2024/11/13 by David S. Robertson, Thomas J Burnett, Robertson, David S. +15 · 1 voice · 1 citation
Decision Sciences · Economics, Econometrics and Finance · Mathematics · #Health Systems, Economic Evaluations, Quality of Life #Meta-analysis and systematic reviews #Statistical Methods in Clinical Trials #stat.AP #stat.ME
paper · pdf · doi:10.48550/arxiv.2411.08495
openalex publication_date 2024/11/13 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
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, because they do not take into account the potential and realised 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 adaptive designs, 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 adaptive design. 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.