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.

Prognostic tests for breast cancer recurrence (uPA/PAI-1 [FEMTELLE], MammaPrint, Oncotype DX )

UPA/PAI-1 (FEMTELLE), MammaPrint, Oncotype DX compared to Standard of care in selecting treatment for Breast cancer recurrence in females

(See detailed scope below)

HTA Core Model Application for Diagnostic Technologies (1.1)
Core HTA
Published
Tom Jefferson (age.na.s, Italy), Nicola Vicari (age.na.s, Italy), Heike Raatz (SNHTA, Switzerland)
Sarah Baggaley, NICE (Health problem and current use); Antonio Migliore, Agenas (Description and technical characteristics); Iris Pasternack, THL-FINOHTA (Safety); Mirjana Huic, AAZ (Clinical effectiveness), Isaura Vieira, INFARMED (Costs and economic evaluation); Dario Sacchini, A.Gemelli (Ethical analysis); Jennifer Butt, NICE (Organisational aspects); Marco Marchetti, A.Gemelli (Social and Legal aspects)
Agenzia nationale per i servizi sanitari regionali (age.na.s), Italy
A. Gemelli (Italy), AAZ (Croatia), Agenas (Italy), AHTAPol (Poland), AVALIA-t (Spain), INFARMED (Portugal), IPH-RS (Slovenia), NICE (United Kingdom), Regione Veneto (Italy), SNHTA (Switzerland), THL (Finland), UMIT (Austria)
13.6.2011 14.00.00
31.1.2013 18.05.00
Jefferson T, Vicari N, Raatz H [eds.]. Prognostic tests for breast cancer recurrence (uPA/PAI-1 [FEMTELLE], MammaPrint, Oncotype DX ) [Core HTA], Agenzia nationale per i servizi sanitari regionali (age.na.s), Italy ; 2013. [cited 24 October 2021]. Available from: http://corehta.info/ViewCover.aspx?id=113

Prognostic tests for breast cancer recurrence (uPA/PAI-1 [FEMTELLE], MammaPrint, Oncotype DX )

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Collection appendices

Appendix COL-1 Common literature search strategy

Acknowledgments: Jayne Hickton (Information Specialist, NICE)

Literature search

The systematic literature search was performed for the whole Core HTA (9 Domains), according to the Search strategy described below in Appendix COL-1 1, in October 2011, by the Information specialist from NICE (JH), in the following databases: Ovid MEDLINE(R) <1948 to September Week 4 2011>; Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations <October 07, 2011>; Embase <1980 to 2011 Week 40>; Cochrane Issue 4 of 4, Oct 2011; Cinahl (Accessed 12/10/2011); CRD databases: DARE, NHS EED, HTA (Accessed 13/10/2011). In addition, further clinical trials registries were assessed (13/10/2011), for registered ongoing clinical trials or observational studies: ClincalTrials.gov, ISRCTN, metaRegister of Controlled Trials (mRCT) and International Clinical Trials Registry Platform (ICTRP). Last databases update was on 19 December 2011.

Selection of literature

Relevant references available for screening after duplicates removed were screened and assessed for eligibility by two reviewers from Clinical Effectiveness Domain (MH, NS) independently, according Inclusion/ Exclusion criteria (Appendix COL-1 2), in the second part of October 2011. Different selection results were discussed in order to achieve consensus, a third person was involved in case of uncertainty. There were 4508 references. Three additional references were found through hand-search (total of 4511 references). After the title and abstract screening, 616 references which met Inclusion/ Exclusion criteria (Appendix COL-1 2) were retrieved (marked as Included and Ambiguous, for which whole text was needed for final inclusion) (Figure COL-1 1).

Figure COL-1 1. Selection process for all 9 Domains according the PRISMA flowchart

113.EFF Figure 1

The screening results were saved in the word document, in EndNote and Reference Manager databases, and sent to the investigators of all Domains on 31 10 2011.

All further databases updates, till 19 December 2011, with total of 28 additional references were sent to Primary investigators of all Domains to assess them further for eligibility in their Domains. 

Appendix COL-1 1. Literature Search strategy for all Domains

Database: Ovid MEDLINE(R) <1948 to September Week 4 2011>

Search Strategy:

  1. exp Breast Neoplasms/ or exp Inflammatory Breast Neoplasms/ or exp Carcinoma, Lobular/ or exp Carcinoma, Ductal, Breast/ (190871)
  2. ((breast* or mamma*) adj3 (neoplasm* or tumor* or tumour* or cancer* or carcinoma*)).tw. (187456)
  3. or/1-2 (236372)
  4. oncotype*.tw. (139)
  5. (21-gene* or ("21" adj gene*)).tw. (999)
  6. (mammaprint* or (mamma* adj print*)).tw. (58)
  7. (70-gene* or ("70" adj gene*)).tw. (610)
  8. femtelle*.tw. (0)
  9. exp Plasminogen Activator Inhibitor 1/ or exp Plasminogen Activators/ or exp Urokinase-Type Plasminogen Activator/ or exp Receptors, Urokinase Plasminogen Activator/ (38146)
  10. (urokinase* or (plasminogen* adj3 activator*)).tw. (31468)
  11. (upa* adj3 pai-1*).tw. (639)
  12. exp Enzyme-Linked Immunosorbent Assay/ (111107)
  13. (elisa* or enzyme-linked immunosorbent assay*).tw. (119190)
  14. or/4-13 (214620)
  15. 3 and 14 (3455)
  16. Animals/ not Humans/ (3606824)
  17. 15 not 16 (3223)
  18. limit 17 to english language (3026)

Database: Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations <October 07, 2011>

Search Strategy:

  1. ((breast* or mamma*) adj3 (neoplasm* or tumor* or tumour* or cancer* or carcinoma*)).tw. (7287)
  2. oncotype*.tw. (4)
  3. (21-gene* or ("21" adj gene*)).tw. (31)
  4. (mammaprint* or (mamma* adj print*)).tw. (5)
  5. (70-gene* or ("70" adj gene*)).tw. (35)
  6. femtelle*.tw. (0)
  7. (urokinase* or (plasminogen* adj3 activator*)).tw. (818)
  8. (upa adj3 pai-1).tw. (16)
  9. (elisa* or enzyme-linked immunosorbent assay*).tw. (4722)
  10. or/2-9 (5577)
  11. 1 and 10 (98)
  12. limit 11 to english language (93)

Database: Embase <1980 to 2011 Week 40>

Search Strategy:

  1. exp breast tumor/ or exp breast cancer/ or exp breast carcinoma/ or exp inflammatory breast cancer/ (267013)
  2. ((breast* or mamma*) adj3 (neoplasm* or tumor* or tumour* or cancer* or carcinoma*)).tw. (219643)
  3. or/1-2 (298799)
  4. oncotype.tw. (215)
  5. (21-gene* or ("21" adj gene*)).tw. (1225)
  6. (mammaprint* or (mamma* adj print*)).tw. (116)
  7. (70-gene* or ("70" adj gene*)).tw. (738)
  8. femtelle*.tw. (1)
  9. exp plasminogen activator/ or exp urokinase receptor/ or exp urokinase/ or exp plasminogen activator inhibitor 1/ or exp plasminogen activator inhibitor/ (65349)
  10. (urokinase* or (plasminogen* adj3 activator*)).tw. (35789)
  11. (upa* adj3 pai-1*).tw. (749)
  12. exp enzyme linked immunosorbent assay/ (158646)
  13. (elisa* or enzyme-linked immunosorbent assay*).tw. (145438)
  14. or/4-13 (265469)
  15. 3 and 14 (4630)
  16. Nonhuman/ not Human/ (3037332)
  17. 15 not 16 (4361)
  18. limit 17 to english language (4002)

Database: Cochrane Issue 4 of 4, Oct 2011

Search Strategy:

1

MeSH descriptor Breast Neoplasms explode all trees

7171

2

(breast* or mamma*) near/3 (neoplasm* or tumor* or tumour* or cancer* or carcinoma*):ti,ab,kw

13822

3

(#1 OR #2)

13822

4

oncotype*

13

5

21 next gene*

57

6

mammaprint* or (Mamma* next print*)

8

7

70 next gene*

15

8

femtelle*

0

9

MeSH descriptor Plasminogen Activator Inhibitor 1 explode all trees

436

10

MeSH descriptor Urokinase-Type Plasminogen Activator explode all trees

309

11

MeSH descriptor Receptors, Urokinase Plasminogen Activator explode all trees

6

12

urokinase* or (plasminogen* near/3 activator*):ti,ab,kw

3107

13

upa* near/3 pai-1*

14

14

MeSH descriptor Enzyme-Linked Immunosorbent Assay explode all trees

1849

15

elisa* or enzyme-linked immunosorbent assay*:ti,ab,kw

4149

16

(#4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15)

7269

17

(#3 AND #16)

96

 

Cochrane Reviews [1]  Other Reviews [0]   Clinical (Controlled) Trials [78]   Methods Studies [0]   Technology Assessments [9] Economic Evaluations [8]   Cochrane Groups [0]

 
   

Database: Cinahl (Accessed 12/10/2011)

Search Strategy:

1

exp BREAST NEOPLASMS/

29061

2

(breast* ADJ3 neoplasm*).ti,ab

39

3

(breast* ADJ3 tumor*).ti,ab

604

4

(breast* ADJ3 tumour*).ti,ab

119

5

(breast* ADJ3 cancer*).ti,ab

20900

6

(breast* ADJ3 carcinoma*).ti,ab

776

7

1 OR 2 OR 3 OR 4 OR 5 OR 6

31964

8

oncotype*.ti,ab

25

9

(21-gene* OR (21 ADJ gene*)).ti,ab

197

10

(mammaprint* OR (mamma* ADJ print*)).ti,ab

13

11

(70-gene* OR (70 ADJ gene*)).ti,ab

136

12

femtelle*.ti,ab

0

13

exp UROKINASE/ OR exp PLASMINOGEN ACTIVATORS/

1972

14

(urokinase* OR (plasminogen* adj3 activator*)).ti,ab

1471

15

(upa* adj3 pai-1*).ti,ab

25

16

ENZYME-LINKED IMMUNOSORBENT ASSAY/

5035

17

(elisa* OR enzyme-linked AND immunosorbent AND assay*).ti,ab

3407

18

8 OR 9 OR 10 OR 11 OR 12 OR 13 OR 14 OR 15 OR 16 OR 17

9642

19

7 AND 18

155

20

19 [Limit to: (Language English)]

153

Database: CRD databases: DARE, NHS EED, HTA (Accessed 13/10/2011)

Search Strategy:

1

MeSH DESCRIPTOR Breast Neoplasms EXPLODE ALL TREES

985

2

MeSH DESCRIPTOR Carcinoma, Ductal, Breast EXPLODE ALL TREES

16

3

(breast* near neoplasm*) OR (breast* near tumor*) OR (breast* near tumour*) OR (breast* near cancer*) OR (breast* near carcinoma*)

1471

4

(mamma* near neoplasm*) OR (mamma* near tumor*) OR (mamma* near tumour*) OR (mamma* near cancer*) OR (mamma* near carcinoma*)

10

5

#1 OR #2 OR #3 OR #4

1471

6

(oncotype*) OR (21-gene*) OR (21 near gene*)

43

7

(mammaprint*) OR (mamma* near print*) OR (70-gene*) OR (70 near gene*)

30

8

(femtelle*) OR (urokinase* near plasminogen*) OR (urokinase* near activator* ) OR (upa* near pai-1*)

32

9

MeSH DESCRIPTOR Plasminogen Activator Inhibitor 1 EXPLODE ALL TREES

2

10

MeSH DESCRIPTOR Receptors, Urokinase Plasminogen Activator EXPLODE ALL TREES

0

11

MeSH DESCRIPTOR Enzyme-Linked Immunosorbent Assay EXPLODE ALL TREES

67

12

(elisa*) OR (enzyme-linked immunosorbent assay*)

121

13

#6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12

255

14

#5 AND #13

24

Appendix COL-1 2. Inclusion/Exclusion criteria for references eligibility

[1] Eligible (YES): according Inclusion criteria (below)-INCLUDED

  1. Women diagnosed with early invasive breast cancer;
  2. The papers (publications) which include at least one of the following prognostic tests: OncotypeDX, MammaPrint und uPA/PA1 test;
  3. Papers (publications) published in English;
  4. Papers (publications) on Humans only.

[2] Unclear/No abstract (full text article is needed to make final decision)-AMBIGUOUS 

[3] NOT eligible (exclude): indicate reason for exclusion (below)-EXCLUDED

Reason for EXCLUSION? (choose any that apply)

  1. The papers (publications) did not involve women with breast cancer;  
  2. The papers (publications) did not involve at least one of the following tests: Oncotype DX , MammaPrint,  and uPA/PA1 tests;
  3. The papers (publications) published in a language other than English; 
  4. Duplicate of original publication.

Appendix COL-2 Survey across manufacturers

The manufacturers of the 3 tests (Agendia, American Diagnostica, and Genomic Health) were contacted by Agenas (lead partner of the Strand B within the EUnetHTA WP4). A list of specific questions for each test (FEMTELLE, MammaPrint, and Oncotype DX) was sent. Questions were grouped by domain; they were formulated by all the researchers involved in the project and collated by the PI of each domain. The lists of questions for the three tests are in the following pages. First contact with manufacturers was on 14 February 2012; they had 2 weeks to answer the questions (deadline was then changed after a direct request form two manufacturers). Information collected by the survey was used to answer the questions of this core HTA and reference is made as Appendix COL-2; detailed answers from manufacturers are not included in the public report.

Core HTA on Prognostic Tests for Breast Cancer

Questions for the manufacturer of the technology: FEMTELLE®, uPA/PAI-1 ELISA (American Diagnostica GmbH)

Questions about health problem and current use of the technology:

1.       In which European countries do you market your test for breast cancer recurrence?

2.       If possible, please state in which European countries your test is most widely used.

3.       If possible, please state how many tests are sold in each country.

Questions about technical description and characteristics of the technology:

4.       How much time has to be allowed for shipping the samples?

5.       Are the equipment and supplies required for the specimen preparation commonly available by the cancer centres / hospitals across EU?

6.       Are there particular qualification, training and quality assurance needed for sample isolation and preparation?

7.       What kind of qualification, training and quality assurance are needed for those centres that decide to perform the test in their own labs?

Questions about safety issues:

8.       What are the safety standards that the technology must follow (e.g. UNI, ISO)?

9.       What is the statistical, percentage of sampling error?

10.   What systems are used to minimise or eliminate the risk of the sample contamination?

11.   Is there a product data sheet, application for product license, safety reports or other documentation of the products including safety information available for us?

12.   Are there technology or patient registries managed by the manufacturer regarding the test in question?

13.   Are you aware of discussion forums, in professional or patient organizations, or in social media, about your product?

Questions about clinical effectiveness of the technology:

14.   Are you aware of any unpublished study?

Especially with prospective design, reporting on clinical effectiveness, clinical utility, health outcomes (morbidity, mortality), safety (adverse events according adjuvant chemotherapy), quality of life, clinical decision making on treatment choice with adjuvant chemotherapy, patients satisfactions, overall benefit and harms in health outcomes, in comparison of standard (or current) care, or direct (head-to-head) comparison.

Questions about market and regulation:

15.   In which European country is your test reimbursed by the National Health Service?

 16.   In which European country is your test subject to price control?

 17.   In which European country is your test subject to acquisition regulation?

 18.   Is the marketing of genetic tests for breast cancer to the patients restricted?

 Questions about prices:

19.   At what price do you sell the test?

 20.   Are the prices different among countries? If yes, please specify the price for each EU country.

Please could you help us produce a factually correct, fair and balanced report by providing the information requested from your own databases if the information exists.

Core HTA on Prognostic Tests for Breast Cancer

Questions for the manufacturer of the technology: MammaPrint® (Agendia BV)

Questions about health problem and current use of the technology:

1.       In which European countries do you market your test for breast cancer recurrence?

2.       If possible, please state in which European countries your test is most widely used.

3.       If possible, please state how many tests are sold in each country.

Questions about technical description and characteristics of the technology:

4.       What are the clinicopathological factors that need to be considered together with the test results?

5.       How much time has to be allowed for shipping the samples?

6.       Are the equipment and supplies required for the specimen preparation commonly available by the cancer centres / hospitals across EU?

7.       Are there particular qualification, training and quality assurance needed for sample isolation and preparation?

Questions about safety issues:

8.       What are the safety standards that the technology must follow (e.g. UNI, ISO)?

9.       What is the statistical, percentage of sampling error?

10.   What systems are used to minimise or eliminate the risk of the sample contamination?

11.   Is there a product data sheet, application for product license, safety reports or other documentation of the products including safety information available for us?

12.   Are there technology or patient registries managed by the manufacturer regarding the test in question?

13.   Are you aware of discussion forums, in professional or patient organizations, or in social media, about your product?

Questions about clinical effectiveness of the technology:

14.   Are you aware of any unpublished study?

Especially with prospective design, reporting on clinical effectiveness, clinical utility, health outcomes (morbidity, mortality), safety (adverse events according adjuvant chemotherapy), quality of life, clinical decision making on treatment choice with adjuvant chemotherapy, patients satisfactions, overall benefit and harms in health outcomes, in comparison of standard (or current) care, or direct (head-to-head) comparison.

Questions about market and regulation:

15.   In which European country is your test reimbursed by the National Health Service?

16.   In which European country is your test subject to price control?

17.   In which European country is your test subject to acquisition regulation?

18.   Is the marketing of genetic tests for breast cancer to the patients restricted?

Questions about prices:

19.   At what price do you sell the test?

20.   Are the prices different among countries? If yes, please specify the price for each EU country.

Please could you help us produce a factually correct, fair and balanced report by providing the information requested from your own databases if the information exists.

Core HTA on Prognostic Tests for Breast Cancer

Questions for the manufacturer of the technology: Oncotype DX™ (Genomic Health, Inc.)

Questions about health problem and current use of the technology:

1.       In which European countries do you market your test for breast cancer recurrence?

2.       If possible, please state in which European countries your test is most widely used.

3.       If possible, please state how many tests are sold in each country.

Questions about technical description and characteristics of the technology:

4.       How much time has to be allowed for shipping the samples?

5.       Are the equipment and supplies required for the specimen preparation commonly available by the cancer centres / hospitals across EU?

6.       Are there particular qualification, training and quality assurance needed for sample isolation and preparation?

Questions about safety issues:

7.       What are the safety standards that the technology must follow (e.g. UNI, ISO)?

8.       What is the statistical, percentage of sampling error?

9.       What systems are used to minimise or eliminate the risk of the sample contamination?

10.   Is there a product data sheet, application for product license, safety reports or other documentation of the products including safety information available for us?

11.   Are there technology or patient registries managed by the manufacturer regarding the test in question?

12.   Are you aware of discussion forums, in professional or patient organizations, or in social media, about your product?

Questions about clinical effectiveness of the technology:

13.   Are you aware of any unpublished study?

Especially with prospective design, reporting on clinical effectiveness, clinical utility, health outcomes (morbidity, mortality), safety (adverse events according adjuvant chemotherapy), quality of life, clinical decision making on treatment choice with adjuvant chemotherapy, patients satisfactions, overall benefit and harms in health outcomes, in comparison of standard (or current) care, or direct (head-to-head) comparison.

Questions about market and regulation:

14.   In which European country is your test reimbursed by the National Health Service?

15.   In which European country is your test subject to price control?

16.   In which European country is your test subject to acquisition regulation?

17.   Is the marketing of genetic tests for breast cancer to the patients restricted?

Questions about prices:

18.   At what price do you sell the test?

19.   Are the prices different among countries? If yes, please specify the price for each EU country.

Please could you help us produce a factually correct, fair and balanced report by providing the information requested from your own databases if the information exists.

Appendix COL-3 Survey Report for retrieving information on the use of technology in European countries

pdf113.COL Appendix 3

Appendix COL-4 Abbreviations list

  • AE assessment element
  • AGO German Working Group for Gynecological Oncology
  • ASCO American Society of Clinical Oncology
  • BMI  body mass index
  • CHT chemotherapy plus hormonal therapy
  • CLIA Clinical Laboratory Improvement Amendments
  • COLMOD 1 collaborative model 1
  • CUR Health Problem and Current Use domain
  • DCIS ductal carcinoma in situ
  • DCS decisional conflict scale
  • DFS disease-free survival
  • ECO Costs and economic evaluation domain
  • EFF Effectiveness domain
  • EGAPP Evaluation of Genomic Applications in Practice and Prevention
  • ELISA enzyme-linked immunoassay
  • EMA European Medicines Agency
  • ER+, ER- oestrogen receptor positive, negative
  • ESIS European chemical Substances Information System
  • ETH Ethical domain
  • EU European Union
  • EU-OSHA European Agency for Safety and Health at Work
  • FDA US Food and Drug Administration
  • FFPE formalin fixed and paraffin embedded
  • HER2 human epidermal growth factor receptor 2
  • HRT hormone replacement therapy
  • HT hormonal therapy
  • HTA health technology assessment
  • IARC International Agency for Research on Cancer
  • IPCS International Programme on Chemical Safety
  • IVD in vitro diagnostic
  • JA1 First EUnetHTA Joint Action
  • LCIS lobular carcinoma in situ
  • LEG Legal aspects domain
  • LN+ LN- lymph node negative
  • MSDS Material Safety Data Sheets
  • NCCN National Comprehensive Cancer Network
  • NPI Nottingham Prognostic Index
  • OECD Organisation for Economic Co-operation and Development
  • OELs occupational exposure limits
  • ORG Organisational aspects domain
  • OS overall survival
  • PAI-1 plasminogen activator inhibitor 1
  • PET` positron emission tomography
  • PMA pre-market approval
  • PTBCR prognostic tests for breast cancer recurrence
  • RCT randomised controlled trials
  • REACH Registration, Evaluation, Authorisation and Restriction of Chemical substances
  • RS recurrence score
  • RT–PCR reverse transcriptase –polymerase chain reaction
  • SAF Safety domain
  • SAG Stakeholder Advisory Group
  • SOC Social aspects domain
  • STAI state or situational anxiety
  • TEC Description and technical characteristics domain
  • TNM tumour, node, metastasis
  • TWA time-weighted average
  • uPA urokinase plasminogen activator
  • WP4 Work Package 4
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