Pivotal clinical trials with patient-reported outcome measures in premarket approval applications for high-risk medical devices from 2005 to 2018: Review, examples, and regulatory considerations

Background: Patient-reported outcome (PRO) measures are key to reflecting the patient experience and patient perspective when developing new medical devices. The PRO measures used in pivotal clinical trials for investigational medical devices are miscellaneous and diversified. Methods: This article analyzes and presents the trend and distribution of the use of PRO measures in the pivotal clinical trials for high-risk medical devices regulated and approved by the United States Food and Drug Administration (FDA) from 2005 to 2018 through Premarket Approval (PMA). Results: As clinical endpoints in pivotal clinical trials, the use of PRO measures in FDA-approved PMA applications for high-risk Class III medical devices significantly increased from September 2005 to December 2018. The percentage of PRO use peaked at the years 2014 and 2015 and remains high till 2018. The most used PRO measure among these PMAs was the 36-Item Short Form Survey quality-of-life questionnaire. Three examples are further elaborated in this article to show how the pivotal clinical trials are designed and analyzed with PRO measures as their clinical endpoints for FDA-regulated high-risk medical devices. The article also reiterates regulatory perspectives and considerations from the FDA. Conclusion: The regulatory perspectives and considerations provided by the FDA on evaluating PRO instruments and design and analysis of pivotal clinical trials with PRO measures should be closely followed in the development process of new medical devices.