Choodari-Oskooei, Babak;
Robertson, David S;
(2025)
Confidence Intervals for Adaptive Trial Designs I: A Methodological Review.
Statistics in Medicine
, 44
(18-19)
, Article e70174. 10.1002/sim.70174.
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Abstract
Regulatory guidance notes the need for caution in the interpretation of confidence intervals (CIs) constructed during and after an adaptive clinical trial. Conventional CIs of the treatment effects are prone to undercoverage (as well as other undesirable properties) in many adaptive designs (ADs) because they do not take into account the potential and realized trial adaptations. This paper is the first in a two-part series that explores CIs for adaptive trials. It provides a comprehensive review of the methods to construct CIs for ADs, while the second paper illustrates how to implement these in practice and proposes a set of guidelines for trial statisticians. We describe several classes of techniques for constructing CIs for adaptive clinical trials before providing a systematic literature review of available methods, classified by the type of AD. As part of this, we assess, through a proposed traffic light system, which of several desirable features of CIs (such as achieving nominal coverage and consistency with the hypothesis test decision) each of these methods holds.
| Type: | Article |
|---|---|
| Title: | Confidence Intervals for Adaptive Trial Designs I: A Methodological Review |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/sim.70174 |
| Publisher version: | https://doi.org/10.1002/sim.70174 |
| 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, coverage, estimation, flexible design, group sequential, interim analyses, repeated 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/10212143 |
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