Javed Butler1, Ayman Samman Tahhan2, Vasiliki V Georgiopoulou2, Anita Kelkar2, Michael Lee2, Bilal Khan3, Eric Peterson4, Gregg C Fonarow5, Andreas P Kalogeropoulos2, Mihai Gheorghiade6. 1. Division of Cardiology, Stony Brook University, Stony Brook, NY. Electronic address: javed.butler@stonybrookmedicine.edu. 2. Emory Cardiovascular Clinical Research Institute, Emory University, Atlanta, GA. 3. Good Samaritan Hospital, University of Cincinnati, Cincinnati, OH. 4. Duke Clinical Research Institute, Duke University Medical Center, Durham, NC. 5. University of California, Los Angeles, CA. 6. Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL.
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.
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: Robert J Mentz; Adrian F Hernandez; Lisa G Berdan; Tyrus Rorick; Emily C O'Brien; Jenny C Ibarra; Lesley H Curtis; Eric D Peterson Journal: Circulation Date: 2016-03-01 Impact factor: 29.690
Authors: Muthiah Vaduganathan; Amulya Nagarur; Arman Qamar; Ravi B Patel; Ann Marie Navar; Eric D Peterson; Deepak L Bhatt; Gregg C Fonarow; Clyde W Yancy; Javed Butler Journal: Circulation Date: 2017-11-13 Impact factor: 29.690
Authors: Louis A Kerkhoff; Javed Butler; Anita A Kelkar; Supriya Shore; Candace D Speight; Louisa K Wall; Neal W Dickert Journal: J Am Heart Assoc Date: 2016-06-17 Impact factor: 5.501
Authors: A Boswood; J Häggström; S G Gordon; G Wess; R L Stepien; M A Oyama; B W Keene; J Bonagura; K A MacDonald; M Patteson; S Smith; P R Fox; K Sanderson; R Woolley; V Szatmári; P Menaut; W M Church; M L O'Sullivan; J-P Jaudon; J-G Kresken; J Rush; K A Barrett; S L Rosenthal; A B Saunders; I Ljungvall; M Deinert; E Bomassi; A H Estrada; M J Fernandez Del Palacio; N S Moise; J A Abbott; Y Fujii; A Spier; M W Luethy; R A Santilli; M Uechi; A Tidholm; P Watson Journal: J Vet Intern Med Date: 2016-09-28 Impact factor: 3.333
Authors: Brendan Smyth; Konlawij Trongtrakul; Anna Haber; B Talbot; Carmel Hawley; Vlado Perkovic; Mark Woodward; Meg Jardine Journal: BMJ Glob Health Date: 2019-11-12