Fig. 7: A priori scrutiny of the interim analysis plan to evaluate possible advantages and disadvantages of timed additional analyses during the trial.

A In the case of immunotherapy with a potent effect, in silico trials help develop a rationale for the timing of the interim analyses. In these simulations, while an interim analysis at 12 months might not add value to the trial, analyses after 16 and 18 months, respectively, have a probability of approximately 25% and 40% to lead to early stopping with a positive result. B Multiple interim analyses can reduce the probability of confirming the desired treatment effect in case of a weak immunotherapy effect. C In the absence of any treatment effect (a control scenario), the number of interim analyses does not heavily influence the trial outcome. Each trial simulation contains 1200 patients (randomization ratio 1:1) to ensure adequate power of the trial. Trials are analyzed with a proportions test (Pearson’s chi-squared test). Treatment effect (fold increase of the T cell killing rate): strong=12, weak=4, no effect=0 (see Methods). All simulations were performed using M1. Source data are provided as a Source Data file.