Protocols for meta-analysis of intervention safety seldom specified methods to deal with rare events

Meta-analyses of rare events often generate unstable results, and selective reporting of the results may mislead the health care decision. Developing a synthesis plan for rare events in protocol may help to formulate the reporting. We aim to investigate whether existing protocols specified methods to deal with rare events.

Protocols (not including Cochrane protocols) for systematic reviews of health care interventions focused on the safety registered in PROSPERO were included. The proportion of protocols that specified methods to deal with rare events and the detailed methods were summarized. We compared the difference of proportions (PD) across different settings.

We identified 1,004 eligible protocols, of which, 119 (11.85%, 95% confidence interval (CI): 9.92%, 14.01%) specified methods to deal with rare events. The three most commonly planned methods were the Mantel-Haenszel, Peto's odds ratio, and continuity correction. Protocols planned a quantitative analysis (PD = 0.07, 95% CI: 0.02, 0.12; P = 0.004) and listed safety as a primary outcome (PD = 0.07, 95% CI: 0.01, 0.12; P = 0.018) were more likely to specify methods to deal with rare events.

Protocols for systematic reviews of intervention safety seldom specified methods to deal with rare events. Future systematic reviewers should provide a detailed and rigorous synthesis plan for rare events in their protocols.