Performance of different clinical trial designs to evaluate treatments during an epidemic.

In the 2013-2016 west Africa outbreak of Ebola Virus Disease (EVD), most of the planned clinical trials failed to reach a conclusion within the time frame of the epidemic. The performance of clinical trial designs for the evaluation of one or more experimental treatments in the specific context of an ongoing epidemic with changing case fatality rates (CFR) and unpredictable case numbers is unclear. We conduct a comprehensive evaluation of commonly used two- and multi-arm clinical trial designs based on real data, which was recorded during the 2013-16 EVD epidemic in west Africa.

Instrumental variable estimation in semi-parametric additive hazards models.

Instrumental variable methods allow unbiased estimation in the presence of unmeasured confounders when an appropriate instrumental variable is available. Two-stage least-squares and residual inclusion methods have recently been adapted to additive hazard models for censored survival data. The semi-parametric additive hazard model which can include time-independent and time-dependent covariate effects is particularly suited for the two-stage residual inclusion method, since it allows direct estimation of time-independent covariate effects without restricting the effect of the residual on the hazard.