2.5 Trial Sequential Analysis

Trial sequential analysis (TSA) was performed to assess whether quantitative findings were robust and to calculate the required information size (RIS). As cumulative meta-analyses carry the risk of producing random errors due to sparse data and repetitive testing, we added TSA to the statistical methods. When the cumulative Z-curve crossed the monitoring boundary, the result was regarded as convincing. We used a two-sided trial sequential monitoring boundary and calculated the RIS based on α=0.05 and β=0.20. The mean differences and effect sizes were calculated from the included studies. The software TSA version 0.9.5.10 beta was used for this analysis (Copenhagen Trial Unit, Centre for Clinical Intervention Research, www.ctu.dk/tsa).