(5): S50-S51.

 

 

 

NO

60.    Laiyemo, A., et al. (2012). "DC screen for life program: Taking colon cancer screening to the uninsured." Am. J. Gastroenterol. 107: S569-S570.

 

 

NO

 

61.    Lam, T. Y. T., et al. (2011). "Three-year follow up on a colorectal cancer screening program in Hong Kong: A prospective cohort study." J. Gastroenterol. Hepatol. 26: 6-7.

 

NO

 

 

62.    Lane, J. M., et al. (2010). "Can quantitative immunochemical fecal occult blood tests be used in single sample format without compromising colorectal neoplasia yield?" Gastroenterology 138(5): S184.

 

 

NO

 

63.    Launoy, G. (2009). "[Improvement in screening for colorectal cancer associated with the use of immunochemical faecal occult blood test]." Pathol Biol (Paris) 57(6): 488-492.

 

 

 

NO

64.    Lee, V., et al. (2006). "Meaning-making and psychological adjustment to cancer: development of an intervention and pilot results." Oncol Nurs Forum 33(2): 291-302.

 

NO

 

 

65.    Levi, Z., et al. (2011). "A higher detection rate for colorectal cancer and advanced adenomatous polyp for  screening with immunochemical fecal occult blood test than guaiac fecal occult blood test, despite lower compliance rate. A prospective, controlled, feasibility study." Int J Cancer 128(10): 2415-244.

 

 

 

 

66.    Levy, B. T., et al. (2012). "Mailed fecal immunochemical tests plus educational materials to improve colon cancer screening rates in Iowa Research Network (IRENE) practices." J Am Board Fam Med 25(1): 73-82.

 

 

NO

 

67.    Li, C. M., et al. (2007). "Factors associated with referral compliance of abnormal immunochemical faecal occult blood test." J Med Screen 14(4): 186-190.

NO

 

 

 

68.    Manne, S., et al. (2003). "Understanding intention to undergo colonoscopy among intermediate-risk siblings of colorectal cancer patients: a test of a mediational model." Prev Med 36(1): 71-84.

 

NO

 

 

69.    Mantyh, C. R., et al. (2001). "Coloplasty in low colorectal anastomosis: manometric and functional comparison with straight and colonic J-pouch anastomosis." Dis Colon Rectum 44(1): 37-42.

 

NO

 

 

70.    Masya, L. M., et al. (2009). "Preferences for outcomes of treatment for rectal cancer: patient and clinician utilities and their application in an interactive computer-based decision aid." Dis Colon Rectum 52(12): 1994-2002.

 

NO

 

 

71.    McQueen, A., et al. (2008). "Construct validity and invariance of four factors associated with colorectal cancer screening across gender, race, and prior screening." Cancer Epidemiol Biomarkers Prev 17(9): 2231-2237.

 

NO

 

 

72.    Nadel, M. R., et al. (2010). "Fecal occult blood testing beliefs and practices of U.S. primary care physicians: serious deviations from evidence-based recommendations." J Gen Intern Med 25(8): 833-839.

 

 

NO

 

73.    Osborne, J. M., et al. (2012). "Patterns of participation over multiple rounds of faecal immunochemical test-based screening for colorectal cancer." J. Gastroenterol. Hepatol. 27: 27.

 

NO

NO

 

74.    Park, D. I., et al. (2010). "Comparison of guaiac-based and quantitative immunochemical fecal occult blood testing in a population at average risk undergoing colorectal cancer screening." Am J Gastroenterol 105(9): 2017-2025.

NO

 

 

 

75.    Park, M. J., et al. (2011). "Trends in the National Cancer Screening Program for colorectal cancer in the Republic of Korea, 2004-2009." Asian Pac J Cancer Prev 12(12): 3489-3493.

 

NO

 

 

76.    Potter, M. B., et al. (2010). "Comparative effectiveness of two pharmacy-based colorectal cancer screening interventions during an annual influenza vaccination campaign." J Am Pharm Assoc (2003) 50(2): 181-187.

NO

 

 

 

77.    Quintero, E., et al. (2012). "Colonoscopy versus fecal immunochemical testing in colorectal-cancer screening." N Engl J Med 366(8): 697-706.

 

NO

 

 

78.    Rabeneck, L., et al. (2012). "Fecal immunochemical tests compared with guaiac fecal occult blood tests for population-based colorectal cancer screening." Can J Gastroenterol 26(3): 131-147.

 

 

 

 

79.    Rao, R. S., et al. (2004). "Understanding the factors underlying disparities in cancer screening rates using  the Peters-Belson approach: results from the 1998 National Health Interview Survey." Med Care 42(8): 789-800.

 

 

NO

 

80.    Ritvo, P., et al. (2008). "Factorial validity and invariance of a survey measuring psychosocial correlates of colorectal cancer screening in Ontario, Canada--a replication study." Cancer Epidemiol Biomarkers Prev 17(11): 3279-3283.

 

NO

 

 

81.    Roslani, A. C., et al. (2012). "Screening for colorectal neoplasias with fecal occult blood tests: false-positive impact of non-dietary restriction." Asian Pac J Cancer Prev 13(1): 237-241.

 

 

NO

 

82.    Rozen, P. et al. (2000). "Comparative screening with a sensitive guaiac and specific immunochemical occult  blood test in an endoscopic study." Cancer 89(1): 46-52.

 

NO

 

 

83.    Rustagi, T. and V. R. Konjeti (2012). "Survey of primary care residents to assess awareness of updated 2008 ACG guidelines for colorectal cancer screening." Am. J. Gastroenterol. 107: S809.

 

 

 

NO

84.    Sastre, J., et al. (2011). "First-line single-agent cetuximab in elderly patients with metastatic colorectal  cancer. A phase II clinical and molecular study of the Spanish group for digestive tumor therapy (TTD)." Crit Rev Oncol Hematol 77(1): 78-84.

 

NO

 

 

85.    Schiff, L., et al. (2009). "Development of serum tests for colorectal cancer screening." Value Health 12(7): A257.

 

 

NO

 

86.    Segnan, N., et al. (2007). "Comparing attendance and detection rate of colonoscopy with sigmoidoscopy and FIT for colorectal cancer screening." Gastroenterology 132(7): 2304-2312.

 

NO

 

 

87.    Senore, C., et al. (2010). "The added value of immunochemical FOBT following a negative screening sigmoidoscopy." Gastroenterology 138(5): S186-S187.

NO

 

 

 

88.    Senore, C., et al. (2012). "Offering people a choice for colorectal cancer screening." Gut.

NO

 

 

 

89.    Senore, C., et al. (2011). "Acceptability and side-effects of colonoscopy and sigmoidoscopy in a screening setting." J Med Screen 18(3): 128-134.

 

NO

 

 

90.    Senore, C., et al. (2009). "Comparing diagnostic yield and interval cancer rates of different strategies of colorectal cancer screening." Gastroenterology 136(5): A53.

 

 

NO

 

91.    Sharaf, R. N. and U. Ladabaum (2013). "Comparative effectiveness and cost-effectiveness of screening colonoscopy vs. sigmoidoscopy and alternative strategies." Am J Gastroenterol 108(1): 120-132.

 

 

NO

 

92.    Shuhaibar, M., et al. (2011). "A comparative study of faecal occult blood kits in a colorectal cancer screening  program in a cohort of healthy construction workers." Ir J Med Sci 180(1): 103-108.

NO

 

 

 

93.    Simonds, V. W., et al. (2011). "Cancer screening among Native Americans in California." Ethn Dis 21(2): 202-209.

 

NO

 

 

94.    SR, C., et al. "An advance notification letter increases participation in colorectal cancer screening." Journal of medical screening.

 

NO

 

 

95.    SR, C., et al. "A randomised trial of the impact of new faecal haemoglobin test technologies on population participation in screening for colorectal cancer." Journal of medical screening.

 

 

 

 

96.    Stare, J., et al. (2005). "Goodness of fit of relative survival models." Stat Med 24(24): 3911-3925.

 

NO

 

 

97.    Stegeman, I., et al. (2012). "Implementation of population screening for colorectal cancer by repeated Fecal Immunochemical Test (FIT): Third round." BMC Gastroenterol. 12.

NO

 

 

 

98.    Sule, A. Z., et al. (2007). "One stage procedure in the management of acute sigmoid volvulus without colonic lavage." Surgeon 5(5): 268-270.

 

NO

 

 

99.    Sung, J. J., et al. (2011). "Three years follow-up on a colorectal cancer screening program: A prospective cohort of 4,961 asymptomatic subjects." Gastroenterology 140(5): S182-S183.

 

NO

 

 

100. Svensson, E., et al. (2006). "Frailty modelling of colorectal cancer incidence in Norway: indications that individual heterogeneity in risk is related to birth cohort." Eur J Epidemiol 21(8): 587-593.

 

NO

 

 

101.Tan, W. S., et al. (2012). "Opportunistic screening for colorectal neoplasia in singapore using an immunochemical faecal occult blood test (FIT) by the Singapore Cancer Society." Colorectal Dis. 14: 3.

 

NO

 

 

102.Terhaar sive Droste, J. S., et al. (2011). "Higher fecal immunochemical test cutoff levels: lower positivity rates but still  acceptable detection rates for early-stage colorectal cancers." Cancer Epidemiol Biomarkers Prev 20(2): 272-280.

 

 

NO

 

103.Tiro, J. A., et al. (2005). "Factorial validity and invariance of a survey measuring psychosocial correlates of colorectal cancer screening among African Americans and Caucasians." Cancer Epidemiol Biomarkers Prev 14(12): 2855-2861.

 

NO

 

 

104.Van Dam, L., et al. (2010). "Comparing participants and non-participants of a randomized colorectal cancer screening program using guaiac-based and immunochemical fecal occult blood test and flexible sigmoidoscopy." Gastroenterology 138(5): S191.

 

NO

 

 

105.Van Dam, L., et al. (2010). "Experiences of general practitioners regarding their role in the referral process for colonoscopy after a positive colorectal cancer screening test." Gastroenterology 138(5): S191.

NO

 

 

 

106.VanDam, L., et al. (2010). "Comparison of participants and non-participants in a flexible sigmoidoscopy screening program, with an alternative invitation for fecal immunochemical testing." Gastroenterology 138(5): S351.

 

NO

 

 

107.Van Roon, A. H., et al. (2011). "Attendance and diagnostic yield of repeated fecal immunochemical test screening with intervals of 1, 2, or 3 years: A comparative population-based colorectal cancer screening trial." Gastroenterology 140(5): S405.

 

NO

 

 

108.Van Roon, A. H., et al. (2010). "Fecal immunochemical test (FIT) characteristics by sample return time in a population-based colorectal cancer screening trial." Gastroenterology 138(5): S133.

 

 

NO

 

109.Van Roon, A. H., et al. (2010). "Attendance and diagnostic yield of one versus two-sample fecal immunochemical test (FIT) screening; a comparative population-based colorectal cancer trial." Gastroenterology 138(5): S134.

 

 

NO

 

110.Van Roon, A. H. C., et al. (2013). "Random comparison of repeated faecal immunochemical testing at different intervals for population-based colorectal cancer screening." Gut 62(3): 409-415.

 

 

NO

 

111.Van Roosbroeck, S., et al. (2012). "Population-based screening for colorectal cancer using an immunochemical faecal occult blood test: a comparison of two invitation strategies." Cancer Epidemiol 36(5): e317-324.

 

NO

 

 

112. Van Rossum, L. G., et al. (2009). "Cutoff value determines the performance of a semi-quantitative immunochemical faecal occult blood test in a colorectal cancer screening programme." Br J Cancer 101(8): 1274-1281.

 

 

NO

 

113. Van Rossum, L. G., et al. (2008). "Random comparison of guaiac and immunochemical fecal occult blood tests for colorectal cancer in a screening population." Gastroenterology 135(1): 82-90.

 

 

 NO

 

114. Van Turenhout, S. T., et al. (2012). "Anticipating implementation of colorectal cancer screening in The Netherlands: a  nation wide survey on endoscopic supply and demand." BMC Cancer 12: 46.

 

 

NO

 

115. Vanness, D. J., et al. (2011). "Comparative economic evaluation of data from the ACRIN National CT Colonography Trial with three cancer intervention and surveillance modeling network microsimulations." Radiology 261(2): 487-498.

 

NO

 

 

116. Vart, G., et al. (2012). "Comparing participation rates between immunochemical and guaiac faecal occult blood tests: a systematic review and meta-analysis." Prev Med 55(2): 87-92.

 

 

 

 

117.Watts, B. G., et al. (2003). "Intention to be screened over time for colorectal cancer in male automotive workers." Cancer Epidemiol Biomarkers Prev 12(4): 339-349.

NO

 

 

 

118.Weiss, J. M. and P. R. Pfau (2012). "New era for stool screening tests: Fecal immunochemical tests, DNA, and beyond." Curr. Colorectal Cancer Rep. 8(1): 1-5.

 

 

 

NO

119.Williams, J. A., et al. (1987). "Evaluation of an immunochemical test for faecal occult blood in screening for colorectal neoplasia in a high risk group." Aust N Z J Surg 57(12): 951-957.

NO

 

 

 

120.Wilschut, J., et al. (2010). "Quantitative immunochemical fecal occult blood screening under a colonoscopy constraint: A Higher cut-off level, a smaller age range or a longer screening interval? A cost-effectiveness analysis." Gastroenterology 138(5): S183.

 

 

NO

 

121.Wilschut, J., et al. (2010). "Should we offer individuals two samples of a fecal immunochemical test for colorectal cancer screening instead of one? A cost-effectiveness analyis." Gastroenterology 138(5): S183-S184.

 

 

NO

 

122.Wong, C. K., et al. (2011). "Efficacy of a single day fecal immunochemical occult blood testing (FIT) collection strategy for screening relevant colorectal neoplasias." Gastroenterology 140(5): S410.

 

 

NO

 

123.Wong, C. K. W., et al. (2012). "The sensitivity and specificity of guaiac and immunochemical fecal occult blood tests for the detection of advanced colonic adenomas and cancer." Int. J. Colorectal Dis. 27(12): 1657-1664.

 

 

NO

 

124. Wong, M. C., et al. (2012). "Changes in the choice of colorectal cancer screening tests in primary care settings from 7,845 prospectively collected surveys." Cancer Causes Control 23(9): 1541-1548.

 

NO

 

 

126. Wong, M. C. S., et al. (2010). "A comparison of the acceptance of immunochemical faecal occult blood test and colonoscopy in colorectal cancer screening: A prospective study among Chinese." Aliment. Pharmacol. Ther. 32(1): 74-82.

 

NO

 

 

127.Young, C. W., et al. (1988). "Phase I trial and clinical pharmacological evaluation of hexamethylene bisacetamide administration by ten-day continuous intravenous infusion at twenty-eight-day intervals." Cancer Res 48(24 Pt 1): 7304-7309.

 

NO

 

 

128.Young, G. P. (2009). "Population-based screening for colorectal cancer: Australian research and implementation." J Gastroenterol Hepatol 24 Suppl 3: S33-42.

 

 

 

NO

129.Young, G. P. (2012). "New Developments in Screening for Colorectal Cancer: Report on the World Endoscopy Organization Workshop Chicago, May 2011." Pract. Gastroenterol. 36(12): 32-36.

 

 

 

NO

130.Young, G. P. and S. Cole (2007). "New stool screening tests for colorectal cancer." Digestion 76(1): 26-33.

 

 

 

NO

131.Young, G. P. and S. R. Cole (2009). "Which fecal occult blood test is best to screen for colorectal cancer?" Nat. Clin. Pract. Gastroenterol. Hepatol. 6(3): 140-141.

 

 

 

NO

132.Young, G. P., et al. (2003). "Prescreening evaluation of a brush-based faecal immunochemical test for haemoglobin." J Med Screen 10(3): 123-128.

 

NO

 

 

133.Zajac, I. T., et al. (2010). "Endorsement by the primary care practitioner consistently improves participation  in screening for colorectal cancer: a longitudinal analysis." J Med Screen 17(1): 19-24.

 

NO

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

APPENDIX 3

 

 

 

published

2011

2003

2005

2012

2008

2010

2010

2005

2010

2012

period study conducted

unclear

April-August 2001

June 2002

studies from 1999-2012

not found

November 2006 to May 2008

between November 2006 and November 2007

The initial mail-out was conducted in November 2000.

2008

2000-2011

country(ies) of study

Israel

Australia

Italy, Lazio region

Italy

USA

NL

NL

Australien, Queensland

Israel

Australia, Italy, Netherlands, USA, Israel

n of studies included (systematic review)

primary study

primary study

primary study

14 in the meta-analysis, 7 double with our search results (Segnan, Ferderici, van Rossum 2008, Hoffmann, Hol 2010 (RCT comparing…), Levi, Quintero 2012

primary study

primary study

primary study

primary study

primary study

7 (6 are also included in our search)

sponsoring

Eiken Japan provided the OC-MICROTM instrument, reagents and partial financial support for administration.

Hemoccult SENSA and FlexSure OBT cards were purchased from Beckman Coulter Inc. (Palo Alto CA, USA). Enterix Inc. (Portland ME, USA) provided InSure test kits. Grants from Bushell Foundation and Enterix Inc. provided part support for salaries (SC, BC).

n.a.

partially funded by the Italy Ministry of Health, through a project coordinated by the Agenzia Nazionale per i Servizi Sanitari and conducted by Laziosanità: ‘Strumenti e metodi per il governo dei processi di innovazione tecnologica, clinica ed organizzativa nel SSN – Un sistema integrato di ricerca’,  sub-project ‘Analysis of the impact of professional involvement in evidence generation for the HTA process’ grant no. I85J07000080001.

unclear

This trial was funded by the Dutch Cancer Society (EMCR 2006-3673), and the Dutch Ministry of Health, Health Care Prevention Program–Implementation (ZonMw 2006-5877).

This trial was funded by the Dutch Cancer Society (EMCR 2006-3673), the Dutch Ministry of Health, Health Care Prevention Program–Implementation (ZonMw 2006-5877), Olympus Medical Systems Europe GmbH, Hamburg, Germany and Eiken Chemical Co., Tokyo, Japan.

This research was funded by Queensland Health. In addition, funding was subsidised by Enterix (Inc), which made the !nform FOBT kit and its analysis available at a highly discounted rate, and the pathology laboratory at Townsville General Hospital, which provided analysis of Hemoccult-II kits at a greatly reduced fee.

Eiken Japan provided the OC-MICROTM instrument, reagents and partial financial support for administration.

This research was funded via studentship provided by The Guildford Tumour Screening (G.U.T.S) charity for part fulfilment of the degree PhD Health Psychology at the University of Surrey

Quantitative-Experimental

Quantitative-Experimental/ RCT

Quantitative-Experimental/ RCT

Quantitative-Experimental/ RCT

meta-analysis

Quantitative- Observational

Quantitative-Experimental/ RCT

Quantitative-Experimental/ RCT

Quantitative-Experimental/ RCT

Quantitative-Experimental/ RCT

systematic review

Trial registration number (for RCTs only)

n.a.

n.a.

n.a.

n.a.

n.a.

n.a.

n.a.

n.a.

n.a.

n.a.

Methods

target population and the primary area clinics were clustered according to socioeconomic status (SES). into three SES classes (high, medium, low) using software based on postal code and estimated income. Clinics were then randomly allocated into either the FIT or gFOBT arm.

randomly selected from the electoral roll of the Australian Electoral Commission

 13 selected hospitals to accurately represent gastroenterology units and geographic areas. All GPs (more than 100 patients in the target population (age 50–74) included in the survey

Relevant publications were identified by MEDLINE/EMBASE and other databases for the period 1999–2012. A previous systematic review was used for the period before 1966–1999. RCTs and controlled studies including a direct comparison of the uptake rates among different options for CRC screening were included.

Purposive sampling from waiting areas of 3 community health centres. Patients aged 50-80 recruited. They were asked to rate 8 hypothetical CRC screening tests scenarios

A representative sample of the Dutch population (aged 50–74 years) was randomised to be invited for gFOBT, FIT and FS screening. participants were asked to complete a questionnaire in the waiting area of the endoscopy unit

From a representative sample of the Dutch population aged 50–74 years, a random sample of 15 011 individuals was taken by computer generated algorithm and 1:1:1 randomised

The two groups were randomly allocated to kit type by flipping a coin. Patients from the largest and smallest practices received the immunochemical kit, and patients from the other two practices received the guaiac test..

Nine medium-sized primary care clinics (1,000–2,000 patients) were included, three clinics from each SES.

search in Pubmed and Cochrane Db, includion of RCTs comparing FIT versus gFOBT, exclusion of studies comparing with invasive methods,

Outcomes measured

Primary outcomes 1) To compare the ‘kit compliance’ 2) To compare the compliance for ‘kit return’ 3) To compare the overall compliance for test uptake

Secondary outcome

1) to assess the effect of the sociodemographic factors on the compliance for test uptake.

Primary outcomes

1) Participation rate Secondary outcome

1) demographic variables' impact on participation

Primary outcomes

1) percentage of compliance

Primary outcomes

1) Adherence

2) detection rates for advanced neoplasia and cancer

Primary outcomes

1) screening preferences 2) variation in crc among racially ethnically diverse primary care patients

Primary outcomes

1) To assess differences in perceived burden and willingness to return for a second screening round among participants

Primary outcomes

1) participation rate to each of the three screening strategies

Primary outcomes

1) screening participation in a rural community, comparing guaiac and immunochemical tests

Primary outcomes

1) to compare FIT with G-FOBT in screening 2) to assess the feasibility of this approach in the urban population in Israel, with special relation to different socioeconomic classes

Primary outcomes

1) to compare participation rates of gFOBT and FIT

Secondary outome

2 to assess which characteristics of the test acted as barriers or facilitators to participation

participants

Eligible participants aged 50–74 years were linked to the nine selected primary care clinics. Patients who had an established CRC or inflammatory bowel disease were excluded.

A pool of 4000 potential invitees

CRC screening target population (i.e. people aged 50–74) is 1.5 million

Population sample

75 participants per racial/ethnic group

In total 402/481 (84%) gFOBT and 530/659 (80%) FIT screenees returned their questionnaire

Population sample

A rural Queensland community was selected, with a population of approximately 15,000 people (approximately 4,200 were aged 50 years or older)

A total of 12,539 patients were included in the study: 4,657 patients of Group A had FIT and 7,880 patients of Group B had G-FOBT.

The cohorts invited ranged from 1818 (Cole 2003) to 20623 (van Rossum 2008).

n of participants

16132 [10668 (gFOBT) + 5464 (FIT)]

1818 (3 groups of each 606)

n =7320

197910; Five studies compared g-FOBT with FIT, including 59 729 randomised subjects

220

852

15011

3358; Of the 3,861 individuals contacted by the study, 503 (13.0%) received both immunochemical and guaiac kits.

12,539 (4,657 FIT; 7,880 G-FOBT)

the cohorts invited ranged from 1818 (Cole 2003) to 20623 (van Rossum 2008).

age range

60-74

50-69

50-74

50-74 (4x), 50-75 (4x); 55-64 (3x); 50-54/65-69 (1x); 50-80 (1x); 50-69 (1x)

50-80 (mean 59)

50–74

50-74

50-74

mean age FIT: 60.4, mean age FOBT 61.3

50+

gender proportion m to f

43,1% male; 56,9% female

49,5% male, 50,5% female (own calculation of table 1)

Guaiac 46.9% men  FIT 45.8% men

male 49.5%; female 50.5% (own calculation of all studies included in the meta analysis)

not specified. Analysis was controlled by age and gender for all groups

45.3% male (FOBT), 50.6% male (FIT), 50.7% (FS)

participation OR for Women 1.1 (0.9 to 1.4) (FOBT)  1.3 (1.1 to 1.4)(FIT) 0.9 (0.8 to 1.0)(FS)

51.2% female

45.4% male for FIT, 42.6% male for FOBT

n.a.

health status

screening population

screening population

screening population

screening population

screening population

screening population

screening population

screening population

screening population

screening population

ethnic minority

10,8% immigrants

Exposure of this population to screening was low by US standards and prior participation in screening had been less than 20%.

no

n.a.

74 white, 60 Africans, 78 Hispanic

5% non Cuacasian

n.a.

no

n.a.

n.a.

specific population group (i.e. economic situation, uninsured, speicif workers,…)

34% high SES, 36,6% medium SES, 29,4% low SES

 

no

n.a.

racically and ethnically diverse

no

n.a.

no

SES controlled

n.a.

Setting (e.g. population screening program – rounds - opportunistic screening etc.)

primary care clinic registrees, setting population-based like

Typical urban setting that is relatively naïve to the value and practice of screening

population screening

population screening

population screening

population screening

population screening

population screening

population screening

population based program setting

intervention

FIT

FIT

FIT

FIT/gFOBT/endoscopy

all possible screening tests

FIT

FIT

FIT

FIT

FIT

comparator

gFOBT

gFOBT

gFOBT

FIT/gFOBT/endoscopy

using white people as referrence for the regression model

FOBT, FS

FOBT, FS

FOBT, FS

FOBT

gFOBT

 
 

 

 

APPENDIX 4 Quality Assessment of selected primary studies QUORUM – 2
 
 

 

 

 

 

 

 

5.       Birkenfeld, S., et al. (2011).

17.    Cole, S. R., et al. (2003).

30.    Federici, A., et al. (2005).

40.    Hawley, S. T., et al. (2008).

44.    Hol, L., et al. (2010).

46.    Hol, L., et al. (2010). 59(1): 62-68.

50.    Hughes, K., et al. (2005).

65.    Levi, Z., et al. (2011).

116. Vart, G., et al. (2012).

 

Internal validity

Select: + , - , ? or NR “Not relevant or of minor relevance in this study”

 

 

 

 

 

 

 

 

 

Add free text to explain

 

 

 

 

 

 

 

 

 

Selection

Was the sequence generation adequate?

+ - ? NR

+

+

+

NR

?

+

+

+

75%+

Was allocation concealment adequate?

+ - ? NR

NR

NR

NR

NR

NR

+

+

+

60%+

Was a consecutive or random sample of patients enrolled? (applies to non randomized studies)

+ - ? NR

NR

NR

NR

+

 

 

 

 

 

Did the study avoid inappropriate exclusions?

+ - ? NR

+

+

+

+

NR

+

+

+

nr

Were the baseline characteristics similar? (applies to non randomized studies)

+ - ? NR

+

+

+

+

+

+

+

+

nr

Could the selection of patients have introduced bias?

YES  NO

NO

NO

no

no

NO

NO

NO

+

75%-

Conduct

Were participants and personnel blinded?

+ - ? NR

-

-

-

-

NR

+

-

nr

nr

Were the  co-interventions identical?

+ - ? NR

+

-

-

NR

+

+

+

+

nr

Was the number of withdrawals or uncompleted measurements appropriately low?

+ - ? NR

+

+

+

+

+

+

+

+

nr

Could the conduct of the intervention have introduced bias?

YES  NO

NO

YES

no

NR

no

no

yes (by the information given to the test)

yes (by the information given to the test)

nr

Interpretation

Were outcome assessors  blinded?

+ - ? NR

-

-

-

NR

NR

+

+

nr

nr

Could the interpretation of the intervention have introduced bias?

YES  NO

NO

NO

NO

NR

NO

no

no

no

nr

Analysis and reporting

Was data analyzed appropriately?

+ - ? NR

+

+

+

+

+

+

+

+

nr

Was incomplete outcome data addressed?

+ - ? NR

+

+

+

+

+

+

+

+

nr

Was the study free from selective reporting?

+ - ? NR

?

+

+

+

+

+

+

+

nr

Other

Was the study funding independent from  manufacturer?

+ - ? NR

-

-

+

+

+

-

?

-

nr

Free of other bias? Which?

+ - ? NR

 

+

+

+

+

+

+

+

nr

 

 

 

 

 

 

 

 

 

 

 

 

 

External validity

 

 

 

 

 

 

 

 

 

 

 

Relevant patient group

+ - ?

+

+

+

+

+

+

+

+

+

 

Relevant intervention

+ - ?

+

+

+

+

+

+

+

+

+

 

Relevant comparator

+ - ?

+

+

+

+

+

+

+

+

+

 

Relevant endpoint measures

+ - ?

+

+

+

+

+

+

+

+

+

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

APPENDIX 5

 

Quality Assessment of selected systematic reviews  AMSTAR (http://amstar.ca/Amstar_Checklist.php)

 

 

 

 

 

Hassan et al., 2012

 

Vart et al. 2012

 

For each question, select:

 

  • Yes
  • No
  • Can’t  answer
  • Not applicable

 

  1. Was the sequence generation adequate?

 NA

NA

  1. Was there duplicate study selection and data extraction?

Yes

Yes

  1. Was a comprehensive literature search performed?

Yes

Yes

  1. Was the status of the publication used as an inclusion criterion?

Yes

No

  1. Was a list of studies (included and excluded) provided?

Yes (in the on line version of the article)

No

  1. Were the characteristics of the included studies provided?

 

 

Yes

Yes

  1. Was the scientific quality of the included studies assessed and documented?

 

Yes

Yes

  1. Was the scientific quality of the included studies assessed used appropriately in formulating conclusions?

Yes

No

  1. Were the methods used to combine the findings of studies appropriate?

Yes

Yes

  1. Was the likelihood of publication bias assessed?

No

No

  1. Was the conflict of interest included?

Yes

Yes

 

9/11 (minimum 6 score)

6/11 (minimum 6 score)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Authors: Ingrid Wilbacher

Summary

 

Rights

Duties/responsibilities

Patient

Sufficient information and informed consent {86, 87, 92}

Participation/compliance

 

right of access to (best) health care {12,13,14}

Risk reduction

 

"freedom in participation" {16, 87}

Allow data use for adequate follow up and fluent follow up in case of positive test result

 

Data protection {21}

Pay tax or health insurance contributions

 

Access without discrimination {25-31,71}

 
 

Good quality care (state of the art) {12,13,14}

 
 

Search for healthcare abroad in case of unequalities due to regionalism {32}

 
   

Provider

Right to "physical harm" in case of treatment and with the implicit understanding and consent of the patient. {15}

Information {92}

 

Right to charge

Data protection/ adequate use {21,22}

  

Provide state of the art quality

   

Payer

Decision of the contents (oft he screening program) based on HTA {32, 77}

responsibility of providing public health issues and the organization of the delivery {64,65,81}

 

Collect contributions (like social insurance or tax)

Provide quality at least according to appropriate market authorization (procurement)

  

Contract providers (national law)

  

provide follow up treatment in case of positive result (at least abroad; {76}

   

Others

Industry: healthcare marketing takes place and provides an own journal{91}

Industry: quality of the test;  market authorisation

 

EU: consumer protection issues

EU: Provide transparent market authorization processes

  

Reduced advertisement in health care {national status){88,89,90}

  

Appropriate protection of minors and incompetent persons {71,72,73}

 

Introduction

The legal aspects focus on the legal basics for crc screening, special requirements and specific groups in legislation.

Methodology

Frame

A modified collection scope is used in this domain.

TechnologyFecal Immunochemical Test (FIT) for colorectal cancer screening
Description

FITs use an antibody (immunoglobulin) specific to human globin, the protein component of haemoglobin, to detect fecal occult blood. Immunochemical tests have improved test characteristics compared to conventional guaiac-based tests for fecal occult blood. FIT should not be subject to interference from dietary blood and it is more specific to bleeding from the distal gastrointestinal tract. They could be analytically and clinically more sensitive and specific, Their measurement can be automated and the user can adjust the concentration at which a positive result is reported. A wide range of qualitative and quantitative tests is presently available, with varying levels of sensitivity and specificity (like Hem-SP/MagStream H, Fujirebio Inc. Japan ; OC-Sensor, Eiken Chemical Co., Tokyo, Japan;    FOB Gold, Medinostics Products Supplier; Sentinel Diagnostics SpA, Milan, Italy).

Intended use of the technologyScreening

CRC screening with faecal inmunochemical test (FIT) for detection of occult blood in the stool associated with colorectal lesions (adenomas and CRC).

The use of the test is considered under conditions of population based colorectal cancer screening, in the context of organised cancer screening programmes as recommended by the EU. Early detection and treatment of colorectal lesions before they become symptomatic has the potential to improve control of the disease, reducing morbidity and mortality associated to CRC. Early treatment of invasive lesions can be generally less detrimental for quality of life. The endoscopic removal of pre-malignant lesions also reduces the incidence of CRC by stopping the progression to cancer. Colorectal cancers and adenomatous polyps bleed has providing fecal blood haemoglobin as the biomarker of choice for current screening programmes. Stool samples could be periodically taken and analyzed for the presence of occult blood, as an early sign of colorectal lesions (adenoma or CRC).

Target condition
Adenomas, as non-malignant precursor lesions of ColoRectal Cancer (CRC).
Target condition description

CRC is the third most common in incidence and the fourth most common cause of cancer death worldwide. CRC is particularly suitable for screening. The disease is believed to develop in a vast majority of cases from non-malignant precursor lesions called adenomas. Adenomas can occur anywhere in the colorectum after a series of mutations that cause neoplasia of the epithelium. At some time , the adenoma may invade the submucosa and become malignant. Initially, this malignant cancer is not diagnosed and does not give symptoms  (preclinical phase). It can progress from localised (stage I) to metastasised (stage IV) cancer, until it causes symptoms and is diagnosed. Only 5–6% of the population actually develop CRC. The average duration of the development of an adenoma to CRC is estimated to be  at least 10 years. This long latent phase provides a window of opportunity for early detection of the disease.

Target population

Target population sex: Any. Target population age: adults and elderly. Target population group: Healthy and/or asymptomatic people.

Target population description

Adults, average risk of CRC, aged 50 years or over.

The best age range for offering gFOBT or FIT screening has not been investigated in trials. Circumstantial evidence suggests that mortality reduction from gFOBT is similar in different age ranges between 45 and 80 years .The age range for a national screening programme should at least include people aged 60 to 64 years in which CRC incidence and mortality are high and life-expectancy is still considerable. Only the FOBT for men and women aged 50–74 years has been recommended todate by the EU (Council Recommendation and the European guidelines for quality assurance in CRC screening and diagnosis).

Members of families with hereditary syndromes, previous diagnosis of CRC or pre-malignant lesions should follow specific surveillance protocols and are not included in the target population

ComparisonCRC screening with Guaiac –based fecal occult blood test (gFOBT)
Description

CRC screening with Guaiac–based fecal occult blood test (gFOBT)

The guaiac-based FOBT is still a commonly used method for detecting blood in faeces. To detect hemoglobin the test uses guaiac gum and its efficacy as a colorectal cancer screening test has been analyzed in several randomised controlled trials. The test detects the haem component of haemoglobin, which is identical across human and animal species and is chemically robust and only partially degraded during its passage through the gastrointestinal tract. gFOBTs cannot distinguish between human blood and blood residues from the diet.

Many guaiac-based tests are currently on the market (like Coloscreen, Helena Laboratories,Texas,USA; Hema-screen Immunostics Inc.; Hemoccult, Beckman Coulter Inc.; Hemoccult SENSA, Beckman Coulter Inc.; MonoHaem, Chemicon Europe Ltd; Hema-Check, Siemens PLC; HemaWipe, Medtek Diagnostics LLC)

The use of the test is considered under conditions of population based colorectal cancer screening, in the context of organised cancer screening programmes as recommended by the EU. Population-based programmes have been rolled out nationwide in several European countries. Many member states  haveestablished nationwide non-population-based programmes. Some states are planning or piloting a nationwide population-based programme. These have  adopted only FOBT, some only FIT, some a mix between FOBT and endoscopy, or only colonoscopy.

Outcomes

CUR and TEC

  • Health problems (target condition)
  • Epidemiology
  • Burden of disease
  • Target population
  • Current management of the condition
  • Features of the technology
  • Life-Cycle
  • Regulatory status
  • Utilization
  • Investments and tools required to use the technology
  • Training and information needed to use the technology

SAF

  • Colonoscopy probability of perforation
  • Colonoscopy with polypectomy probability of perforation
  • Colonoscopy probability of death following perforation
  • Probability of bleeding following colonoscopy
  • Psychological harms from false-negatives and false-positives (and generally from participating in screening program)

EFF

  • Test (FIT and gFOBT) sensitivity for adenomas
  • Test (FIT and gFOBT) sensitivity for cancer
  • Test (FIT and gFOBT) specificity for adenomas
  • Test (FIT and gFOBT) specificity for cancer 
  • Adenoma incidence (detection rates)
  • Rectal cancer incidence (detection rates)
  • Colon cancer incidence (detection rates)
  • CRC incidence (detection rates)
  • Stage distribution of detected cancers
  • Rectal cancer specific mortality
  • CRC specific mortality
  • Overall mortality
  • Life years saved

ECO:

  • Model/template for  national pilots  to assess the costs and benefits of the two alternative  technologies FIT and gFOBT  and also no-programmed-screening
  • Systematic literature search of   available models and/or economic  evaluation for screening colorectal cancer with FIT and gFOBT and no screening programme
  • Resource Utilization: Publicly funded health care payer costs (screening tests, further examinations e.g. labor, colonoscopy  and treatments and administration and organisation costs of screening programme) for FIT and gFOBT (in cooperation with ORG)
  • Cost per Case detected (average, marginal, incremental) =  intermediate outcome – optional, not decided yet (relevant for deciding how often a test should be carried out and what are the incremental costs for a “new” detected case
  • Indirect Costs: not for the Core modell (should be decided later on)
  • Test accuracy: from SAF
  • Cost effectiveness analysis: HRQoL measures (both generic and context specific) (EFF and SAF for help, own Lit.research), ICER

 ORG:

  • Responsiveness of target population to invitation
  • Invitation-reminder system
  • Competence of human resources – health professionals
  • Investments needed (material,equipment)
  • Costs of using both tests (FIT, gFOBT)
  • Timeliness of results and future phases
  • Use of tools for process monitoring (completed check lists)
  • Model for Budget Impact Analysis from perspective of the payer

SOC

  • Compliance with the tests (FIT, gFOBT)
  • Anxiety and any psychological effects of using  one test or another
  • Information, counseling, communication (quality of) for the use of tests
  • Satisfaction  
  • Quality of life
  • Equity of access

LEG

  • Information as baseline for an informed consent
  • Harms or inequities that can be taken to court
More information

If the PICO question is extended to other "modern" tests, especially including genetic analysis, we should ask whether there is a focus on detecting people at special risk rather than detecting crc in people with average risk.

The legal domain will definitely focus on terms of equity by defining average risk groups limited by certain age.

The general legal view for the network-use will focus on transborder healthcare (according to the directive which is to be implemented by 25th Oct 2013[1]. This includes the question whether it is the right of a person to get an (organized) screening or not and if yes, is this covered by the cross border healthcare directive?

[1] Directive 2011/24 of the European Parliament and of the Council on the application of patients' rights in cross-border healthcare. Commission of the E