Referee report. For: Highly Efficient Clinical Trials Simulator (HECT): Software application for planning and simulating platform adaptive trials [version 2; peer review: 1 approved]

Robert A. Beckman, Valeriy Korostyshevskiy
Adaptive designs and platform designs are among two Background: common clinical trial innovations that are increasingly being used to manage medical intervention portfolios and attain faster regulatory approvals. Planning of adaptive and platform trials necessitate simulations to understand how a set of adaptation rules will likely affect the properties of the trial. Clinical trial simulations, however, remain a black box to many clinical trials researchers who are not statisticians. In this
more » ... icle we introduce a simple intuitive open-source Results: browser-based clinical trial simulator for planning adaptive and platform trials. The software application is implemented in and features a RShiny graphical user interface that allows the user to set key clinical trial parameters and explore multiple scenarios such as varying treatment effects, control response and adherence, as well as number of interim looks and adaptation rules. The software provides simulation options for a number of designs such as dropping treatment arms for futility, adding a new treatment arm (i.e., platform design), and stopping a trial early based on superiority. All available adaptations are based on underlying Bayesian probabilities. The software comes with a number of graphical outputs to examine properties of individual simulated trials. The main output is a comparison of trial design performance across several simulations, graphically summarizing type I error (false positive risk), power, and expected cost/time to completion of the considered designs. We have developed and validated an intuitive highly efficient Conclusion: clinical trial simulator for planning of clinical trials. The software is open-source and caters to clinical trial investigators who do not have the statistical capacity for trial simulations available in their team. The software can be accessed via any web browser via the following link: PubMed Abstract | Publisher Full Text 2. Hatfield I, Allison A, Flight L, et al.: Adaptive designs undertaken in clinical research: a review of registered clinical trials. Trials. 2016; 17(1): 150. PubMed Abstract | Publisher Full Text | Free Full Text 3. Saville BR, Berry SM: Efficiencies of platform clinical trials: A vision of the future. Clin Trials. 2016; 13(3): 358-366. PubMed Abstract | Publisher Full Text 4. Thorlund K, Haggstrom J, Park JJ, et al.: Key design considerations for adaptive clinical trials: a primer for clinicians. BMJ. 2018; 360: k698. PubMed Abstract | Publisher Full Text | Free Full Text 5. Park JJ, Thorlund K, Mills EJ: Critical concepts in adaptive clinical trials. Clin Epidemiol. 2018; 10: 343-351. PubMed Abstract | Publisher Full Text | Free Full Text 6.
doi:10.21956/gatesopenres.14050.r26986 fatcat:p4gikmfxljgedfjzyyrsrkmmy4