A preplanned multi-stage platform trial for discovering multiple superior treatments with control of FWER and power

TL;DR

This paper proposes a multi-stage platform trial design that allows adding new treatments while controlling error rates, and analyzes sample size and power considerations for detecting multiple superior treatments.

Contribution

It introduces a preplanned multi-stage platform trial methodology that maintains family-wise error rate control while allowing treatment additions and evaluates its sample size and power properties.

Findings

Sample size calculations for desired power levels.

Comparison shows platform trials may not always reduce sample size.

Method enables adding treatments without inflating error rates.

Abstract

There is a growing interest in the implementation of platform trials, which provide the flexibility to incorporate new treatment arms during the trial and the ability to halt treatments early based on lack of benefit or observed superiority. In such trials, it can be important to ensure that error rates are controlled. This paper introduces a multi-stage design that enables the addition of new treatment arms, at any point, in a pre-planned manner within a platform trial, while still maintaining control over the family-wise error rate. This paper focuses on finding the required sample size to achieve a desired level of statistical power when treatments are continued to be tested even after a superior treatment has already been found. This may be of interest if there are other sponsors treatments which are also superior to the current control or multiple doses being tested. The calculations to determine the expected sample size is given. A motivating trial is presented in which the sample size of different configurations is studied. Additionally the approach is compared to running multiple separate trials and it is shown that in many scenarios if family wise error rate control is needed there may not be benefit in using a platform trial when comparing the sample size of the trial.