Figure 4.

Trial sequential analysis (TSA) monitoring boundaries for strong evidence (the downward sloping line) after adding a ‘fake trial’ with 9000 patients.

Notes: The monitoring boundaries for moderate evidence (alpha =1%, beta =10%) were constructed using the Lan-DeMets alpha-spending approach corresponding to the O’Brien-Fleming boundaries, and were based on the information size required for moderate evidence (19,920 patients). The information size calculation was based on the assumption of a 5% incidence rate in the control group, and a 25% relative risk reduction. The cumulative Z-statistic crossed the monitoring boundaries for moderate evidence after adding a ‘fake trial’ with an intervention effect estimate of a 25% relative risk reduction, a 5% control group incidence rate and 9000 patients (4500 in each group). This result demonstrates that under the event rate assumptions made for the information size calculations, a new trial would need to include 9000 patients (4500 in each group) to make the meta-analysis conclusive with strong statistical support.