Anticipating Precision Medicine's Future

The science and technology to identify germline mutations and actionable mutations in cancers are “moving at a prodigious pace,” according to NIH Director Francis Collins, MD, PhD. Instead of investing in technologies that test a handful of genes at a time, researchers and regulators need to start planning for more routine whole-genome sequencing, said Collins, who spoke at a symposium sponsored by the American Association for Cancer Research and AdvaMedDx, “Transforming Cancer Care through Diagnostics and Personalized Medicine,” held in Washington, DC, on October 29.

Looking ahead 3 to 4 years, progress in cancer diagnosis “would be best achieved by utilizing a comprehensive look at the genome in a cancer and also the germline from an individual,” said Collins.

Last year, the NIH launched the Genetic Testing Registry, a free, online repository of information about different types of germline genetic tests, voluntarily submitted by test providers. Currently, the registry includes details such as the methodology and validity of more than 12,000 tests for 3,600 conditions, covering 2,400 genes.

In his keynote address about the promises and challenges of personalized medicine, also called precision medicine, Harold Varmus, MD, director of the National Cancer Institute, stressed the importance of accurate diagnostic testing to select the best treatment regimens. Doing so, he said, might not only improve patient outcomes but also save the health-care system money by avoiding the use of ineffective therapies. “The products of clinical investigation, if properly aggregated, stored, and analyzed, can lead to a growth in knowledge that drives further refinement of [cancer] taxonomic categories,” he said.

To chart a course forward in personalized medicine, the NIH is working closely with the U.S. Food and Drug Administration (FDA). The agency's efforts to advance regulatory standards, methods, and tools in support of personalized medicine are described in a report, “Paving the Way for Personalized Medicine: FDA's Role in a New Era of Medical Product Development,” which was released on the same day as the conference.

The coming changes in personalized medicine pose a clear challenge to the agency's regulatory framework, noted FDA commissioner Margaret Hamburg, MD. “We have to go from looking at very discrete diagnostic tests to a system or platform that will be looking at literally billions of base pairs and generating lots of information that bears on lots of conditions,” she said.

One challenge associated with obtaining all of that information, Collins added, is how to handle “incidental findings,” genetic test results that may have potential health consequences but have nothing to do with why the test was originally ordered. The clinical significance of genetic variants often isn't clear, for example, and specialists often disagree about whether to report incidental findings for conditions that have few effective treatments.

The goal, said Hamburg, is to provide both the health-care system and patients with some assurance that these tests are done in responsible ways, while offering meaningful information that has analytic and clinical validity for the condition being treated.