title: Premarket clinical evaluation of novel cardiovascular devices: quality analysis of premarket clinical studies submitted to the Food and Drug Administration 2000-2007.
abstract: The quality of clinical data submitted by manufacturers to support Food and Drug Administration cardiovascular device premarket approval (PMA) applications varies widely and formal quality assessment has not been previously performed. This study evaluated all original cardiovascular device PMAs with Food and Drug Administration decisions between January 1, 2000, and December 31, 2007, to assess the quality of clinical investigations submitted by manufacturers. Effectiveness and safety end points were judged high quality if they were clearly defined and associated with a specific time point for analysis. Subject accounting was high quality if 90% or greater of the original cohort was accounted for at study conclusion. In total, 88 cardiovascular device PMAs (77.3% permanent implants), 132 clinical studies, 37,328 study subjects (age 61.0 +/- 14.5 years, 33.9% women, 86.3% white), and 29,408 device recipients were analyzed. All PMAs contained clinical data. Primary effectiveness end points, primary safety end points, and subject accounting were deemed high quality in 81.8%, 60.2%, and 77.3% of pivotal studies, respectively. Key cardiovascular comorbidities (coronary artery disease 51.1%, diabetes 36.6%, hypertension 35.2%, heart failure 37.5%, tobacco use 31.8%) and race (14.8%) were infrequently reported, and studies rarely included patients younger than 18 years of age (10.2% of studies). Poorly defined safety and effectiveness end points, poor patient accounting, and incomplete collection of important patient comorbidities make device safety and effectiveness assessments more challenging. Women, pediatric, and nonwhite populations are underrepresented in premarket cardiovascular clinical trials. Manufacturers, regulators, and the clinical community should collaborate to address these study shortcomings to ensure that patients are treated with reliable, safe, and clinically useful medical devices.
authors.affiliation: Cardiovascular Institute, Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Kramer
authors.forename: Elias
authors.initials: E
authors.lastname: Mallis
authors.forename: Bram D
authors.initials: BD
authors.lastname: Zuckerman
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Zimmerman
authors.forename: William H
authors.initials: WH
authors.lastname: Maisel
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D015982:Bias; D002318:Cardiovascular Diseases / Q000628:therapy*; D002986:Clinical Trials as Topic / Q000379:methods / Q000592:standards*; D018795:Device Approval; D023381:Endpoint Determination; D004869:Equipment Safety; D004864:Equipment and Supplies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D014481:United States; D014486:United States Food and Drug Administration; D055815:Young Adult