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Original research
Evidence of publication bias in multiple sclerosis clinical trials: a comparative analysis of published and unpublished studies registered in ClinicalTrials.gov
  1. Alejandro Rivero-de-Aguilar1,2,
  2. Mónica Pérez-Ríos1,3,
  3. Alberto Ruano-Raviña1,3,
  4. Cristina Candal-Pedreira1,3,
  5. Marilina Puente-Hernandez4,
  6. Joseph S Ross5,6,
  7. Leonor Varela-Lema1,3
  1. 1 Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela, Spain
  2. 2 Department of Neurology, University Hospital Complex of Pontevedra, Pontevedra, Spain
  3. 3 Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
  4. 4 Department of Neurology, Rio Hortega University Hospital, Valladolid, Spain
  5. 5 Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA
  6. 6 Department of Health Policy and Management, Yale University School of Public Health, New Haven, Connecticut, USA
  1. Correspondence to Professor Mónica Pérez-Ríos, Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela 15705, Spain; monica.perez.rios{at}usc.es

Abstract

Background Complete and timely publication of clinical trials ensures that patients and the medical community are fully informed when making treatment decisions. The aim of this study is to assess the publication of phase III and IV clinical trials on multiple sclerosis (MS) drugs that have been carried out between 2010 and 2019 and to identify the factors associated with their publication in peer-reviewed journals.

Methods An advanced search in ClinicalTrials.gov was performed and consecutive searches in PubMed, EMBASE and Google Scholar were conducted looking for the associated publications of all completed trials. Study design characteristics, results and other relevant information were extracted. Data was analysed following a case–control design. Clinical trials with associated publications in peer-reviewed journals were the cases and unpublished trials were the controls. A multivariate logistic regression analysis was performed to identify factors associated with trial publication.

Results One hundred and fifty clinical trials were included in the analysis. Ninety-six of them (64.0%) were published in peer-reviewed journals. In the multivariate analysis, factors associated with trial publication were a favourable primary outcome (OR 12.49, 95% CI 1.28 to 122.29) and reaching the originally estimated sample size (OR 41.97, 95% CI 1.96 to 900.48), while those associated with a lower odds of publication were having 20% or more patients lost to follow-up (OR 0.03, 95% CI 0.01 to 0.52) and evaluating drugs intended to improve treatment tolerability (OR 0.01, 95% CI 0.00 to 0.74).

Conclusions Phase III and IV clinical trials on MS drugs are prone to under-reporting and publication bias. Efforts must be made to promote a complete and accurate dissemination of data in MS clinical research.

  • multiple sclerosis
  • randomised trials

Data availability statement

Data are available upon reasonable request. Data is not public since it is being used for the PhD work of the first author. However, it is available upon reasonable request (contact: Mónica Pérez-Ríos, monica.perez.rios@usc.es).

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Data availability statement

Data are available upon reasonable request. Data is not public since it is being used for the PhD work of the first author. However, it is available upon reasonable request (contact: Mónica Pérez-Ríos, monica.perez.rios@usc.es).

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Footnotes

  • Contributors AR-d-A: methodology, data extraction, statistical analysis, interpretation of results, writing of the manuscript draft. MP-R: study conceptualisation, methodology, interpretation of results, revision and edition of the manuscript. AR-R: study conceptualisation, revision and edition of the manuscript. CC-P: methodology, revision and edition of the manuscript. MP-H: interpretation of results, revision and edition of the manuscript. JSR: interpretation of results, revision and edition of the manuscript. LV-L: study conceptualisation, methodology, statistical analysis, interpretation of results, revision and edition of the manuscript, supervision of the manuscript. AR-d-A is responsible for the overall content as guarantor.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.