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General medicine
Association of study design features and treatment effects in trials of chronic medical conditions: a meta-epidemiological study
  1. Zhen Wang1,2,
  2. Fares Alahdab2,
  3. Magdoleen Farah2,
  4. Mohamed Seisa2,
  5. Mohammed Firwana2,
  6. Rami Rajjoub2,
  7. Samer Saadi2,
  8. Tabinda Jawaid2,
  9. Tarek Nayfeh2,
  10. Mohammad Hassan Murad1,2,3
  1. 1The Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
  2. 2Mayo Clinic Evidence-based Practice Center, Rochester, MN, USA
  3. 3Preventive Medicine, Mayo Clinic, Rochester, Minnesota, USA
  1. Correspondence to Zhen Wang, Health Care Policy and Research, Mayo Clinic Minnesota, Rochester, MN 55905, USA; Wang.Zhen{at}mayo.edu

Abstract

Objectives To evaluate the association of study design features and treatment effects in randomised controlled trials (RCTs) evaluating therapies for individuals with chronic medical conditions.

Design Meta-epidemiological study.

Setting RCTs from meta-analyses published in the 10 general medical journals with the highest impact factor published between 1 January 2007 and 10 June 2019 and evaluated a drug, procedure or device treatment of chronic medical conditions.

Main outcome measures The association between trial design features and the effect size, reporting a ratio of ORs (ROR) and 95% confidence interval (CI).

Results We included 1098 trials from 86 meta-analyses. The most common outcome in the trials was mortality (52%), followed by disease progression (16%) and adverse events (12%). Lack of blinding of patients and study personnel was associated with a larger treatment effect (ROR 1.12; 95% CI 1.00 to 1.25). There was no statistically significant association with random sequence generation, allocation concealment, blinding of outcome assessors, incomplete outcome data, whether trials were stopped early, study funding, type of interventions or with type of outcomes (objective vs subjective).

Conclusion The meta-epidemiological study did not demonstrate a clear pattern of association between risk of bias indicators and treatment effects in RCTs in chronic medical conditions. The unpredictability of the direction of bias emphasises the need to make every attempt to adhere to blinding, allocation concealment and reduce attrition bias.

Trial registration number Not applicable.

  • methods
  • internal medicine

Data availability statement

Data are available upon reasonable request.

Statistics from Altmetric.com

Data availability statement

Data are available upon reasonable request.

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Footnotes

  • Contributors ZW and MHM initiated the study and wrote the first manuscript draft. FA, MF, MS, MF, RR, SS, TJ and TN retrieved data from eligible studies. All authors read, commented on and approved the final manuscript.

  • 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.

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