PUBLIC HEALTH CLASSICS

 

Revisiting Wilson and Jungner in the genomic age: a review of screening criteria over the past 40 years

 

 

Anne AndermannI,1; Ingeborg BlancquaertII; Sylvie BeauchampII; Véronique DéryIII

IWorld Health Organization, 20 avenue Appia, 1211 Geneva 27, Switzerland
IIQuebec Agency for Health Technology Assessment (AETMIS), Montreal, QC, Canada
IIISt Justine Hospital, Montreal, QC, Canada

 

 

At the time when Wilson and Jungner wrote their report, there were many technological advances in medicine, which made screening a topic of growing importance and controversy. With the recent sequencing of the entire human genome,2,3 screening is re-emerging as a timely issue. Genetic screening is being proposed as a major vehicle for translating genetic and genomic advances into population health gains.4,5 However, the ever-widening gap between what is technologically possible and the services available is creating pressure to introduce or expand screening programmes, often before adequate safeguards and regulatory frameworks are in place.6,7

The main difficulty, as observed by Wilson and Jungner in 1968, was that "in theory, screening is an admirable method of combating disease ... [but] in practice, there are snags".1 In their landmark publication, the authors were fundamentally preoccupied with the notion that:

"The central idea of early disease detection and treatment is essentially simple. However, the path to its successful achievement (on the one hand, bringing to treatment those with previously undetected disease, and, on the other, avoiding harm to those persons not in need of treatment) is far from simple though sometimes it may appear deceptively easy."

For this reason, Wilson and Jungner attempted to define screening criteria to guide the selection of conditions that would be suitable for screening, based, among other factors, on the capacity to detect the condition at an early stage and the availability of an acceptable treatment (Box 1). They considered these criteria "especially important when case-finding is carried out by a public health agency, where the pitfalls may be more numerous than when screening is performed by a personal physician".

 

 

Just as forty years ago, Wilson and Jungner wrote their treatise amidst a great deal of controversy surrounding the early detection of disease, there are now similar debates with respect to genetic screening. A growing number of diseases can now be detected in the pre-clinical stage, and even in the pre-pathological stage, using molecular and non-molecular diagnostic techniques.

Large-scale screening for genetic conditions began around the time of the Wilson and Jungner publication. There was newborn screening for inborn errors of metabolism such as phenylketonuria, later followed by prenatal screening for Down syndrome and neural tube defects using ultrasound and biochemical markers. Once individual disease genes started to be identified using novel molecular techniques, pilot screening programmes were established for several rare genetic conditions such as Tay Sachs disease and cystic fibrosis. With the advances in genetic technology, the rate at which new disease genes are being identified is out-pacing the ability of professionals and policy-makers to assess the potential benefits and pitfalls of introducing or expanding genetic screening programmes.8–10

Due to the complexity involved in genetic screening policy-making, many advocate the use of criteria. The Wilson and Jungner criteria have long been considered the gold standard in making such decisions.11–13 However, a growing number of approaches to genetic screening policy-making are in use,14,15 based on an even greater number of different sets of criteria.16–19 Many are variations on the classic criteria of Wilson and Jungner. However, when different jurisdictions use diverse methods of decision-making for the same screening decisions, it can lead to inconsistencies: "The lack of even broad concordance at the level of national policy is extremely disturbing. Though all discussion is nominally founded on the ten principles laid down by Wilson and Jungner in 1968, there seems no generally accepted way of using these principles, or derived criteria, as objective decision tools."20

Even when the same criteria are used, these have at times been criticized for being too vague or theoretical,21 and thus difficult to assess in a consistent manner.22,23 Furthermore, even when criteria are met, there may still be logistical, social or ethical reasons that preclude screening.24 Research is therefore needed to determine which criteria should be used and what processes are required to ensure that new and expanded genetic screening programmes best serve the public interest.

As part of a larger research programme,25 a series of literature reviews and consultations were used to develop a systematic and transparent approach for guiding genetic screening policy decisions. The initial step involved a literature review to systematically identify and synthesize over 50 lists of screening criteria that have been proposed over the past 40 years. The majority of these criteria overlap with the classic Wilson and Jungner criteria, particularly with regard to screening for health conditions at an early stage, where there exist effective interventions to improve outcomes compared to standard care. However, several adaptations have been made to the classic criteria, and several new criteria have also emerged (Box 2). Many adaptations of classic criteria reflect issues raised by the growing interest in genetic screening (e.g. the importance of serious genetic conditions even if they are rare, implications of genetic information for family members, need for analytical and clinical validity of screening tests, possibility of interventions that offer reproductive options, etc.). In contrast, many of the emerging criteria reflect broader trends that have shaped both Western medicine and society more generally over the past generation (e.g. increased consumerism, the shift away from paternalism towards informed choice, a focus on evidence-based health care, and the rise of managed care models that emphasize cost-effectiveness, quality assurance, and accountability of decision-makers).

 

 

Following a series of consultations with local and international stakeholders and experts, the modified Wilson and Jungner criteria and newly emerging criteria transformed into a more elaborate decision support guide.25 The guide consists of three levels of analysis that contribute to integrating various types of scientific and contextual evidence, making explicit the iterative nature of decision-making, balancing different perspectives (e.g. individual versus population viewpoints), comparing various alternatives (e.g. different screening strategies as compared to routine clinical care), considering whether implementation in a given context will allow the benefits of the screening programme to be realized, and emphasizing that adequate governance and regulatory frameworks are required. This approach to screening policy-making encourages documentation of evidence, trade-offs, and the reasoning underpinning recommendations, thus promoting greater transparency, and allowing decisions to be revisited over time.

Ultimately, the decisions to develop, implement and continue to fund genetic screening programmes are political.26 On the one hand, governments want to support the biotechnology sector which provides jobs and fuels the economy, while on the other hand, governments are also responsible for organizing health services and protecting consumers.27 Although genetic services and screening programmes aim to improve the health of the population, there is growing concern that the increasing number of genetic tests becoming available at lower costs could compromise the viability of the health care system. Even though the tests themselves may be inexpensive and suitable for large-scale use, the infrastructure and human resources needed to provide appropriate education, counselling, interventions and follow-up are likely to be far more costly. When it comes to the allocation of scarce resources, economic considerations must be considered alongside "notions of justice, equity, personal freedom, political feasibility, and the constraints of current law".28,29

Governments are therefore faced with the difficult task of managing the use of new genetic information and technologies while balancing the many different perspectives and needs of society. Even beyond the field of genetics and genomics, there is a growing understanding that population-level policy decisions should be based both on high quality evidence and on the values of the population,30,31 as well as contextual considerations.32,33

The criteria of Wilson and Jungner are still upheld today as "classics",34 the "gold standard of screening assessment",35 having "stood well the test of time".36 However, the authors never expected their criteria to remain unchanged over time, but rather hoped that their publication would provoke further reflection and debate in this complex area:
"If anywhere we have appeared dogmatic, we hope this may serve to stimulate discussion, since, in the end, real development depends on an exchange of views."

Indeed, an exchange of views has occurred over the last four decades, and many other authors have attempted to adapt or reinvent the Wilson and Jungner criteria to better fit within their particular context of screening and with the changing times. In particular, a great deal has been written with regard to screening criteria as applied to the rapidly growing field of genetics. Although the value of the Wilson and Jungner criteria remains undisputed to this day, newer policy tools are now available,25 bringing new life to the longstanding debate that Wilson and Jungner started on how best to tackle perennial challenges relating to screening policy decisions.

 

Acknowledgements

The authors would like to thank the members of APOGEE-Net, a knowledge network to assist policy-making in genetics funded by the Canadian Institutes of Health Research (CIHR), the staff of the Quebec Agency for Health Technology Assessment (AETMIS) who contributed to this work, as well as the numerous experts, patient group representatives and policy-makers who generously donated their time to participate in various consultations.

Competing interests: None declared.

 

References

1. Wilson JMG, Jungner G. Principles and practice of screening for disease. Geneva: WHO; 1968. Available from: http://www.who.int/bulletin/volumes/86/4/07-050112BP.pdf         

2. Lander ES, Linton LM, Birren B, Nussbaum C, Zody MC, Baldwin J, et al. Initial sequencing and analysis of the human genome. Nature 2001;409:860-921. PMID:11237011 doi:10.1038/35057062         

3. Venter JC, Adams MD, Meyers EW, Li PW, Mural RJ, Sutton GG, et al. The sequence of the human genome. Science 2001;291:1304-51. PMID:11181995 doi:10.1126/science.1058040         

4. Bell J. The new genetics in clinical practice. BMJ 1998;316:618-20. PMID:9518921         

5. Khoury MJ, McCabe LL, McCabe ER. Population screening in the age of genomic medicine. N Engl J Med 2003;348:50-8. PMID:12510043 doi:10.1056/NEJMra013182        

6. Knoppers BM, Hirtle M, Glass KC. Commercialization of genetic research and public policy. Science 1999;286:2277-8. PMID:10636788 doi:10.1126/science.286.5448.2277         

7. Kaufert PA. Health policy and the new genetics. Soc Sci Med 2000;51:821-9. PMID:10972427 doi:10.1016/S0277-9536(00)00063-0        

8. Ojha RP, Thertulien R. Health care policy issues as a result of the genetic revolution: Implications for public health. Am J Public Health 2005;95:385-8. PMID:15727963 doi:10.2105/AJPH.2003.026708         

9. Genetic testing: Policy issues for the new millennium. Paris: Organization for Economic Cooperation and Development (OECD); 2000.         

10. Genetic screening: a supplement to the 1993 report by the Nuffield Council on Bioethics. London: Nuffield Council on Bioethics; 2006.         

11. Burke W, Coughlin SS, Lee NC, Weed DL, Khoury MJ. Application of population screening principles to genetic screening for adult-onset conditions. Genet Test 2001;5:201-11. PMID:11788085 doi:10.1089/10906570152742245        

12. Goel V. Appraising organised screening programmes for testing for genetic susceptibility to cancer. BMJ 2001;322:1174-8. PMID:11348918 doi:10.1136/bmj.322.7295.1174         

13. Zimmern R, Cook C. The Nuffield Trust Genetics Scenario Project. Genetics and health: policy issues for genetic science and their implications for health and health services. London: The Stationery Office; 2000.        

14. Sherriff R, Best L, Roderick P. Population screening in the NHS: A systematic pathway from evidence to policy formulation. J Public Health Med 1998;20:58-62. PMID:9602450         

15. Walters L. A national advisory committee on genetic testing and screening. In: Annas GJ and Elias S, eds. Gene mapping: Using law and ethics as guides. New York: Oxford University Press; 1992: 255-66.        

16. Criteria for appraising the viability, effectiveness and appropriateness of a screening programme. London: National Screening Committee, UK; 2003.         

17. Serving the family from birth to the medical home. Newborn screening: A blueprint for the future, a call for a national agenda on state newborn screening programs. Pediatrics 2000;106:389-427. PMID:10947682         

18. Genetic screening. The Hague: Health Council of the Netherlands, Committee on Genetic Screening; 1994.         

19. Genetic screening: programs, principles and research. National Research Council, Committee for the Study of Inborn Errors of Metabolism. Washington, DC: National Academy of Sciences; 1975.        

20. Pollitt RJ. International perspectives on newborn screening. J Inherit Metab Dis 2006;29:390-6. PMID:16763907 doi:10.1007/s10545-006-0259-2         

21. Pollitt RJ. Principles and performance: assessing the evidence. Acta Paediatr (Suppl) 1999;88:110-4. doi:10.1080/080352599750029538         

22. Grosse SD, Boyle CA, Botkin JR, Comeau AM, Kharrazi M, Rosenfeld M, et al. Newborn screening for cystic fibrosis: Evaluation of benefits and risks and recommendations for state newborn screening programs. MMWR 2004;53 RR13;1-36.         

23. Lindegren ML, Kobrynski L, Rasmussen S, Moore CA, Grosse SD, Vanderford ML et al. Applying public health strategies to primary immunodeficiency diseases: a potential approach to genetic disorders. MMWR (Recomm Rep) 2004;53 RR01;1-29. PMID:14724556         

24. Eijkelkamp EJ, Yapp TR, Powell LW. HFE-associated hereditary hemochromatosis. Can J Gastroenterol 2000;14:121-5. PMID:10694284         

25. Andermann A, Beauchamp S, Costea I, Blancquaert I, Dery V. Guiding policy decisions for population-based genetic screening: an evidence-based and interdisciplinary approach. Submitted.        

26. Muir Gray JA. Evidence based policy making. BMJ 2004;329:988-9. PMID:15514318 doi:10.1136/bmj.329.7473.988         

27. McDonald M. Biotechnology, ethics and government: A synthesis. Prepared for The Canadian Biotechnology Advisory Committee, Project Steering Committee on Incorporating Social and Ethical Considerations into Biotechnology. Ottawa: CBAC; 2000.         

28. Graham JD, Corso PS, Morris JM, Segui-Gomez M, Weinstein MC. Evaluating the cost-effectiveness of clinical and public health measures. Annu Rev Public Health 1998;19:125-52. PMID:9611615 doi:10.1146/annurev.publhealth.19.1.125         

29. Buchanan A, Brock DW, Daniels N, Wikler D. From chance to choice: genetics and justice. Cambridge: Cambridge University Press; 2000.         

30. Lin V, Gibson B, eds. Evidence-based health policy: problems and possibilities. Melbourne: Oxford University Press; 2003.        

31. Kahn P. Role of public policy in genetic screening and counseling. In: Bartels DM, LeRoy BS, Caplan AL, eds. Prescribing our future: ethical challenges in genetic counseling. New York: Aldine de Gruyter; 1993. pp.79-87.         

32. Banta HD & European Advisory Committee on Health Research, World Health Organization Regional Office for Europe. Considerations in defining evidence for public health. Int J Technol Assess Health Care 2003;19:559-72. PMID:12962344 doi:10.1017/S0266462303000515         

33. Dobrow MJ, Goel V, Lemieux-Charles L, Black NA. The impact of context on evidence utilization: A framework for expert groups developing health policy recommendations. Soc Sci Med 2006;63:1811-24. PMID:16764980 doi:10.1016/j.socscimed.2006.04.020         

34. Hall DM, Stewart-Brown S. Screening in child health. Br Med Bull 1998; 54:929-43. PMID:10367424         

35. Linnane E, Paul A, Parry R. Screening of newborn infants for cholestatic hepatobiliary disease. Does test fulfil screening criteria? BMJ 1999;319:1435. PMID:10574881         

36. Population cancer screening in Canada: strategic priorities. Ottawa: Canadian Strategy for Cancer Control; 2002        

 

 

(Submitted: 3 December 2007 – Accepted: 22 January 2008)

 

 

Almost 40 years ago, WHO commissioned a report on screening from James Maxwell Glover Wilson, then Principal Medical Officer at the Ministry of Health in London, England, and Gunner Jungner, then Chief of the Clinical Chemistry Department of Sahlgren's Hospital in Gothenburg, Sweden. The report1, published in 1968, was entitled: Principles and practice of screening for disease and it has since become a public health classic.
1 Correspondence to Anne Andermann (e-mail: andermanna@who.int).
doi:10.2471/BLT.07.050112

World Health Organization Genebra - Genebra - Switzerland
E-mail: bulletin@who.int