Timing of futility analyses for ‘proof of concept’ trials

This is the authors' abstract. We don't add key points for this paper.

'Proof of concept' (PoC) trials often are carried out to determine if a treatment is biologically active or inactive. If the predictive probability of rejecting a null hypothesis of no treatment effect on completion of the trial calculated using information accumulated before trial completion is sufficiently low, then the trial could be terminated and resources redirected more productively. If the predictive probability is high, some time might be gained by proceeding with further steps in drug development without affecting the course of the PoC trial in any way. We describe how the interim evaluation timing affects the ability to reach a decision to stop or continue as a function of various assumptions about the true parameters and about the interim outcomes. An important practical finding is that there is no point to carrying out an evaluation before accumulating about 40 per cent of the planned observations. Consequently, if trial costs are mostly at startup or for recruitment of subjects for extended periods of observation, it is unlikely that much benefit will be realized by considering the possibility of early termination for futility except possibly for administrative efficiencies with respect to resource and staff allocation.