But with the increase in genetic testing in homes and clinical settings comes challenges. What do physicians do with all of these data? How do clinicians evaluate the validity and clinical utility of genetic tests?
To tackle these questions and others, the National Academy of Medicine formed a committee to provide guidance. I recently spoke with one of the members, Sean David, MD, D.Phil, an associate professor of medicine at Stanford, about the committee's new recommendations and report.
What inspired you to participate in the NAM Committee on the Evidence for Genetic Testing?
The National Academy of Medicine consensus reports have high impact on national health policy and practice... so I jumped at the chance. In our work at Stanford, we struggle with advising patients on which genetic tests to recommend, which ones to order when requested by a patient and how to interpret results from the many direct-to-consumer genetic tests. We need guidance and a framework for making these decisions. The NAM committee addressed this challenge.
Years ago, I had a patient bring in a whole stack of direct-consumer whole genome sequencing results that showed her genetic risks for different illnesses. She asked me to interpret it for her, but there was far too much for me to consume during our brief office visit. And it was unclear what criteria to use when evaluating these tests. There’s been a rapid increase in the development of genetic tests with thousands of commercially available tests, but limited evidence regarding their validity for diagnosing disease and improving patient outcomes.
What was the committee’s mission?
Our charge was to examine the relevant medical and scientific literature to determine the evidence base for different types of genetic tests, as well as recommend a framework for decision-making regarding the use of genetic tests in clinical care.
This is the first consensus report on this topic. Although it was designed for the Military Health System, it should still be applicable to both military and civilian populations and may set benchmarks for private insurance companies. The report also encourages different agencies to cooperate and create a clinical data repository of evidence-based genetic testing decisions, which will be available to everyone. I think someone needs to do this to set the standard. Once that’s been done, at least we’ll have something we can all use as a benchmark.
How can this help guide clinical practice?
The decision framework can be used by physicians to determine which genetic tests are really ready for prime time in the clinic. For example, we know that if people are tested based on their family history and found to be at high risk for hereditary breast or ovarian cancer, they can have interventions that will improve their survival and outcomes. By using the decision framework, a physician can come up with a quick triage decision that it's a ‘yes’ test for someone with several family members with breast and/or ovarian cancer, and one that really all providers should know about.
Other genetic tests like tests for Alzheimer’s aren’t as clear. For instance, there could be a genetic test for a particular rare form of early onset Alzheimer’s associated with a particular mutation. If someone has that mutation, he may have a very high risk of early onset Alzheimer’s disease. Do we screen people for that? It will depend on the clinical testing scenario. If someone has family members who developed Alzheimer’s in their 40s, then it might be a good diagnostic test. Whereas, there might be another genetic test for associated risk of dementia where the causal relationship with Alzheimer’s may not be established. That’s an issue of clinical validity. So we might not offer that test routinely — to avoid giving patients information that might be misleading and might even cause some harm.
In addition, ethical, legal and social implications of genetic testing are important. For many patients — including parents of children with undiagnosed rare diseases — genetic testing may help end a diagnostic odyssey. Oftentimes geneticists will order whole genome testing without testing for something specific. There may be thousands or even millions of different genetic markers that are tested with the hope that they’ll find something that leads to a diagnosis. Evidence of clinical utility may be lacking in scenarios like these, but taking into account the value of tests to patients and their families is important — the context matters. There needs to be a certain amount of clinical judgment, and the committee isn't saying anything against this.
Previously: Genetic testing and its role in women’s health and cancer screening, Genetic counseling offers insights on testing for inherited heart conditions and Big Data in Biomedicine panelists: Genomics’ future is bright, thanks to data-science tools
Photo by National Human Genome Research Institute