FDA Issues Clinical Trials Guidance for Industry – and Upbraiding from Gottlieb

Following a raft of new proposals designed to expand eligibility for cancer clinical trials, the Food and Drug Administration has issued additional guidance that it said could support the development of precision medicines using clinical biomarkers. But it also came with a wag of the finger at the industry from outgoing Commissioner Scott Gottlieb.

The precision medicine guidance focused on three “enrichment strategies” designed to boost efficiency of drug development and support for precision medicine. These included decreasing variability through strategies like choosing patients with baseline measurements of a disease or biomarker; prognostic enrichment, through things like choosing patients with a greater likelihood of experiencing an event – e.g. disease progression or death – related to the trial’s endpoint; and predictive enrichment, such as choosing patients more likely to respond to treatment. Another guidance dealt with risk-based monitoring that incorporates more computerized models for clinical trial oversight, as opposed to traditional on-site trial monitoring.

But that came with scolding of the drug and contract research organization industries. “Unfortunately, we’ve seen continued reluctance to adopt innovative approaches among sponsors and clinical research organizations,” Gottlieb’s statement read. “In some cases, the business model adopted by the clinical trial establishment just isn’t compatible with the kind of positive but disruptive changes that certain innovations can enable. We appreciate that scientific and technical complexity is a real and ongoing challenge, but industry and academia also need to invest in and leverage these approaches and develop new incentives that reward collaboration and data sharing across the clinical research enterprise.”

Gottlieb resigned as FDA commissioner earlier this month. National Cancer Institute Director Norman Sharpless will step in as acting commissioner after Gottlieb’s departure. Earlier last week, the FDA had recommended that clinical trials in oncology let in more patients with HIV and hepatitis B and C.

The guidance, announced Friday in the Federal Register and posted to the FDA’s website, was a finalization of draft guidance issued previously. But notwithstanding Gottlieb’s criticism, the industry has begun to embrace more biomarker-driven, precision medicine-based approaches.

In 2017, the agency gave its first-ever approval to a drug for a biomarker-driven indication, when it approved Merck & Co.’s Keytruda (pembrolizumab) for any solid tumor with high levels of microsatellite instability or mismatch repair deficiency, also known respectively as MSI-H and dMMR. And in November 2018, it approved Loxo Oncology’s Vitrakvi (larotrectinib) for solid tumor cancers with NTRK fusions, regardless of where they occur in the body.

“The advent of precision medicine is challenging the entire medical research ecosystem to develop more efficient approaches to testing and developing diagnostics and therapeutics, to harness the full potential of science to reduce the suffering, death and disability caused by complex human illnesses,” Gottlieb’s statement read. “The agency is committed to developing a regulatory framework for precision medicine that generates robust evidence of product safety and efficacy as efficiently as possible, including frameworks that are more carefully suited to the kinds of precision technologies that underpin new treatments.”