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. 2014 Jul 16:349:g4539.
doi: 10.1136/bmj.g4539.

Subgroup analyses in randomised controlled trials: cohort study on trial protocols and journal publications

Benjamin Kasenda, Stefan Schandelmaier, Xin Sun, Erik von Elm, John You, Anette Blümle, Yuki Tomonaga, Ramon Saccilotto, Alain Amstutz, Theresa Bengough, Joerg J Meerpohl, Mihaela Stegert, Kelechi K Olu, 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-González, Francois Lamontagne, Alain Nordmann, Viktoria Gloy, Heike Raatz, Lorenzo Moja, Rachel Rosenthal, Shanil Ebrahim, Per O Vandvik, Bradley C Johnston, Martin A Walter, Bernard Burnand, Matthias Schwenkglenks, Lars G Hemkens, Heiner C Bucher, Gordon H Guyatt, Matthias Briel; DISCO Study Group
Collaborators

Subgroup analyses in randomised controlled trials: cohort study on trial protocols and journal publications

Benjamin Kasenda et al. BMJ. .

Erratum in

  • BMJ. 2014;349:4921. Kasenda, Benjamin [added]; Schandelmaier, Stefan [added]; Sun, Xin [added]; von Elm, Erik [added]; You, John [added]; Blümle, Anette [added]; Tomonaga, Yuki (8) Saccilotto, Ramon (9) Amstutz, Alain [added]; Bengough, Theresa [added]; etc.

Abstract

Objective: To investigate the planning of subgroup analyses in protocols of randomised controlled trials and the agreement with corresponding full journal publications.

Design: Cohort of protocols of randomised controlled trial and subsequent full journal publications.

Setting: Six research ethics committees in Switzerland, Germany, and Canada.

Data sources: 894 protocols of randomised controlled trial involving patients approved by participating research ethics committees between 2000 and 2003 and 515 subsequent full journal publications.

Results: Of 894 protocols of randomised controlled trials, 252 (28.2%) included one or more planned subgroup analyses. Of those, 17 (6.7%) provided a clear hypothesis for at least one subgroup analysis, 10 (4.0%) anticipated the direction of a subgroup effect, and 87 (34.5%) planned a statistical test for interaction. Industry sponsored trials more often planned subgroup analyses compared with investigator sponsored trials (195/551 (35.4%) v 57/343 (16.6%), P<0.001). Of 515 identified journal publications, 246 (47.8%) reported at least one subgroup analysis. In 81 (32.9%) of the 246 publications reporting subgroup analyses, authors stated that subgroup analyses were prespecified, but this was not supported by 28 (34.6%) corresponding protocols. In 86 publications, authors claimed a subgroup effect, but only 36 (41.9%) corresponding protocols reported a planned subgroup analysis.

Conclusions: Subgroup analyses are insufficiently described in the protocols of randomised controlled trials submitted to research ethics committees, and investigators rarely specify the anticipated direction of subgroup effects. More than one third of statements in publications of randomised controlled trials about subgroup prespecification had no documentation in the corresponding protocols. Definitive judgments regarding credibility of claimed subgroup effects are not possible without access to protocols and analysis plans of randomised controlled trials.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: study funding by the Swiss National Science Foundation (grant 320030_133540/1) and the German Research Foundation (grant EL 544/1-2), no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, and no other relationships or activities that could appear to have influenced the submitted work.

Figures

None
Study flow of protocols of randomised controlled trials and publications. *Only protocols from two subsidiary research ethics committees responsible for paediatric and surgical randomised controlled trials were screened. †No results from randomised comparison published
See this image and copyright information in PMC

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