Interpreting meta-analysis according to the adequacy of sample size. An example using isoniazid chemoprophylaxis for tuberculosis in purified protein derivative negative HIV-infected individuals

OBJECTIVE: To illustrate the utility of statistical monitoring boundaries in meta-analysis, and provide a framework in which meta-analysis can be interpreted according to the adequacy of sample size. To propose a simple method for determining how many patients need to be randomized in a future trial before a meta-analysis can be deemed conclusive. STUDY DESIGN AND SETTING: Prospective meta-analysis of randomized clinical trials (RCTs) that evaluated the effectiveness of isoniazid chemoprophylaxis versus placebo for preventing the incidence of tuberculosis disease among human immunodeficiency virus (HIV)-positive individuals testing purified protein derivative negative. Assessment of meta-analysis precision using trial sequential analysis (TSA) with LanDeMets monitoring boundaries. Sample size determination for a future trials to make the meta-analysis conclusive according to the thresholds set by the monitoring boundaries. RESULTS: The meta-analysis included nine trials comprising 2,911 trial participants and yielded a relative risk of 0.74 (95% CI, 0.53–1.04, P = 0.082, I(2) = 0%). To deem the meta-analysis conclusive according to the thresholds set by the monitoring boundaries, a future RCT would need to randomize 3,800 participants. CONCLUSION: Statistical monitoring boundaries provide a framework for interpreting meta-analysis according to the adequacy of sample size and project the required sample size for a future RCT to make a meta-analysis conclusive.