Designs for adding a treatment arm to an ongoing clinical trial

Trials
Maxine Bennett, Adrian P Mander

Abstract

For many disease areas, there are often treatments in different stages of the development process. We consider the design of a two-arm parallel group trial where it is planned to add a new experimental treatment arm during the trial. This could potentially save money, patients, time and resources; however, the addition of a treatment arm creates a multiple comparison problem. Current practice in trials when a new treatment arm has been added is to compare the new treatment only to controls randomised concurrently, and this is the setting we consider here. Furthermore, for standard multi-arm trials, optimal allocation randomises a larger number of patients to the control arm than to each experimental treatment arm. In this paper we propose an adaptive design, the aim of which is to adapt the sample size of the trial when the new treatment arm is added to control the family-wise error rate (FWER) in the strong sense, whilst maintaining the marginal power of each treatment-to-control comparison at the level of the original study. We explore optimal allocation for designs where a treatment arm is added with the aim of increasing the overall power of the study, where we define the overall power to be the probability of detecting all...Continue Reading

References

Nov 21, 2007·Journal of Biopharmaceutical Statistics·Huaibao FengShein-Chung Chow
Jul 17, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Boris FreidlinAlison Martin
Jun 2, 2012·Journal of Biopharmaceutical Statistics·Jordan J ElmWenle Zhao
Mar 24, 2015·JAMA : the Journal of the American Medical Association·Scott M BerryRoger J Lewis
Sep 21, 2016·Statistical Methods in Medical Research·Dena R HowardWalter M Gregory
Feb 24, 2018·Contemporary Clinical Trials·Michael J GraylingAdrian P Mander

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