Lack of evidence has been identified as a major impediment to the translation of genomic knowledge into beneficial medical interventions [49
]. However, the task of defining what is adequate evidence may, in fact, be at the heart of many disputes and will need to be considered in developing consensus on clinical utility.
Perhaps the first issue to be addressed is whether ‘clinical utility’ should be considered relevant only in health care settings. A test that provides information of interest to consumers but is not medically actionable, like the APOE 4 test, might have a poor claim on health care resources [71
], yet might still represent an appropriate consumer product. If so, consumer safety would become a central policy concern, with a need to define the potential harms of testing, the regulatory models for pre-market test review, and the standards for the marketing of products [43
]. As debates about personal genomics already demonstrate, defining the line between consumer products and health care tests will also be difficult.
For tests used in health care, evidence standards will need to be based on what physicians, patients, and health care funders find convincing in establishing a benefit. For example, will a genetic risk assessment that is believed to motivate a change in patient behavior, rather than changes in physician testing or prescribing regimens, be considered medically actionable and thus worthy of a claim on health care dollars? The threshold defined by clinicians in practice may or may not conform to the rigorous standards proposed by groups such as EGAPP [72
] – and patients may view the threshold differently than clinicians.
Some will argue that clinicians in practice are ill equipped to assess the clinical utility of new genetic tests. Most have important deficiencies in their knowledge of genetics and genetic tests [73
], and most medical students do not retain the genetics education they received [74
]. It would therefore be unrealistic to presume that most clinicians will be able to integrate new genetic tests into their practice based on their assessment of the evidence. Public health efforts to increase the development of practice guidelines in genetics are underway [72
]. There is a need for greater physician engagement in the development and use of guidelines and more systematic efforts to assess the large number of genetic tests likely to emerge from current research [77
], with appropriate stakeholder input.
The evidence needed to make a compelling case for testing will undoubtedly vary by both test characteristics and testing purpose [12
]. The clinical utility of tests to diagnose rare, highly penetrant conditions will generally be established by small-scale studies that confirm the gene-disease association. On the other hand, tests for genetic susceptibility, intended to be used in population-based screening, are unlikely to be convincing without rigorous assessment of testing outcomes.
Clarification of different stakeholders whose interests are at stake, and their preferences and values, will also be important. In some cases – such as the use of testing to inform medical treatment of symptomatic patients – little controversy will be expected, and a convergence of values can be predicted. However, in other arenas, such as medical testing used for actions outside the medical system (e.g. APOE testing to inform personal decisions such as purchase of long-term care insurance) or population screening for rare conditions with variable phenotype and severity, controversy is to be expected. Stakeholders for these decisions include not only clinicians, patients and health care funders, but also test developers, regulatory agencies and lawmakers. In these latter cases, endless debate without resolution can occur – and clarifying the values that are at stake and how different stakeholders prioritize them may be the only way to move discussion forward to a resolution.
An early challenge in approaching this task is to determine how different stakeholder views can be defined and shared. While there are good reasons to separate the processes of regulatory review, development of professional practice guidelines, and funding decisions – because they are based on different governance – more opportunities are needed to discuss the different values that may be brought to each of these decision-making activities. Perhaps more important, with increasing attention to patient-centered care [78
], there is a need to move beyond expert-driven processes, to identify ways for meaningful input from the consumers who are both the intended beneficiaries and ultimate funders of genomic innovation.