State of the evidence: a survey of global disparities in clinical trials

Marshall, I. J.; L'Esperance, V.; Marshall, R.; Thomas, J.; Noel-Storr, A.; Soboczenski, F.; Nye, B.; Nenkova, A.; Wallace, B. C.

Introduction Ideally, 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. Methods We 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. Results We 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. Conclusion Research 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.