i Points to consider for prioritizing clinical genetics services. Results from a European consensus process oriented at the principles of Accountability for Reasonableness Franziska Severin 1 , Pascal Borry 2 , Martina Cornel, 3 Florence Fellmann 4 , Shirley Victoria Hodgson 5 , Heidi Howard 6 , Jürgen John 1 , Hülya Kayserili 7 , Florian Koerber 1 , Mark Kroese 8 , Celine Lewis 9 , Georg Marckmann 10 , Peter Meyer 11,12 , Jörg Schmidtke 13 , Heather Skirton 14 , Wolf Rogowski 1,15 for the EuroGentest and ESHG / PPPC Priority Consortium 1. Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany 2. Centre for Biomedical Ethics and Law, Katholieke Universiteit Leuven, Box 7001, Kapucijnenvoer 35/3, Leuven 3000, Belgium. 3. Department of Clinical Genetics, Section Community Genetics, EMGO Institute for Health and Care Research, VU University Medical Center Amsterdam, the Nether- lands 4. Service de Génétique Médicale, CHUV, 1011 Lausanne, Switzerland 5. Department of Medical Genetics, St George’s University of London, London, UK 6. Department of Epidemiology and Analyses in Public Health, UMR 1027, Inserm, Toulouse, France 7. Department of Medical Genetics, Istanbul Medical Faculty, Istanbul University, Istan- bul, Turkey 8. PHG Foundation, 2 Worts Causeway, Cambridge CB1 8RN, UK 9. Genetic Alliance UK, Unit 4D, Leroy House, 436 Essex Road, London N1 3QP, UK 10. Institute for Ethics, History and Theory of Medicine, Ludwig Maximilians University, Lessingstr. 2, D-80336 Munich, Germany 11. Human Genetics Foundation, Munich, Germany 12. University Medicine, Institute for Medical Genetics, Rostock, Germany 13. Hannover Medical School, Department of Human Genetics, Hannover, Germany 14. School of Nursing and Midwifery, Faculty of Health, Education and Society Plymouth University Wellington Rd Taunton TA1 5YD, UK 15. Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Clinical Center, Ludwig Maximilians University, Ziemssenstraße 1, 80336 Munich, Germany; Tel. +49-89-3187-4128; Fax +49-89-3187-3375; rogowski@helmholtz- muenchen.de (corresponding author)
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Points to consider for prioritizing clinical genetics services. Results from a European
consensus process oriented at the principles of Accountability for Reasonableness
Franziska Severin1, Pascal Borry2, Martina Cornel,3 Florence Fellmann4, Shirley Victoria
Hodgson5, Heidi Howard6, Jürgen John1, Hülya Kayserili7, Florian Koerber1, Mark Kroese8,
Celine Lewis9, Georg Marckmann10, Peter Meyer11,12, Jörg Schmidtke13, Heather Skirton14,
Wolf Rogowski1,15 for the EuroGentest and ESHG / PPPC Priority Consortium
1. Helmholtz Zentrum München, German Research Center for Environmental Health
2. Centre for Biomedical Ethics and Law, Katholieke Universiteit Leuven, Box 7001,
Kapucijnenvoer 35/3, Leuven 3000, Belgium.
3. Department of Clinical Genetics, Section Community Genetics, EMGO Institute for
Health and Care Research, VU University Medical Center Amsterdam, the Nether-
lands
4. Service de Génétique Médicale, CHUV, 1011 Lausanne, Switzerland
5. Department of Medical Genetics, St George’s University of London, London, UK
6. Department of Epidemiology and Analyses in Public Health, UMR 1027, Inserm,
Toulouse, France
7. Department of Medical Genetics, Istanbul Medical Faculty, Istanbul University, Istan-
bul, Turkey
8. PHG Foundation, 2 Worts Causeway, Cambridge CB1 8RN, UK
9. Genetic Alliance UK, Unit 4D, Leroy House, 436 Essex Road, London N1 3QP, UK
10. Institute for Ethics, History and Theory of Medicine, Ludwig Maximilians University,
Lessingstr. 2, D-80336 Munich, Germany
11. Human Genetics Foundation, Munich, Germany
12. University Medicine, Institute for Medical Genetics, Rostock, Germany
13. Hannover Medical School, Department of Human Genetics, Hannover, Germany
14. School of Nursing and Midwifery, Faculty of Health, Education and Society Plymouth
University Wellington Rd Taunton TA1 5YD, UK
15. Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine, Clinical Center, Ludwig Maximilians University, Ziemssenstraße 1, 80336 Munich, Germany; Tel. +49-89-3187-4128; Fax +49-89-3187-3375; [email protected] (corresponding author)
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ABSTRACT [MAXIMUM WORD COUNT FOR ABSTRACT: 250] .........................................................................III BACKGROUND...............................................................................................................................................1 METHODS .....................................................................................................................................................3
RESULTS ........................................................................................................................................................5 SCOPE AND CONTEXT OF PRIORITIZATION OF GENETIC TESTS ............................................................................................. 5 RELEVANT CRITERIA FOR PRIORITIZING GENETIC TESTS ..................................................................................................... 7
Health need .................................................................................................................................................... 7 Severity of the disease................................................................................................................................................. 7 Progression of disease ................................................................................................................................................. 8 Likelihood of disease.................................................................................................................................................... 8
Intervention need / Medical benefit............................................................................................................... 9 Medical benefit for the tested individual .................................................................................................................... 9 Non‐medical benefit for the tested individual........................................................................................................... 10 Benefit for family members ....................................................................................................................................... 11 Time window to obtain benefit ................................................................................................................................. 11
Costs ............................................................................................................................................................. 12 ESTABLISHING THE RELATIVE IMPORTANCE OF CRITERIA ................................................................................................. 13 HOW TO USE THIS PRIORITIZATION FRAMEWORK .......................................................................................................... 14
DISCUSSION ................................................................................................................................................15 IMPLICATIONS FOR FUTURE PRIORITIZATION ACTIVITIES.................................................................................................. 15
Genetic exceptionalism for prioritization? ................................................................................................... 15 Using accountability for reasonableness for prioritization........................................................................... 17
IMPLICATIONS FOR FURTHER RESEARCH ...................................................................................................................... 17 CONCLUSION ........................................................................................................................................................ 19
Kent, Christine Patch, Mark Kroese, Shirley Victoria Hodgson, Florian Koerber, Franziska
Severin. Furthermore, we are grateful to further colleagues for their scientific feedback, in
particular Norman Daniels.
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The research is carried out on behalf of the Helmholtz Center Munich – German Research
Center for Environmental Health. The Helmholtz Center is an independent organization fund-
ed by the German and Bavarian government. This study was supported by EuroGentest (Eu-
roGentest 2, Unit 2: Genetic testing as part of health care, Work package 6 (W.H. Rogowski),
grant number Health-F4-2010-261469). It was further supported by the grant “Individualized
Health Care: Ethical, Economic and Legal Implications for the German Health Care System”
of the German Federal Ministry of Education and Research (BMBF, grant number
01GP1006B).
The authors declare no conflict of interests with regards to this project.
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Table 1: Points to consider for prioritizing genetic tests
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Criterion Explanation Selected challenges for measurement and use Severity Tests for conditions with a severe impact on the patient’s
health should be of higher priority than tests for compara‐tively mild diseases.
Severity can be expressed in reduced life expectancy or in reduced health related quality of life. Methodological details of measuring severity need to be considered because they can cause concerns, e.g. if QALYs are used.
Progression Tests for conditions which may already have developed silently or even overtly in the tested individual should be of higher priority than predictive tests in healthy individu‐als before the onset of disease.
Needs to be applied in context‐dependent manner: • At a certain stage of progression clinical signs and symptoms may be more accurate and make genetic testing obsolete.
• May be inversely related to medical benefit if benefit primarily arises from prevention in healthy or presymptomatic carriers. H
ealth ne
ed
Likelihood Tests for patients with high a‐priori risk of developing the disease (e.g. high‐risk populations or even first‐degree relatives) should be of higher priority than tests for pa‐tients with low a‐priori risk.
• Incomplete penetrance, i.e. a low probability of overt symptoms needs to be incorporated in risk assessment.
• High‐risk individuals may be more likely to be detected as genetic cases in clinical practice than medium‐risk individuals
Medical ben‐efit
Tests where, based on the results, effective clinical treat‐ment or prevention options exist, should be of higher pri‐ority than tests without effective interventions.
• For rare diseases and long‐benefit, evidence frequently is weak. • Individual behavior patterns (e.g. whether the treatment would be pur‐sued) need to be accounted for to establish the benefit of a genetic test.
Non‐medical benefit
Consideration of intervention need also should include benefit of health‐related information by itself which may assist individuals and families in planning their life.
• There is a need for more scientific evidence about the benefit for life de‐cision making (“empowerment”) incurred by different genetic tests.
• It is unclear how non‐actionable information should be accounted for. Benefit for family mem‐bers
Consideration of intervention need also should include benefits for family members.
• Also, the non‐medical benefits may apply to relatives. • Particularly for tests because of non‐medical benefits, trade‐offs with concerns for privacy or the right not to know may be relevant. In
terven
tion
need
Time window It may be that the benefit from a test can only be obtained within a finite time window.
Criterion likely to be of higher relevance for a local perspective which also includes management issues than from a health care system perspective.
Costs
Costs Tests with lower costs (and, thus, less other tests dis‐placed) should be of higher priority than high cost tests.
• Consideration of costs should include savings elsewhere in health care. • Further evidence from well‐designed economic evaluations are needed. • Costs should not be the dominant but only one criterion among others.
Weighing the criteria
Typically, tests differ across different criteria simultaneously so that the criteria need to be weighted. A score based on empirical meth‐ods of measuring and weighting the criteria would be desirable. However, currently, it is too premature for such quantitative ranking algorithm, e.g. because of too limited evidence about whether the criteria are met and unresolved questions about which value judg‐ments should be incorporated into the empirical analysis.
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Appendix Table 1: Workshop Participants
Country Name Role Email Organisation
Germany Wolf Rogowski Chair [email protected] Helmholtz Zentrum München