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Association between randomised trial evidence and global burden of disease: cross sectional study (Epidemiological Study of Randomized Trials—ESORT)

BMJ 2015; 350 doi: (Published 28 January 2015) Cite this as: BMJ 2015;350:h117
  1. Connor A Emdin, doctoral student1,
  2. Ayodele Odutayo, doctoral student23,
  3. Allan J Hsiao, masters student4,
  4. Mubeen Shakir, masters student4,
  5. Sally Hopewell, senior research fellow25,
  6. Kazem Rahimi, associate professor1,
  7. Douglas G Altman, director2
  1. 1George Institute for Global Health, University of Oxford, Oxford OX1 3DB, UK
  2. 2Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UKJ
  3. 3Faculty of Medicine, University of Toronto, Toronto, ON, Canada
  4. 4University of Oxford, Oxford, UK
  5. 5Centre d’Epidémiologie Clinique, Université Paris Descartes, INSERM U1153, France
  1. Correspondence to: C Emdin cemdin{at}
  • Accepted 6 December 2014


Objectives To determine whether an association exists between the number of published randomised controlled trials and the global burden of disease, whether certain diseases are under-investigated relative to their burden, and whether the relation between the output of randomised trials and global burden of disease can be explained by the relative disease burden in high and low income regions.

Design Cross sectional investigation.

Study sample All primary reports of randomised trials published in December 2012 and indexed in PubMed by 17 November 2013.

Main outcome measures Number of trials conducted and number of participants randomised for each of 239 different diseases or injuries; variation in each outcome explainable by total disability adjusted life years (a measure of the overall burden of each disease) and the ratio of disability adjusted life years in low income to high income regions (a measure of whether a disease is more likely to affect people living in high income regions) quantified using multivariable regression.

Results 4190 abstracts were reviewed and 1351 primary randomised trials identified, of which 1097 could be classified using the global burden of disease taxonomy. Total disability adjusted life years was poorly associated with number of randomised trials and number of participants randomised in univariable analysis (Spearman’s r=0.35 and 0.33, respectively), although it was a significant predictor in the univariable and multivariable models (P<0.001). Diseases for which the burden was predominantly located in low income regions had sevenfold fewer trials per million disability adjusted life years than diseases predominantly located in high income regions. However, only 26% of the variation in number of trials among diseases could be explained by total disability adjusted life years and the ratio of disability adjusted life years in low income regions to high income regions. Many high income type diseases (for example, neck pain, glomerulonephritis) have proportionally fewer randomised trials compared with low income type diseases (for example, vitamin A deficiency).

Conclusions Overall, a weak association existed between global burden of disease and number of published randomised trials. A global observatory for research is needed to monitor and reduce the discordance between the output of randomised trials and global burden of disease.


  • Contributors: CAE and AO contributed equally as first authors. CAE, AO, KR, SH, and DGA were involved in the design, implementation, and analysis of the study and in writing the final manuscript. AJH and MS were involved in the implementation of the study and in commenting on drafts of the final manuscript. CAE is the guarantor.

  • Funding: This study received no external funding. AO, CAE, AJH, and MS are funded by the Rhodes scholarship. KR is funded by the National Institute for Health Research (CDF-2013-06-012) and the NIHR Oxford BRC.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: Not needed.

  • Data sharing: Data and code are available on request from the lead author.

  • Transparency: The lead author (the manuscript’s guarantor) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

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