FDA Announces Modernization Strategies for Clinical Trials of Precision Medicines

Former FDA Commissioner Scott Gottlieb says modernizing clinical trials is an agency priority.


With more diseases being redefined based on genomic subtype, new diseases targets are being identified that allow for the development of highly targeted precision medicines that can minimize — and in some cases repair — the genetic/biologic causes of diseases. Often, these medicines show efficacy in early clinical trials with few participants that, according to the U.S. Food and Drug Administration (FDA), can be used to allow earlier regulatory assessment of benefit and risk. Earlier approvals provide patients with earlier access to these novel therapies.


The FDA is, according to a statement by soon to be former Commissioner Scott Gottlieb, “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.”


To do so, the current approach to clinical trials must be modernized and streamlined, and disruptive technologies that make clinical research more effective must be adopted. “Without a more agile clinical research enterprise capable of testing more therapies or combinations of therapies against an expanding array of targets more efficiently and at lower total cost, important therapeutic opportunities may be delayed or discarded because we can’t afford to run trials needed to validate them,” according to Gottlieb’s statement.


To date, the FDA has introduced master protocol trial designs that can evaluate, in parallel, different drugs compared to their respective controls or to a single common control, but there is reluctance to adopt such innovative approaches by trial sponsors and clinical research organizations (CROs).


The FDA believes new research paradigms are needed to break down barriers between real world and clinical data, in order to allow trials to incorporate data from electronic health records, adopt electronic informed consent, and enroll more patients in clinical trials closer to where they live and work.


The agency recently released guidances for the industry on strategies that can support the development of precision medicines and on risk-based monitoring that can be accomplished through the incorporation of more computerized systems for effective oversight. Both are intended to facilitate efficient development of novel innovations while also generating the robust evidence needed to better assess product safety and efficacy.


A third guidance on nonclinical development of pharmaceuticals for severely debilitating or life-threatening hematologic disorders is designed to streamline the development of pharmaceuticals used to treat patients with severely debilitating or life threatening hematological disorders other than cancer, while protecting patient safety and avoiding the unnecessary use of animals in the conduct of trials. 


The FDA encourages enrichment trials for treatments that are targeted at groups of patients based on clinical laboratory tests or genomic or proteomic factors. In a biomarker-selected population, these trials can make it easier to detect the effect of a drug in smaller or shorter studies.  The agency has issued a guidance on enrichment strategies for clinical trials to expand the use of these approaches and facilitate development of innovative enrichment strategies. 


The guidance on risk-based monitoring is intended to help provide more effective oversight of trials while still protecting human subjects and assuring data integrity. It includes recommendations for implementing risk-based monitoring of investigational studies of human drug and biological products, medical devices or drug and device combinations. 


Cynthia A. Challener, Ph.D.

Dr. Challener is an established industry editor and technical writing expert in the areas of chemistry and pharmaceuticals. She writes for various corporations and associations, as well as marketing agencies and research organizations, including That’s Nice and Nice Insight.