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Prevalence, Characteristics, and Publication of Discontinued Randomized Trials

2014; American Medical Association; Volume: 311; Issue: 10 Linguagem: Inglês

10.1001/jama.2014.1361

1538-3598

Benjamin Kasenda, Erik von Elm, John J. You, Anette Blümle, Yuki Tomonaga, Ramon Saccilotto, Alain Amstutz, Theresa Bengough, Joerg J Meerpohl, Mihaela Stegert, Kari A.O. Tikkinen, Ignacio Neumann, Alonso Carrasco–Labra, Markus Faulhaber, Sohail Mulla, Dominik Mertz, Elie A. Akl, Dirk Bassler, Jason W. Busse, Ignacio Ferreira‐González, François Lamontagne, Alain Nordmann, Viktoria Gloy, Heike Raatz, Lorenzo Moja, Rachel Rosenthal, Shanil Ebrahim, Stefan Schandelmaier, Xin Sun, Per Olav Vandvik, Bradley C. Johnston, Martin A. Walter, Bernard Burnand, Matthias Schwenkglenks, Lars G. Hemkens, Heiner C. Bucher, Gordon Guyatt, Matthias Briel,

Statistical Methods in Clinical Trials

Importance The discontinuation of randomized clinical trials (RCTs) raises ethical concerns and often wastes scarce research resources. The epidemiology of discontinued RCTs, however, remains unclear. Objectives To determine the prevalence, characteristics, and publication history of discontinued RCTs and to investigate factors associated with RCT discontinuation due to poor recruitment and with nonpublication. Design and Setting Retrospective cohort of RCTs based on archived protocols approved by 6 research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We recorded trial characteristics and planned recruitment from included protocols. Last follow-up of RCTs was April 27, 2013. Main Outcomes and Measures Completion status, reported reasons for discontinuation, and publication status of RCTs as determined by correspondence with the research ethics committees, literature searches, and investigator surveys. Results After a median follow-up of 11.6 years (range, 8.8-12.6 years), 253 of 1017 included RCTs were discontinued (24.9% [95% CI, 22.3%-27.6%]). Only 96 of 253 discontinuations (37.9% [95% CI, 32.0%-44.3%]) were reported to ethics committees. The most frequent reason for discontinuation was poor recruitment (101/1017; 9.9% [95% CI, 8.2%-12.0%]). In multivariable analysis, industry sponsorship vs investigator sponsorship (8.4% vs 26.5%; odds ratio [OR], 0.25 [95% CI, 0.15-0.43]; P < .001) and a larger planned sample size in increments of 100 (−0.7%; OR, 0.96 [95% CI, 0.92-1.00]; P = .04) were associated with lower rates of discontinuation due to poor recruitment. Discontinued trials were more likely to remain unpublished than completed trials (55.1% vs 33.6%; OR, 3.19 [95% CI, 2.29-4.43]; P < .001). Conclusions and Relevance In this sample of trials based on RCT protocols from 6 research ethics committees, discontinuation was common, with poor recruitment being the most frequently reported reason. Greater efforts are needed to ensure the reporting of trial discontinuation to research ethics committees and the publication of results of discontinued trials.