State of the evidence: a survey of global disparities in clinical trials
Authors: Marshall Iain J , L’Esperence Veline , Marshall Rachel , Thomas James , Noel-Storr Anna , Soboczenski Frank , Nye Benjamin , Nenkova Ani , Wallace Byron C 
Published: October 2020

ABSTRACTIntroductionIdeally, health conditions causing the greatest global disease burden should attract increased research attention. We conducted a comprehensive global study investigating the number of randomised controlled trials (RCTs) published on different health conditions, and how this compares with the global disease burden that they impose.MethodsWe use machine learning to monitor PubMed daily, and find and analyse RCT reports. We assessed RCTs investigating the leading causes of morbidity and mortality from the Global Burden of Disease study. Using regression models, we compared numbers of actual RCTs in different health conditions to numbers predicted from their global disease burden (Disability-Adjusted Life Years [DALYs]). We investigated whether RCT numbers differed for conditions disproportionately affecting countries with lower socio-economic development.ResultsWe estimate 463,000 articles describing RCTs (95% prediction interval 439,000–485,000) were published from 1990 to July 2020. RCTs recruited a median of 72 participants (interquartile range 32–195). 82% of RCTs were conducted by researchers in the top fifth of countries by socio-economic development. As DALYs increased for a particular health condition by 10%, the number of RCTs in the same year increased by 5% (3.2%–6.9%), but the association was weak (adjusted R2=0.13). Conditions disproportionately affecting countries with lower socio-economic development, including respiratory infections and tuberculosis (7 thousand RCTs below predicted) and enteric infections (10 thousand RCTs below predicted), appear relatively under-researched for their disease burden. Each 10% shift in DALYs towards countries with low and middle socio-economic development was associated with a 4% reduction in RCTs (3.7%–4.9%). These disparities have not changed substantially over time.ConclusionResearch priorities are not well optimized to reduce the global burden of disease. Most RCTs are produced by highly developed countries, and the health needs of these countries have been, on average, favoured.Key questionsWhat is already known?Prior studies have manually investigated the relationship between published research in different health conditions and the global burden of disease that they impose.However, these analyses have been mostly limited to estimates of research funding from national funders, or smaller scale analysis of older publication records.These studies have highlighted disparities in research relative to burden, but they are not sufficient to enable global targeting of research to optimise improvements in disease burden.What are the new findings?We automatically process all of PubMed, allowing us to conduct a continually updated, comprehensive analysis of published reports of RCTs, including the number of participants per RCT and the health conditions studied.We found that considerable disparities exist between the relative volume of evidence on some conditions and the global burden of disease that they impose, as calculated by the Global Burden of Disease study.Further, our analysis suggests that there exists a smaller amount of evidence for conditions that impose a comparatively large burden of disease in lower-income countries.What do the new findings imply?Looking at numbers of RCTs published, and the numbers of participants in these trials, it seems that research priorities are not optimized to reduce the global burden of disease, and that research for conditions affecting higher-income countries has, on average, been favoured.The findings from this study could help research funders to focus research investment in areas where the largest reductions in disease burden could be made.