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FDA Guidance Promotes Adaptive Designs for Medical Device Trials

Reprinted from the Guide to Good Clinical Practice with permission of Thompson Publishing Group, 805 15th St., Washington, D.C. 20005; www.thompson.com. To learn more about the Guide to Good Clinical Practice, visit: www.firstclinical.com/gcpguide.
The FDA’s Centers for Devices and Radiological Health and Biologics Evaluation and Research released a draft guidance May 15 for sponsors and FDA staff on how to plan and implement adaptive designs for device clinical studies.“Adaptive designs, when properly implemented, can reduce resource requirements and/or increase the chance of study success,” the agency said in announcing the guidance, which the centers were careful to note is not in effect now.
The guidance addresses adaptive designs for medical device clinical trials and is applicable to premarket medical device submissions, including premarket approval applications, premarket notification (510(k)) submissions, de novo submissions (evaluation of automatic class III designation), humanitarian device exemption applications, and investigational device exemption submissions and “can be applied throughout the clinical development program of a medical device, from feasibility studies to pivotal clinical trials.” However, the guidance “does not apply to clinical studies of combination products or co-development of a pharmaceutical product with an unapproved diagnostic test,” although “the underlying principles may be applicable to such studies.”
Adaptive trial designs allow for prospectively planned modifications to trials based on accumulating study data. “In nearly all situations, in order to preserve the integrity and validity of a trial, modifications should be prospectively planned and described in the clinical trial protocol prior to initiation of the study. However, in some specific circumstances, study modifications after the trial begins can be scientifically valid if the trial design decision-makers have had no access to the outcome results by treatment.” The guidance noted the “knowledge of outcome results by coded treatment groups, even without divulging which treatment is investigational, can undermine scientific validity.”
The guidance cautioned that “there is a real danger that an unplanned modification to a study may weaken its scientific validity and therefore [it] may not be approved or endorsed by FDA. Sponsors should anticipate and plan for modifications based on a variety of possible scenarios that could occur during the course of the trial.”