Repository logo
 

Bayesian adaptive bandit-based designs using the Gittins index for multi-armed trials with normally distributed endpoints

Published version
Peer-reviewed

Type

Article

Change log

Authors

Smith, AL 
Villar Moreschi, Sofia  ORCID logo  https://orcid.org/0000-0001-7755-2637

Abstract

Adaptive designs for multi-armed clinical trials have become increasingly popular recently because of their potential to shorten development times and to increase patient response. However, developing response-adaptive designs that offer patient-benefit while ensuring the resulting trial provides a statistically rigorous and unbiased comparison of the different treatments included is highly challenging. In this paper, the theory of Multi-Armed Bandit Problems is used to define near optimal adaptive designs in the context of a clinical trial with a normally distributed endpoint with known variance. We report the operating characteristics (type I error, power, bias) and patient-benefit of these approaches and alternative designs using simulation studies based on an ongoing trial. These results are then compared to those recently published in the context of Bernoulli endpoints. Many limitations and advantages are similar in both cases but there are also important differences, specially with respect to type I error control. This paper proposes a simulation-based testing procedure to correct for the observed type I error inflation that bandit-based and adaptive rules can induce.

Description

Keywords

multi-armed bandit, Gittins index, response adaptive procedures, normally distributed endpoint, sequential sampling, patient allocation

Journal Title

Journal of Applied Statistics

Conference Name

Journal ISSN

0266-4763
1360-0532

Volume Title

Publisher

Taylor & Francis
Sponsorship
MRC (unknown)
Biometrika Trust (unknown)
This work was funded by the Biometrika Trust and the UK Medical Research Council (grant number MC_UP_1302/2).