title: Trends in characteristics of cardiovascular clinical trials 2001-2012.
abstract: BACKGROUND
  Efficient conduct of clinical trials is essential for the timely generation of critical medical knowledge.
  
  
  METHODS
  We systematically assessed size, duration, enrollment rates, and geographic distribution of randomized cardiovascular trials published between 2001 and 2012 in the 8 highest-impact journals in general medicine and cardiology.
  
  
  RESULTS
  Of the 1,224 trials, 27.0% were conducted in North America, 36.5% in Western Europe, and 7.7% in other countries, and 28.8% were multiregional. Trials enrolled a median of 452 patients (interquartile range 167-1,530) in 20 sites (2-76). Median duration was 2.1 (1.3-3.3) years, with an estimated enrollment rate of 1.1 (0.5-3.5) patients/site per month. Between 2001-2003 and 2009-2012, the proportion of North American trials decreased from 34.5% to 25.7% (P = .006), whereas that of multiregional trials (from 26.0% to 30.3%; P = .046) and trials conducted in other countries (from 4.6% to 10.3%; P = .012) increased. Over time, trials involved more patients (from 400 to 500 [median]; P = .032) and sites (from 20 to 22; P = .049), multiregional trials involved more countries (from 12 to 18; P = .031), and enrollment rate declined from 1.2 to 0.9 patients/site per month (P = .017). The proportion of trials meeting their primary end point ("positive") decreased from 69% to 57% (P < .001). Trials with higher enrollment rates were more likely to be positive (odds ratio 1.20 per doubling, 95% CI 1.12-1.29), as were industry-sponsored compared with government-sponsored trials (odds ratio 2.62, 95% CI 1.67-4.12).
  
  
  CONCLUSIONS
  From 2001 to 2012, cardiovascular clinical trials have become larger, more global, and less likely to meet their primary end point. Enrollment rates have declined, requiring more sites and regions.
authors: Division of Cardiology, Stony Brook University, Stony Brook, NY. Electronic address: javed.butler@stonybrookmedicine.edu.
authors: Javed
authors: J
authors: Butler
authors: Emory Cardiovascular Clinical Research Institute, Emory University, Atlanta, GA.
authors: Ayman Samman
authors: AS
authors: Tahhan
authors: Emory Cardiovascular Clinical Research Institute, Emory University, Atlanta, GA.
authors: Vasiliki V
authors: VV
authors: Georgiopoulou
authors: Emory Cardiovascular Clinical Research Institute, Emory University, Atlanta, GA.
authors: Anita
authors: A
authors: Kelkar
authors: Emory Cardiovascular Clinical Research Institute, Emory University, Atlanta, GA.
authors: Michael
authors: M
authors: Lee
authors: Good Samaritan Hospital, University of Cincinnati, Cincinnati, OH.
authors: Bilal
authors: B
authors: Khan
authors: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC.
authors: Eric
authors: E
authors: Peterson
authors: University of California, Los Angeles, CA.
authors: Gregg C
authors: GC
authors: Fonarow
authors: Emory Cardiovascular Clinical Research Institute, Emory University, Atlanta, GA.
authors: Andreas P
authors: AP
authors: Kalogeropoulos
authors: Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL.
authors: Mihai
authors: M
authors: Gheorghiade
mesh_terms: D002309:Cardiology / Q000379:methods*; D002318:Cardiovascular Diseases / Q000628:therapy*; D002986:Clinical Trials as Topic / Q000639:trends*; D005060:Europe; D006801:Humans; D009656:North America; D010506:Periodicals as Topic; D012189:Retrospective Studies