2:47 PM
Mar 14, 2019
 |  BC Extra  |  Politics & Policy

FDA guidances round out 'modernized' trial design framework

In line with outgoing FDA Commissioner Scott Gottlieb's push to modernize drug, biologic and device development, FDA released additional guidances Thursday to help sponsors design trials more efficiently, including a framework on targeted drug and biologic development. Gottlieb previewed the guidances in an interview with BioCentury last week (see "Gottlieb's Exit Interview").

"Modernizing clinical trials is an agency wide priority," Gottlieb said in a statement. "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."

In the first guidance, FDA broke down enrichment strategies to target enrollment in clinical trials to groups of patients more likely to reveal a treatment effect based on clinical laboratory tests, genomic or proteomic factors.

Enrichment can reduce the required size or duration of trials.

"The lower the prevalence of marker-positive patients in the unselected population and the smaller the treatment effect in the marker-negative population, the more the sample size can be reduced in a study of marker-positive patients compared to a study in an unselected population," FDA said in the guidance. For example, when the prevalence of marker-positive patients is 25% and no treatment effect is expected in the 75% of marker-negative patients, a trial that enrolled only marker-positive patients would require one-sixteenth the amount of patients than a trial in an unselected population.

The guidance also provided a framework on how to design adaptive enrichment trials, using I SPY-2 as an example, when there is incomplete information on the prevalence of a marker and/or the type and strength of the marker-outcome relationship.

A second guidance, published in a Q&A format, expands upon a 2013 guidance to help sponsors tailor risk-based monitoring plans for clinical trials based on the needs of the clinical investigation while focusing on those risks that have the greatest potential to adversely affect study quality, patient safety, and the collection and analysis of safety and efficacy endpoint data.

Gottlieb said that risk-based monitoring can be advanced using computerized algorithms that enable remote- and central trial monitoring, and through the development of advanced analytics to monitor data integrity as a trial is in process.

A third guidance published Thursday describes best practices for designing non-clinical studies, including in vitro and animal studies, to support the development of drugs to treat patients with severely debilitating or life threatening hematologic disorders, excluding cancer patients and the use of cell and gene therapies.

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