Education and debate

Appraising organised screening programmes for testing for genetic susceptibility to cancer

Vivek Goel, associate professor and chair,  for Crossroads 99 Group.

Department of Health Administration, McMurrich Building, Toronto, Ontario, Canada M5S 1A8

vivek.goel{at}utoronto.ca

Public health officials rely on criteria developed by Wilson and Jungner for assessing whether or not to implement population screening programmes. These criteria were developed over 30 years ago, when screening primarily focused on detecting early stages or precursors of chronic disease. With the introduction of testing for genetic susceptibility, particularly for cancer, it is important to assess whether these criteria can continue to be applied in the decision making process. We report on a workshop that assessed criteria for population screening in the context of testing for genetic susceptibility to cancer.

Many criteria for the evaluation of screening programmes have been proposed, ^{1 2} and most are similar to those proposed by Wilson and Jungner in a 1968 World Health Organization report.³ The criteria are based on a simple linear model of disease progression (figure) in which screening tests primarily detect a preclinical asymptomatic phase.

The continuum of screening has expanded to include a range of other states. The figure illustrates another model for screeningscreening for risk factors or susceptibility, the detection of risk factors for disease⁴ (such as blood pressure or cholesterol concentration), or the identification, through the detection of genetic markers, of individuals who have increased susceptibility to disease.⁵ Separate consideration of these forms of screening is important as the type of interventions that can be offered to individuals who have positive test results can differ: treatment in the case of traditional screening, interventions to modify the risk factor, or counselling if susceptibility is identified. Thus, the criteria for evaluating programmes at the population level for such tests could differ.

Is it premature to discuss criteria for organised screening programmes for testing for genetic susceptibility to cancer? We consider that it is better to have a discussion about such criteria now, before such tests become widely adopted. ^{6 7} We report on the Crossroads 99 conference, held in Toronto, Canada, in October 1999, in conjunction with an international symposium examining the ethical, legal, and sociobehavioural implications of notification of risk of breast, ovarian, and colorectal cancer. The workshop participants included consumers, healthcare providers (clinical geneticists, genetics counsellors, medical, surgical, and radiation oncologists, public health specialists, psychologists, psychiatrists, nurses, social workers, and primary care physicians), researchers (basic scientists, epidemiologists, social scientists), lawyers, and ethicists.

View larger version (28K): [in this window] [in a new window]   Screening pathways compared over simplified natural course of disease. Traditional screening identifies early stage disease or precursors to disease. Susceptibility screening moves the process earlier and identifies risk of disease in individuals who are healthy. Thus resulting interventions aim to reduce risk of disease developing rather than trying to reduce severity or consequences of disease

The objective was to develop a consensus on a framework to be used for introducing population based screening programmes based on notification of risk for cancer. An explicit purpose was to ensure that the framework examined ethical, legal, social, and economic implications and could be applied to current and future tests for susceptibility.

	Method

The Wilson and Jungner 1968 framework (table 1) for evaluating screening tests was presented as an example of a type of framework, but workshop participants were not bound to follow its structure or content. The workshop proceeded in three steps: identification of the domains or the major category headings for the framework; identification of criteria or the specific items within each domain; and prioritisation and selection of the criteria.

The workshop participants worked in multidisciplinary groups that identified key domains and criteria. Common themes from the groups were identified and the resulting model reviewed in a plenary session.

	Results

The overall thrust of the Wilson and Jungner framework was strongly agreed with, although there was some broadening of the domains and criteria. The consensus was that ethical, legal, and social issues should be dealt with across all the domains, rather than treating them separately. These issues were viewed as essential for all considerations involving a screening programme. Creation of a separate category for them could lead to their being marginalised.

The participants also recommended that all screening programmes should observe the basic universal principles of human rights, such as those in the convention on human rights and biomedicine.⁸ This statement covers the primacy of the human being, equitable access to health care, privacy, right to information, non-discrimination, and use of predictive genetic tests. Considerations about new screening technologies and programmes that seek to apply them should pay attention to such fundamental principles.

Knowledge of population and disease
Table 1 lists the original and revised framework. The first domain has been broadened to include characteristics of the population. This acknowledges that in testing for susceptibility it is important not only to understand the disease but also the population that is to be tested. The first criterion is essentially unchanged except the more commonly used term "burden of disease" is used. The burden ultimately being considered should be that of the disease to be prevented, not the condition or marker status that is being screened for. For example, in genetic screening for ovarian cancer it is the incidence and prevalence of ovarian cancer that is important in determining burden, not the prevalence of the marker status for the condition. An analogy may be drawn with cholesterol screening, in which "hypercholesterolaemia" is often labelled as disease. The prevalence of this state is far greater than that of the target conditions such as heart disease.

Feasibility of screening procedures
This domain's title has been expanded, although the basic concepts are unchanged. Screening procedures involve more than the test alone. They include a range of activities from identification of the target population to recruitment, counselling, informed consent, administration of the actual test, and communication of the results.

Interventions and follow up
This domain underwent considerable expansion, although the criteria are conceptually the same. Rather than considering only treatments for disease we consider a range of interventions and follow up strategies. The evaluations of these interventions should examine social and psychological aspects as well as physical aspects. The interventions need to have demonstrable net benefit on these dimensions. For example, prophylactic mastectomy may be an effective intervention for reducing risk of cancer in carriers of the BRCA mutation, but evidence would also be required on its psychological impact. Physical benefits would need to be traded off against potential adverse psychological or social effects.

Societal and health system issues
The last category of the original framework examined costs. We propose expansion to societal and health system issues. A full range of costs, including psychological and social, need to be considered.

	Discussion

The Crossroads 99 conference confirmed the overall usefulness of the original Wilson and Jungner framework. Given that it was developed well before modern testing for genetic susceptibility, its robustness is a testament to the foresight of the authors. Table 2 shows the hypothetical application of the Crossroads 99 framework to testing for susceptibility to colorectal cancer.^10-12 This illustrates which of the new criteria are not yet met and the usefulness of the new framework in identifying issues for further evaluation and research.

While the workshop primarily considered testing for genetic susceptibility to cancer, the new criteria should be valuable in the consideration of other genetic or susceptibility testing. For example, screening for hereditary haemochromatosis has emerged as a controversial issue.¹³ Among the issues to be examined with this test are the criteria for selecting the target population; the natural course and burden of disease; the interventions that could be offered to those who are screened, particularly in young people; the psychological and social effects of being tested; and the balance of economic, psychological, and social effects. System issues are paramount: screening programmes should be efficient, accessible, of high quality, ensure consumer choice, and respect the fundamental principles of human rights.

We hope that this revised framework will facilitate debate and comment regarding the development of screening programmes based on testing for genetic susceptibility. Ultimately, criteria such as these will be the basis for evidence based policy decisions for genetic screening programmes. Such a framework can provide an organised approach to the institution of screening programmes for susceptibility to ensure that fundamental issues, such as adequacy of resources for informed consent, capacity for follow up interventions, and systems issues are examined. While the potential benefits of such programmes are huge, the risks are considerable, and indiscriminate use could overwhelm our health systems.

	Acknowledgments

The Crossroads 99 meeting was held in November, 1999, in Toronto, in memory of Kathryn Taylor, PhD, who conceived the idea, developed the proposals, and garnered the support for it.

Contributors: VG was chair and principal author. He planned the meeting, prepared background materials, drafted the manuscript, prepared revisions, and is overall guarantor for this paper. A D DePetrillo, Cancer Care Ontario, Canada, and Zeev Rosberger, McGill University, Canada, co-chaired the conference and assisted with planning of meeting and preparation of materials. Timothy A Caulfield, University of Alberta, Canada; Mary Jane Esplen, Samuel Lunenfeld Research Institute, Canada; E Richard Gold, University of Western Ontario, Canada; Joan Murphy, University of Toronto, Canada; Donna Stewart, University of Toronto, Canada; Anne Summers, North York General Hospital, Canada, were conference facilitators and led discussion groups at workshop. Brian Doan, Toronto-Sunnybrook Regional Cancer Centre, Canada; Deborah Hellman, University of Maryland, United States; Claudine Giguere; Pamela James, York University, Canada; Raluca Nedelcu, Princess Margaret Hospital, Canada, were the recorders and reporters. A list of other participants who took part in the workshop can be found on the BMJ's website. All members of the working group reviewed the submission draft of the manuscript and had an opportunity to provide comments.

	Footnotes

Funding: Crossroads 99 Symposium and Conference was supported by the Canadian Institute for Health Research, the Social Sciences and Humanities Research Council, the National Cancer Institute of Canada with funds raised by the Canadian Cancer Society, the US National Cancer Institute, and the University of Toronto Interdepartmental division of oncology.

Competing interests: None declared.

Details of the workshop participants can be found on the BMJ's website

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(Accepted 14 February 2001)