title: Trends in Heart Failure Clinical Trials From 2001-2012.
abstract: BACKGROUND
  A systematic assessment of the temporal trends in heart failure (HF) clinical trials is lacking.
  
  
  RESULTS
  A total of 154 phase II-IV HF trials including 162,725 patients published from 2001 to 2012 in 8 high-impact-factor journals were reviewed. The median number of participants and sites per trial were 367 (interquartile range [IQR] 133-1450) and 38 (5-101), respectively. Median enrollment duration was 2.2 (1.5-3.3) years. The majority of studies investigated treatment for chronic HF (82.5%) and investigated HF with reduced ejection fraction (EF) (71.4%), whereas 27 trials (17.5%) enrolled patients with mixed EF and 9 (5.8%) enrolled HF with preserved EF patients alone. Enrollment rates did not significantly change over time (median 0.49 patients site(-1) month(-1), IQR 0.34-0.98; P = .53). Trials meeting their primary end point decreased over time from 73.5% in 2001-2003 to 52.5% in 2010-2012 (P = .08) and were more often smaller and used nonmortality end points. Industry trials were larger with shorter enrollment duration, more concentrated in North America, and more likely to be positive. Trials conducted exclusively outside North America and Western Europe had the highest enrollment rates (median 1.95 patients site(-1) month(-1), IQR 1.34-4.11).
  
  
  CONCLUSIONS
  Contemporary HF clinical trials display slow enrollment rates and decreased rates of positive outcomes over time. Positive trials tended to be smaller size with a higher proportion of surrogate end points.
authors.affiliation: Cardiology Division, Emory University, Atlanta, Georgia.
authors.forename: Ayman
authors.initials: A
authors.lastname: Samman Tahhan
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Muthiah
authors.initials: M
authors.lastname: Vaduganathan
authors.affiliation: Cardiology Division, Emory University, Atlanta, Georgia.
authors.forename: Anita
authors.initials: A
authors.lastname: Kelkar
authors.affiliation: Cardiology Division, Emory University, Atlanta, Georgia.
authors.forename: Vasiliki V
authors.initials: VV
authors.lastname: Georgiopoulou
authors.affiliation: Cardiology Division, Emory University, Atlanta, Georgia.
authors.forename: Andreas P
authors.initials: AP
authors.lastname: Kalogeropoulos
authors.affiliation: Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Greene
authors.affiliation: Division of Cardiology, University of California Los Angeles, Los Angeles, California.
authors.forename: Gregg C
authors.initials: GC
authors.lastname: Fonarow
authors.affiliation: Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Mihai
authors.initials: M
authors.lastname: Gheorghiade
authors.affiliation: Division of Cardiology, Stony Brook University, Stony Brook, New York. Electronic address: javed.butler@stonybrookmedicine.edu.
authors.forename: Javed
authors.initials: J
authors.lastname: Butler
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods*; D023381:Endpoint Determination / Q000379:methods / Q000639:trends*; D006333:Heart Failure / Q000175:diagnosis / Q000453:epidemiology / Q000628:therapy*; D006801:Humans; D018579:Patient Selection
keywords: Clinical trials; heart failure; outcomes; temporal trends