FDA Guidance Document Addresses Design Considerations for Pivotal Clinical Studies

November 7, 2013—The US Food and Drug Administration (FDA) has issued a guidance document on design considerations for pivotal clinical investigations for medical devices. The guidance is for industry, clinical investigators, and FDA staff; specifically, it is intended to provide guidance both for those involved in designing clinical studies that are intended to support premarket submissions for medical devices and those FDA staff who review those submissions.

As noted in the document, the agency has articulated policies related to design of studies intended to support specific device types and a general policy of tailoring the evidentiary burden to the regulatory requirement; however, the agency has not attempted to describe the different clinical study designs that may be appropriate to support a device premarket submission or to define how a sponsor should decide which pivotal clinical study design should be used to support a submission for a particular device.

Among its goals, the guidance document:

• Describes different study design principles relevant to the development of medical device clinical studies that can be used to fulfill premarket clinical data requirements. It is not intended to provide a comprehensive tutorial on the best clinical and statistical practices for investigational medical device studies, advised the FDA.

• Provides information on design issues related to pivotal clinical investigations and does not address the other stages in any detail. Two broad types of clinical studies are distinguished in the document: clinical outcome studies and diagnostic clinical performance studies.

• Outlines principles for the design of premarket clinical studies that are pivotal in establishing the safety and effectiveness of a medical device. Practical issues and pitfalls in pivotal clinical study design are discussed, along with their effects on the conclusions that can be drawn from the studies concerning safety and effectiveness. The principles discussed in this guidance are intended to assist sponsors of marketing applications and investigators in designing studies adequate to provide a reasonable assurance of safety and effectiveness concerning a device.

• Provides recommendations to sponsors on how to design clinical investigations to support a PMA. However, sponsors who conduct clinical studies to support premarket notification for 510(k) marketing clearance and de novo submissions may also rely on the principles in this guidance document.

Device developers can gain insight about important pivotal study design issues for devices in each of these categories. At the same time, communication with FDA review staff (eg, through a presubmission interaction) is often valuable in arriving at pivotal clinical study designs that are both practical and adequate, noted the FDA guidance.