Prevalence, characteristics, and publication of discontinued randomized trials

Benjamin Kasenda, Erik Von Elm, John 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 M. Mulla, Dominik Mertz, Elie A. Akl, Dirk Bassler, Jason W. Busse, Ignacio Ferreira-GonzálezFrancois Lamontagne, Alain Nordmann, Viktoria Gloy, Heike Raatz, Lorenzo Moja, Rachel Rosenthal, Shanil Ebrahim, Stefan Schandelmaier, Sun Xin, Per O. Vandvik, Bradley C. Johnston, Martin A. Walter, Bernard Burnand, Matthias Schwenkglenks, Lars G. Hemkens, Heiner C. Bucher, Gordon H. Guyatt, Matthias Briel

Research output: Contribution to journalArticle

Abstract

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 Discontinued trials were more likely to remain unpublished than completed trials (55.1% vs 33.6%; OR, 3.19 [95%CI, 2.29-4.43]; P 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.

Original languageEnglish
Pages (from-to)1045-1051
Number of pages7
JournalJournal of the American Medical Association
Volume311
Issue number10
DOIs
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Medicine(all)

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    Kasenda, B., Von Elm, E., You, J., Blümle, A., Tomonaga, Y., Saccilotto, R., Amstutz, A., Bengough, T., Meerpohl, J. J., Stegert, M., Tikkinen, K. A. O., Neumann, I., Carrasco-Labra, A., Faulhaber, M., Mulla, S. M., Mertz, D., Akl, E. A., Bassler, D., Busse, J. W., ... Briel, M. (2014). Prevalence, characteristics, and publication of discontinued randomized trials. Journal of the American Medical Association, 311(10), 1045-1051. https://doi.org/10.1001/jama.2014.1361