Characteristics of Clinical Studies Conducted Over the Total Product Life Cycle of High-Risk Therapeutic Medical Devices Receiving FDA Premarket Approval in 2010 and 2011.
OBJECTIVE
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. The generation of clinical evidence to understand device safety and effectiveness is shifting from predominantly premarket to continual study throughout the total product life cycle.


OBJECTIVE
To characterize the clinical evidence generated for high-risk therapeutic devices over the total product life cycle.


METHODS
All clinical studies of high-risk therapeutic devices receiving initial market approval via the PMA pathway in 2010 and 2011 identified through ClinicalTrials.gov and publicly available FDA documents as of October 2014.


METHODS
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.


RESULTS
In 2010 and 2011, 28 high-risk therapeutic devices received initial marketing approval via the PMA pathway. We identified 286 clinical studies of these devices: 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.


CONCLUSIONS
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.
Yale University School of Medicine, New Haven, Connecticut2Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, Connecticut.
Vinay K
VK
Rathi
Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, Connecticut3Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut4Robert Wood Johnson Foundation Cli.
Harlan M
HM
Krumholz
University of Colorado Anschutz Medical Campus, Aurora7Colorado Cardiovascular Outcomes Research Consortium, Denver.
Frederick A
FA
Masoudi
Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, Connecticut4Robert Wood Johnson Foundation Clinical Scholars Program, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut5Department o.
Joseph S
JS
Ross
D002986:Clinical Trials as Topic; D018795:Device Approval; D004869:Equipment Safety; D004864:Equipment and Supplies / Q000009:adverse effects*; D006801:Humans; D007221:Industry; D011358:Product Surveillance, Postmarketing; D012107:Research Design; D012108:Research Personnel; D012306:Risk; D014481:United States; D014486:United States Food and Drug Administration