Genetic Test Evaluation Framework to Aid Clinical Usefulness of Testing

Anew report by the National Academies of Sciences, Engineering, and Medicine provides a new decision framework for the use of genetic tests in clinical care. An Evidence Framework for Genetic Testing provides a seven- step process including defining the genetic testing scenario and a triage process for an expedited provisional decision, as well as a process for evidence review for tests needing further evaluation.

"There are challenges to evidence-based decision making around the use of genetic tests, including the paucity of the types of research studies on which evidence-based medical decisions depend, which are exacerbated by the accelerated development of new tests, variants, and technologic discoveries."

— Alfred O. Berg, M.D.

The report, by the National Academies' Committee on the Evidence Base for Genetic Testing, came from a request by the Department of Defense (DoD) to create recommendations for decision-making regarding the use of genetic tests in clinical care. DoD's Office of Health Affairs, which is responsible for developing cost-effective, high-quality health benefit for 9.6 million active-duty uniformed service members, retirees, and their families through the Military Health System, recognized the challenges posed by dramatic growth of genetic testing in the health care system, including the need for rigorous evaluation of not just their validity, but also their clinical utility and cost effectiveness, as well as the best ways to incorporate them into clinical practice.

"There are challenges to evidence-based decision making around the use of genetic tests, including the paucity of the types of research studies on which evidence-based medical decisions depend, which are exacerbated by the accelerated development of new tests, variants, and technologic discoveries," writes the committee, chaired by Alfred O. Berg, M.D., professor emeritus from the University of Washington, Seattle. "Randomized controlled trials to establish clinical utility are expensive and of long duration, so decisions about the clinical value of genetic testing are often based on lower levels of evidence. Policy making is often hampered by the lack of objective methods for setting decision thresholds."

While the committee's development of the framework intended to address general principles of clinical usefulness relevant to any genetic technology, it focused on germline DNA-based tests, including diagnostic genetic testing; predictive genetic testing (e.g., hereditary cancer, pharmacogenetic testing, newborn screening); and reproductive genetic testing (e.g., carrier, prenatal, and preimplantation testing).

The National Academies' committee recognized the "numerous" existing efforts to assess genetic tests by ad hoc groups, regulatory agencies, organizations, and professional societies. As such, they adapted existing frameworks to create a hybrid decision framework consisting of seven components to guide an evaluator through evidence-based decision-making. The steps include:

• Defining the genetic test scenario (e.g., population, clinical purpose, desired outcome, alternative methods);

• Triage whether the test should be covered, denied, or subject to additional evaluation – Is the test worthwhile? Is there evidentiary support for the test? What are the contextual factors (costs, ethical, legal, and social implications);

• Conduct evidence-based systematic reviews, if necessary;

• Reach a decision regarding whether or not to support the use of a genetic test;

• Track decisions and supporting information in a repository;

• Regularly review and revise decisions;

• Identify evidence gaps.

In addition to developing the framework, the National Academies committee recommends that the DoD advance the evidence base on genetic testing through independent and collaborative research. For instance, the National Academies suggests the DoD could undertake or support prospective studies of clinical utility or the DoD could implement processes for data collection and analysis of its own experience with genetic testing. Contributions of the large DoD TRICARE population to data repositories (e.g., ClinVar) could "substantially" advance the evidence base on clinical validity of genomic tests.

Takeaway: The National Academies' new decision framework for the use of genetic tests in clinical care may be widely applicable for evaluation of genetic tests. Additionally, the National Academies' encouragement may prompt DoD to substantially contribute to and grow the evidence base for genetic tests.