An alternative approach for estimating the number needed to treat for survival endpoints

To investigate the issues of the NNT based on the absolute risk reduction (ARR), namely NNT(ARR); and to propose an alternative definition and an estimation procedure based on the restricted mean survival time (RMST), namely NNT(RMST), for RCTs. Three recent clinical trials with survival endpoints, representing different scenarios, were selected to compare the performance of the NNT(ARR) and NNT(RMST). For each trial, both versions of NNT were estimated using the reconstructed individual-level data, and the average life gain (ALG) was derived to show the differences between the NNT(ARR) and NNT(RMST). Four hypothetical scenarios were constructed to further explore the advantages and disadvantages of each definition of the NNT for survival endpoints. For the illustrative trial examples, the NNT(ARR) failed to capture the profile of the treatment effect over time as it is calculated at a specific time point. Sometimes it may even result in misinterpretations of the treatment benefit. In particular, when either the observed event rates are low, the two survival curves cross, or a mixture of survival patterns exist. In contrast, the NNT(RMST) based on the average survival (or event-free) time can quantify the treatment effect more accurately and its interpretation is more intuitive and clinically meaningful. The NNT(RMST) can be used as an alternative measure for quantifying treatment effect in RCTs, especially so in the case of the ALG, which helps practitioners to better understand the magnitude of the benefit conferred by treatment.