Choodari-Oskooei, Babak;
Robertson, David S;
(2025)
Confidence Intervals for Adaptive Trial Designs II: Case Study and Practical Guidance.
Statistics in Medicine
, 44
(18-19)
, Article e70202. 10.1002/sim.70202.
Preview |
Text
Statistics in Medicine - 2025 - Robertson - Confidence Intervals for Adaptive Trial Designs II Case Study and Practical.pdf - Published Version Download (519kB) | Preview |
Abstract
In adaptive clinical trials, the conventional confidence interval (CI) for a treatment effect is prone to undesirable properties such as undercoverage and potential inconsistency with the final hypothesis testing decision. Accordingly, as is stated in recent regulatory guidance on adaptive designs, there is the need for caution in the interpretation of CIs constructed during and after an adaptive clinical trial. However, it may be unclear which of the available CIs in the literature are preferable. This paper is the second in a two-part series that explores CIs for adaptive trials. Part I provided a methodological review of approaches to construct CIs for adaptive designs. In this paper (Part II), we present an extended case study based around a two-stage group sequential trial, including a comprehensive simulation study of the proposed CIs for this setting. This facilitates an expanded description of considerations around what makes for an effective CI procedure following an adaptive trial. We show that the CIs can have notably different properties. Finally, we propose a set of guidelines for researchers around the choice of CIs and the reporting of CIs following an adaptive design.
| Type: | Article |
|---|---|
| Title: | Confidence Intervals for Adaptive Trial Designs II: Case Study and Practical Guidance |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/sim.70202 |
| Publisher version: | https://doi.org/10.1002/sim.70202 |
| Language: | English |
| Additional information: | Copyright © 2025 The Author(s). Statistics in Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | adaptive design, bootstrap, conditional inference, coverage, estimation, group sequential, interim analyses |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10212198 |
Archive Staff Only
 |
View Item |
