A preplanned multi-stage platform trial for discovering multiple superior treatments with control of FWER and power
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.
A multi-arm multi-stage platform design that allows pre-planned
addition of arms while still controlling the family-wise error
Abstract: There is growing interest in platform trials that allow for adding of new treatment arms as the trial progresses as well as being able to stop treatments part way through the trial for either lack of benefit/futility or for superiority. In some situations, platform trials need to guarantee that error rates are controlled. This paper presents a multi-stage design that allows additional arms to be added in a platform trial in a preplanned fashion, while still controlling the family wise error rate. A method is given to compute the sample size required to achieve a desired level of power and we show how the distribution of the sample size and the expected sample size can be found. A motivating trial is presented which focuses on two settings, with the first being a set number of stages per active treatment arm and the second being a set total number of stages, with treatments that are added later getting fewer stages. Through this example we show that the proposed method results in a smaller sample size while still controlling the errors compared to running multiple separate trials.
Satellites What Harm Can They Do?
Before University I competed in a competition for the IOP Environmental Physics Group. My work received a highly recommended award. My article was on the effects that satellites have on the environment.