On November 7, 2013, FDA published its final guidance document on Design Considerations for Pivotal Clinical Investigations for Medical Devices.  The 57-page guidance finalizes a draft guidance issued by the agency on August 15, 2011.  The guidance “is intended to provide guidance to those involved in designing clinical studies intended to support premarket submissions for medical devices and for FDA staff who review those submissions.”

Summary of Key Provisions

The guidance applies to both therapeutic and diagnostic devices and provides information on design issues for pivotal clinical trials, defined as “a definitive study in which evidence is gathered to support the safety and effectiveness evaluation of the medical device for its intended use.”  The guidance does not apply to either exploratory (e.g. pilot) studies, postmarket studies, or studies to support HDE applications.

The guidance provides general principles for the choice of study design, including types of studies, bias and variability in device performance, study objectives, subject selection, site selection, and comparative study designs.  The document distinguishes between two broad types of clinical studies:  clinical outcome studies and diagnostic clinical performance studies, providing factors to be considered for each type.

When FDA reviews pivotal clinical studies to determine whether they provide reasonable assurance of device safety and effectiveness, “FDA recognizes that there may be several types of studies that can fulfill this expectation.”  The agency therefore encourages applicants to meet with FDA to discuss study design choices prior to study commencement.


Commenters on the draft guidance expressed concern about FDA’s expectation for the type of studies needed to support submissions.  For example, Advamed stated “the overriding message throughout the draft guidance appears to be that randomized, blind, even double-blind trials, are always the preferred trial designs to support pre-market applications or 510(k) submissions requiring clinical studies.”  Although FDA notes in the final guidance that it is guided by the “least burdensome” provisions of the Food, Drug and Cosmetic Act, and “that the evidentiary burden must be commensurate with the appropriate regulatory and scientific requirements,” the final guidance retains a focus on randomized, controlled clinical studies.  This again raises the concern that FDA will increasingly require such studies to support marketing applications.