Strength of Study Evidence Examined by the FDA in Premarket Approval of Cardiovascular Devices

CONTEXT: Medical devices are common in clinical practice and have important effects on morbidity and mortality, yet there has not been a systematic examination of evidence used by the US Food and Drug Administration (FDA) for device approval. OBJECTIVES: To study premarket approval (PMA)--the most stringent FDA review process--of cardiovascular devices and to characterize the type and strength of evidence on which it is based. DATA SOURCES AND STUDY SELECTION: Systematic review of 78 summaries of safety and effectiveness data for 78 PMAs for high risk cardiovascular devices that received PMA between January 2000 and December 2007 corrected. DATA EXTRACTION: Examination of the methodological characteristics considered essential to minimize confounding and bias, as well as the primary end points of the 123 studies supporting the PMAs. RESULTS: Thirty-three of 123 studies (27%) used to support recent FDA approval of cardiovascular devices were randomized and 17 of 123 (14%) were blinded. Fifty-one of 78 PMAs (65%) were based on a single study. One hundred eleven of 213 primary end points (52%) were compared with controls and 34 of 111 controls (31%) were retrospective. One hundred eighty-seven of 213 primary end points (88%) were surrogate measures and 122 of 157 (78%) had a discrepancy between the number of patients enrolled in the study and the number analyzed. CONCLUSION: Premarket approval of cardiovascular devices by the FDA is often based on studies that lack adequate strength and may be prone to bias.