Commercial funding and estimated intervention effects in randomized clinical trials: Systematic review of meta-epidemiological studies

Abstract

We investigated to which degree commercial funding is associated with estimated intervention effects in randomized trials. We included meta-epidemiological studies with published data on the association between commercial funding and results or conclusions of randomized trials. We searched five databases and other sources. We selected one result per meta-epidemiological study, preferably unadjusted ratio of odds ratios (ROR), for example, odds ratio(commercial funding)/odds ratio(noncommercial funding). We pooled RORs in random-effects meta-analyses (ROR <1 indicated exaggerated intervention effects in commercially funded trials), subgrouped (preplanned) by study aim: commercial funding per se versus risk of commercial funder influence. We included eight meta-epidemiological studies (264 meta-analyses, 2725 trials). The summary ROR was 0.95 (95% confidence interval 0.85–1.06). Subgroup analysis revealed a difference (p = 0.02) between studies of commercial funding per se, ROR 1.06 (0.95–1.17) and studies of risk of commercial funder influence, ROR 0.88 (0.79–0.97). In conclusion, we found no statistically significant association between commercial funding and estimated intervention effects when combining studies of commercial funding per se and studies of risk of commercial funder influence. A preplanned subgroup analysis indicated that trials with high risk of commercial funder influence exaggerated intervention effects by 12% (21%–3%), on average. Our results differ from previous theoretical considerations and findings from methodological studies and therefore call for confirmation. We suggest it is prudent to interpret results from commercially funded trials with caution, especially when there is a risk that the funder had direct influence on trial design, conduct, analysis, or reporting.