Do trials reduce uncertainty? Assessing impact through cumulative meta-analysis of neonatal RCTs

Objective:to assess the impact of the latest randomized controlled trial (rct) to each systematic review (sr) in cochrane neonatal reviews.study design:we selected meta-analyses reporting the typical point estimate of the risk ratio for the primary outcome of the latest study (n=130), mortality (n=128) and the mean difference for the primary outcome (n=44). we employed cumulative meta-analysis to determine the typical estimate after each trial was added, and then performed multivariable logistic regression to determine factors predictive of study impact.results:for the stated primary outcome, 18% of latest rcts failed to narrow the confidence interval (ci), and 55% failed to decrease the ci by ⩾20%. only 8% changed the typical estimate directionality, and 11% caused a change to or from significance. latest rcts did not change the typical estimate in 18% of cases, and only 41% changed the typical estimate by at least 10%. the ability to narrow the ci by >20% was negatively associated with the number of previously published rcts (odds ratio 0.707). similar results were found in analysis of typical estimates for the outcomes of mortality and mean difference.conclusion:across a broad range of clinical questions, the latest rct failed to substantially narrow the ci of the typical estimate, to move the effect estimate or to change its statistical significance in a majority of cases. investigators and grant peer review committees should consider prioritizing less-studied topics or requiring formal consideration of optimal information size based on extant evidence in power calculations.