Comparative rates of harms in randomized trials from more developed versus less developed countries may be different

We set up to evaluate the relative risk of harms in trials performed in less developed vs. more developed countries.

Meta-epidemiologic evaluation using the Cochrane Database of Systematic Reviews. We considered meta-analyses with at least one randomized clinical trial (RCT) in a less developed country and one RCT in a more developed country. We targeted severe adverse events (AEs), discontinuations due to AEs, any AE, organ system-specific AEs, individual AEs, and all discontinuations due to any reason. We estimated the relative odds ratio (ROR) of harms between more and less developed countries for each topic and the summary ROR (sROR) across topics under each category of harms.

We identified 42 systematic reviews (128 meta-analyses, 521 independent RCTs). Summary sRORs did not differ significantly from 1.00 for any harm category. Nominally significant RORs were found in only 6/128 meta-analyses. However, in 27% (35/128) of meta-analyses the ROR point estimates indicated relative differences between country settings >2-fold. Considering also ROR 95% confidence intervals, in 92% (118/128) of meta-analyses one could not exclude a 2-fold difference in both directions.

We identified limited comparative evidence on harms in trials from these two country settings. Substantial differences in the risk point estimates were common; the potential for modest differences could rarely be excluded with confidence.