Clinical Studies Conducted Over The Total Product Life Cycle Of High-Risk Therapeutic Medical Devices Receiving Us Food And Drug Administration Premarket Approval In 2010 And 2011

The US Food and Drug Administration (FDA) approves high-risk medical devices, those that support or sustain human life or present potential unreasonable risk to patients, via the Premarket Approval (PMA) pathway. In recent years, the FDA has begun shifting premarket evidentiary requirements to the postmarket period as part of a broader effort to continually evaluate device safety and effectiveness throughout the total product life cycle. We therefore sought to characterize the clinical evidence generated for high-risk therapeutic devices over the total product life cycle. In October 2014, we identified all clinical studies of high-risk therapeutic devices receiving initial market approval via the PMA pathway in 2010 and 2011 through ClinicalTrials.gov and publicly available FDA documents. Studies were characterized by type (pivotal, studies that served as the basis of FDA approval; FDA-required postapproval studies [PAS]; or manufacturer/investigator-initiated); premarket or postmarket; status (completed, ongoing, or terminated/unknown); and design features, including enrollment, comparator, and longest duration of primary effectiveness end point follow-up. We identified 286 clinical studies of the 28 high-risk therapeutic devices which received initial marketing approval via the PMA pathway in 2010 and 2011: 82 (28.7%) premarket and 204 (71.3%) postmarket, among which there were 52 (18.2%) nonpivotal premarket studies, 30 (10.5%) pivotal premarket studies, 33 (11.5%) FDA-required PAS, and 171 (59.8%) manufacturer/investigator-initiated postmarket studies. Six of 33 (18.2%) PAS and 20 of 171 (11.7%) manufacturer/investigator-initiated postmarket studies were reported as completed. No postmarket studies were identified for 5 (17.9%) devices; 3 or fewer were identified for 13 (46.4%) devices overall. Median enrollment was 65 patients (interquartile range [IQR], 25-111), 241 patients (IQR, 147-415), 222 patients (IQR, 119-640), and 250 patients (IQR, 60-800) for nonpivotal premarket, pivotal, FDA-required PAS, and manufacturer/investigator-initiated postmarket studies, respectively. Approximately half of all studies used no comparator (pivotal: 13/30 [43.3%]; completed postmarket: 16/26 [61.5%]; ongoing postmarket: 70/153 [45.8%]). Median duration of primary effectiveness end point follow-up was 3.0 months (IQR, 3.0-12.0), 9.0 months (IQR, 0.3-12.0), and 12.0 months (IQR, 7.0-24.0) for pivotal, completed postmarket, and ongoing postmarket studies, respectively. In conclusion, among high-risk therapeutic devices approved via the FDA PMA pathway, total product life cycle evidence generation varied in both the number and quality of premarket and postmarket studies, with approximately 13% of initiated postmarket studies completed between 3 and 5 years after FDA approval