FDA Offers Guidance on Adaptive Clinical Trials

FDA Headquarters

A new guidance from the U.S. Food and Drug Administration (FDA) offers the agency’s latest thinking on how industry should design, run, and handle data reporting when leveraging adaptive clinical trials. The final “Adaptive Designs for Clinical Trials of Drugs and Biologics” guidance is largely unchanged from its 2018 draft predecessor.

The guidance also advises sponsors on the types of information to submit to facilitate FDA evaluation of clinical trials with adaptive designs, including Bayesian adaptive and complex trials that rely on computer simulations for their design.

FDA defines “adaptive design” as a clinical trial design that allows for prospectively planned modifications to one or more aspects of the design based on accumulating data from subjects in the trial.”

“Adaptive designs can provide a variety of advantages over non-adaptive designs,” FDA notes in the guidance. “These advantages arise from the fundamental property of clinical trials with an adaptive design: they allow the trial to adjust to information that was not available when the trial began.”

For example, in some cases, an adaptive design can provide a greater chance to detect a true drug effect (i.e., greater statistical power) than a comparable non-adaptive design.

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There are many ways in which an adaptive design can provide ethical advantages over a non-adaptive design, FDA says; for example, the ability to stop a trial early if it becomes clear that it is unlikely to demonstrate effectiveness. This can reduce the number of patients exposed to the unnecessary risk of an ineffective investigational treatment, and allow subjects the opportunity to explore more promising therapeutic alternatives.

FDA also suggested an adaptive design may be considered more acceptable to stakeholders than a comparable non-adaptive design because of the added flexibility. For example, sponsors might be more willing to commit to a trial that allows planned design modifications based on accumulating information. Patients may be more willing to enroll in trials that use response-adaptive randomization, because these trials can increase the probability that subjects will be assigned to the more effective treatment.

Author: Michael Causey