Planning for complex and innovative trial designs often require extensive simulations in order to optimize the design parameters (sample size, no. and timing of interim looks, adaptive decision rules, futility and efficacy stopping rules, etc.) and to establish the operating characteristics (power, type-I error rate, etc.) of the design. Bayesian adaptive designs in general fall under simulated guided designs.
Even when design parameters and adjustment to account for adaptive changes in study design can be handled using closed form asymptotic expressions, for example for most designs incorporating a sample size re-estimation (SSR) at an interim look or a design incorporating group sequential boundaries for possible early efficacy stopping, simulations provide a deeper look into the nuts and bolts of the design and help in further optimization. These optimizations can minimize sample size and/or trial duration or minimize the probability of making incorrect interim decisions.
Simulations also help in aligning the trial design and objectives with respect to recruitment rates, lost-to-follow-up rates, disease prevalence or incidence rates as in a vaccine trial or a diagnostic device validation trial or prevalence of sub-populations in a study incorporating a stratified randomization.
For time to events trials, while most of the asymptotic theory is based on the assumption of constant (over time) and/or proportional hazards, simulation can used to gauge the sensivity of such assumptions under scenarios such as delayed treatment effect or non-proportional hazards in general can be studied and be accounted for in sample size and power consideration in order to mitigate such risks as that of an underpowered trial.
Our statistical team routinely works on complex adaptive and innovative trial designs and are well equipped with agile programming skills to rapidly set up simulations to be able to finalize study designs in a timely fashion. Simulation results for complex adaptive designs are routinely requested by the regulatory bodies and we provide these as part of a statistical planning document which also provides a detailed description of the design and design paramters. This document can then feed into the design details in the protocol, statistical analysis plans, data monitoring plans and charters, and other study documents.