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 3 October 2022]. Available from: http://corehta.info/ViewCover.aspx?id=206

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

<< Costs and economic evaluationOrganisational aspects >>

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.

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