- The Food and Drug Administration is stepping up its efforts to encourage wider adoption of new clinical trial methods, issuing new guidance documents Thursday intended to help drugmakers and clinical researchers design more efficient and less costly studies.
- Techniques like decentralized clinical testing or master protocol designs hold significant potential, FDA Commissioner Scott Gottlieb said in a statement, but haven’t been as broadly used as the regulatory would like.
- “Unfortunately we’ve seen continued reluctance to adopt innovative approaches among sponsors and clinical research organizations,” the outgoing agency chief said, while acknowledging that business incentives can limit the collaboration and data sharing that some of the FDA’s favored approaches entail.
Last November, Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, told an industry panel that she believed the current clinical trial system to be “broken.”
One of her proposed solutions was greater use of master protocols, a study design enabling researchers to test multiple treatments and disease types via a single trial.
Gottlieb appears to share a similar enthusiasm for the approach, noting the “infrastructure of these trials can last for decades” — reducing costs and shortening the time needed to stand up trial sites for each new drug candidate tested.
Convincing drugmakers to adopt such techniques broadly, however, can be difficult, particularly when companies are directly competing to develop therapies for a given disease.
“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,” Gottlieb noted.
Advances in precision medicine have made encouraging clinical innovation a more pressing priority for the FDA, though.
One guidance issued Thursday lays out strategies the FDA supports to “enrich” clinical trials with patients who are most likely to benefit. This can be seen most frequently in oncology, where individuals with specific genetic mutations can experience significant responses to treatments that are less effective for the general population.
Biomarker-defined studies — via PD-L1 expression levels in immunotherapy trials, for example — present opportunities for small, more cost-effective testing, the FDA argues.
It’s a view shared by National Cancer Institute Director Ned Sharpless, who this week was tapped by Health and Human Services Secretary Alex Azar to become interim FDA chief when Gottlieb departs next month.
“Modernizing the clinical trial infrastructure is a really important challenge for cancer research right now,” Sharpless told BioPharma Dive in an interview last December.
Rethinking how clinical trials are designed isn’t without concerns, however. Greater use of smaller or single-arm studies can speed drugs to patients in need of treatment, but can also result in approvals for drugs later shown to be less effective than first thought.
Most recently, for example, a confirmatory study of Merck & Co.’s Keytruda (pembrolizumab) in liver cancer failed to show a survival benefit just four months after the FDA had approved the drug based on findings from a smaller single-arm study.
The FDA also released guidance Thursday detailing how drugmakers can best use risk-based monitoring for clinical study and focus data verification efforts on those risks judged critical to a study’s quality.
