FDA and PGx Testing: What Gives?

Many healthcare professionals have been wondering what’s going on with the FDA and pharmacogenomic (PGx) testing. Within the past 19 months the FDA has approved direct-to-consumer PGx testing—but stated that the results of such tests must be confirmed by separate PGx tests ordered by a healthcare provider. What’s more, the agency has issued warning letters to PGx testing laboratories about reporting gene-drug relationships (GDRs) that don’t have sufficient clinical evidence, and has warned the public and healthcare professionals not to make medication changes based on testing not approved by the FDA.

Many PGx tests are laboratory-developed tests (LDTs) that have not been evaluated by the FDA and instead fall under CLIA (Clinical Laboratory Improvement Amendments). Even though some labs have worked closely with the FDA on these matters, some have finally decided to exclude, and others were told by the agency to exclude, medications from their results. This reporting change has made it particularly difficult for providers/pharmacists when interpreting data and making recommendations. In fact, many stakeholders have been affected by these “rules” that seem to have been inconsistently applied.

Unanswered Questions

Because of the many questions raised by the FDA’s actions, the Precision Medicine Coalition (PMC) invited Timothy Stenzel, MD, PhD, the Director of the FDA’s Office of In Vitro Diagnostics and Radiological Health of the Center for Devices and Radiological Health (CDRH), to speak about the issue. His talk, titled “Considering FDA’s Activity in Pharmacogenomics,” took place at the PMC’s Science and Public Policy Committees meeting on Tuesday, Dec. 10th.

I was very interested in hearing his talk to get answers to the many questions I and others have about the FDA’s recent PGx activity. However, his talk didn’t answer any of the questions or include anything specific about PGx. Instead, it consisted of information about the FDA’s concept of collaborative communities (CCs), which, according to the agency, are intended to be “continuing forums where public and private sector members proactively work together to achieve common objectives and outcomes, solve shared challenges, and leverage collective opportunities in an environment of trust, respect, empathy and openness.” There are criteria that need to be met in order to be a CC, including that all stakeholders should be included in it and should have an equal voice in decisions.

The FDA decides whether to become a CC member on a case-by-case basis, dependent on several criteria that may include a governance structure, a convener, a plan to measure success, and a mechanism for sustained engagement. Dr. Stenzel alluded to the fact that the FDA would probably not be a member of this CC unless all stakeholders were represented in it. (For more information about CCs, check out the webpage including the toolkit at https://www.fda.gov/about-fda/cdrh-strategic-priorities-and-updates/collaborative-communities-addressing-health-care-challenges-together.)

A question-and-answer session followed the short presentation. The questions were explicitly about PGx, the FDA’s actions, and what actions the FDA could or would take in the future. The answers, unfortunately, were nonspecific, added little substantive information, and left me with even more questions and confusion. The two significant statements that Dr. Stenzel made were that the FDA was going to do something “soon” and that PGx is a top priority in 2020. Uncertainty seems to be a repetitive theme with the FDA’s actions and PGx in recent months. When asked several direct questions, Dr. Stenzel’s  answer was to talk with him or the CDRH about specifics.

The FDA has not told labs which regulations they have violated nor the agency’s policy for how to correct problems so that drugs could be reported. The agency has also warned the labs not to inform providers of, or reference clinical guidelines for, GDRs widely accepted by the PGx community (such as those developed by the Clinical Pharmacogenetic Implementation Consortium).

So, is the problem even definite? Is it multifactorial? Is it with the evidence; with the science in PGx not being defined; with LDTs not being evaluated or regulated by the FDA; with reports being wrong; or with outdated FDA drug labeling? Or is the problem that all stakeholders don’t agree on what the problem is?

Trying to Move Forward

The Centers for Medicare & Medicaid Services has already been covering some PGx testing. UnitedHealthcare and SelectHealth (in a pilot program) will start paying for PGx panels designed to evaluate depression treatment this year. Clearly, these stakeholders think there’s enough clinical evidence.

In December, the PMC and the American Society of Pharmacovigilance (ASP) co-hosted a meeting to review a draft charter written by the ASP for a CC in pharmacogenomics called STRIPE: Standardizing Laboratory Practices in Pharmacogenomics. The meeting was open to the public and recorded. It can be viewed at http://www.stopadr.org/stripe.

Meanwhile, in communicating with the FDA, the Depression and Bipolar Support Alliance, Mental Health America, the National Alliance on Mental Illness, and the National Council for Behavioral Health together assert that excluding medications from PGx reports may cause harm for patients. The American Clinical Laboratory Association has written to the FDA challenging its authority to regulate LDTs. The FDA, however, insists that even though it has chosen not to regulate LDTs in the past, under the law, it has the authority to do so.

This month, a coalition of PGx testing labs, software companies that enable testing, and physicians that use PGx joined together to form the Coalition to Preserve Access to Pharmacogenomics (CPAP). The group has filed a citizen petition—a mechanism by which members of the public can request the FDA to change its policies—asking the FDA to stop its oversight limiting PGx services. Such petitions open a public docket where other interested parties can comment, creating a public record and increasing transparency. The FDA legally must respond to the petition at some point.

Jeff Gibbs, the director of the law firm that filed the petition, claims that the FDA's actions harm patient care and restrict the flow of PGx information to physicians, contrary to the agency's goals. He also stated that the FDA's actions violate the Administrative Procedure Act, raise First Amendment issues, and have caused much confusion for labs, PGx software providers, and physicians.

There are intentions to form a CC for pharmacogenomics, but the organization to lead the formation has not been chosen. Which stakeholder groups would be included and whether the discussions would be public is also unknown. If the FDA determines that not all stakeholders have been included, it may choose not to be a member. The CPAP, for its part, isn’t satisfied that the CC would address its concerns and is asking the FDA to convene a public hearing.

Since CCs don’t advise the FDA and aren’t managed by them, there is the real possibility that the CC could do a lot of work, but the FDA would not have to accept or even consider any of it. The processes which the CCs need to go through don’t allow for quick action, so these issues could continue for quite some time.

It’ll be interesting to see how all this unfolds and what the outcome(s) will be. Will there be a decrease in the use of PGx testing, possible non-optimal use of medications, and poorer patient outcomes than if medications were included on reports of PGx labs that have reasonable clinical evidence for the gene-drug relationships? I hope not. 

In the meantime, if you or a colleague need help with pharmacogenomic report interpretation and recommendations, consider consulting with the experts at Genome Medical, Inc.

Topics: blog, genetic-counseling, genetic-testing, PGx, pharmacogenomics

Latest Posts

Partner Support

Provide standard-of-care genetics to more patients through virtual, on-demand specialty care.


Individual Service

Interested in exploring your DNA? Our genetic experts can help you make the right decisions.