Abstract
Background: Adaptive designs and platform designs are among two 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. Results: In this article we introduce a simple intuitive open-source browser-based clinical trial simulator for planning adaptive and platform trials. The software application is implemented in RShiny and features a 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. Conclusion: We have developed and validated an intuitive highly efficient 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: https://mtek.shinyapps.io/hect/.
Highlights
Over the past two decades randomized clinical trials have become increasingly innovative[1]
Adaptive designs and platform designs are among two common clinical trial innovations that are increasingly being used by the pharmaceutical industry to manage their drug portfolios and get to faster regulatory approvals of new treatments[2,3,4]
Contrary to conventional randomized clinical trials where all patients are followed-up after a fixed period of time and the pre-planned trial protocol is adhered without deviation, adaptive trials and platform designs allow for pre-planned modifications to the protocol in the event of strong early treatment response signals[4]
Summary
Any reports and responses or comments on the article can be found at the end of the article. Author roles: Thorlund K: Conceptualization, Investigation, Methodology, Project Administration, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing; Golchi S: Conceptualization, Formal Analysis, Investigation, Methodology, Project Administration, Software, Validation, Visualization, Writing – Review & Editing; Haggstrom J: Conceptualization, Investigation, Methodology, Supervision, Writing – Review & Editing; Mills E: Conceptualization, Funding Acquisition, Investigation, Methodology, Supervision, Visualization, Writing – Review & Editing. We have updated some of the sentences in the Validation and Use Cases section due to vague language in the first version. We believe the text accurately reflects the intersecting stages of validation and use cases that the software has gone through prior to its release
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