What is the clinical utility of genetic testing?

Evidence-based guidelines on the use of genetic tests in clinical practice require a systematic assessment of their usefulness, which, following a commonly used framework proposed in 1998 by a U.S. Task Force on Genetic Testing, is commonly referred to as clinical utility.Clinical utility in its narrowest sense refers to the ability of a screening or diagnostic test to prevent or ameliorate adverse health outcomes such as mortality, morbidity, or disability through the adoption of efficacious treatments conditioned on test results.2 A screening or diagnostic test alone does not have inherent utility; because it is the adoption of therapeutic or preventive interventions that influences health outcomes, the clinical utility of a test depends on effective access to appropriate interventions. This use is consistent with standard practice in evidence-based medicine, which focuses on objective measures of health status to evaluate interventions. Clinical utility can more broadly refer to any use of test results to inform clinical decision-making. Finally, in its broadest sense, clinical utility can refer to any outcomes considered important to individuals and families (e.g., reproductive decisions and psychosocial support). The field of genetic services, notably genetic counseling for Mendelian disorders, has emphasized the latter aspects of genetic testing.2 This commentary was prompted by a discussion at a workshop on the evaluation of genetic testing sponsored by the Centers for Disease Control and Prevention (CDC) in January 2005. The participants were a diverse group of experts in evidence-based medicine and genetics. The term “clinical utility” was familiar to many participants, and those who used the term were confident that they knew what it meant. However, there was no consensus as to what the term meant, with subgroups holding to different interpretations. This diversity of opinion led us to reflect on the meaning of the term and to review its previous uses. We came to realize that different definitions corresponded to different analytic and disciplinary or policy perspectives. We concur with Scheuner and Rotter3 that multiple perspectives should be considered in the evaluation of genetic testing, a conclusion that we had already reached. This commentary is a first response to their recent editorial. Only by making different perspectives explicit is it possible to reach agreement on the key endpoints to use in evaluating genetic testing for different audiences and purposes. Although different groups will not necessarily agree on which endpoints are most important, which involves value judgments and priorities, we hope that we can contribute to the clarification of these differences of opinion. The utility of genetic testing has different dimensions (public health, clinical, personal, and social), and the term “clinical utility” may be too limiting. In this commentary, we review the evolution of the concept of clinical utility of biochemical or molecular testing for genotypic variations associated with risk of disease. Potential health-related applications include screening, diagnostic, and carrier testing for single-gene disorders, testing of multiple loci to construct disease susceptibility risk profiles, and pharmacogenomic testing to predict drug–genome interactions. Most applications to date fall under the single-gene category, but more are expected for common diseases with complex genetic contributions and gene–environment interactions. We do not consider non–health-related uses of genotyping, such as testing for physical traits such as athletic ability.4