Defining purpose: a key step in genetic test evaluation

Abstract

The introduction of new genetic tests, like other medical innovations, can be conceptualized as a three-step process. Tests are proposed for use based on research findings and clinical reasoning; an evaluation occurs; and judgments are made about clinical use and reimbursement (Fig. 1). The evaluation may be informal, as when a clinician determines whether a new test will be helpful in a particular patient encounter, or formal, as when a practice guideline panel utilizes a defined methodology to assess a test or a health care funder utilizes a set of criteria to determine test coverage. Although genetic tests are often described in terms of technology, a full evaluation requires that the test be considered as a clinical process in which the laboratory assay, or other testing procedure, is done to acquire information about a particular health condition, in a defined population, for a specific clinical purpose.1 Genetic tests have a wide range of health care applications. They are used to confirm the presence of a genetic condition, identify reproductive risks, and select preventive therapy. Testing occurs in newborn screening programs and in primary, specialty, and prenatal care, and may be initiated on the basis of clinical symptoms, family history, or population demographics. Genetic tests also utilize a range of technologies, and vary considerably in their predictive value. This diversity poses a challenge for the evaluation process. Several groups have considered methods for genetic test evaluation,2–5 and model programs for systematic evaluation have been established in the United States (Evaluation of Genomic Applications in Practice and Prevention6) and the UK (the UK Genetic Testing Network7). To date, however, the evaluation process has not fully addressed the clinical diversity of genetic tests. The Evaluation of Genomic Applications in Practice and Prevention project has focused on genetic tests related to common disorders and drug therapy, whereas the United Kingdom Genetic Testing Network has primarily addressed tests for single gene disorders. An effort by the Secretary’s Advisory Committee on Genetic Testing to categorize genetic tests into those requiring higher versus lower levels of scrutiny was not successful.8 To address the challenge of genetic test diversity, we propose an outcome-orientated taxonomy for defining test purpose. A focus on health outcomes allows the definition of a small and informative set of purposes for genetic testing, despite the range of technologies and clinical settings in which testing occurs. Defining test purpose in turn clarifies the benefits to be expected from the testing process, and provides guidance to clinicians and policy makers concerning the evidence needed to support test use. Defining test purpose, therefore, is an important first step in genetic test evaluation.