Saved in:
Bibliographic Details
Main Authors: Robertson, David S., Burnett, Thomas, Choodari-Oskooei, Babak, Dimairo, Munya, Grayling, Michael, Pallmann, Philip, Jaki, Thomas
Format: Preprint
Published: 2024
Subjects:
Online Access:https://arxiv.org/abs/2411.08495
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1866917835968610304
author Robertson, David S.
Burnett, Thomas
Choodari-Oskooei, Babak
Dimairo, Munya
Grayling, Michael
Pallmann, Philip
Jaki, Thomas
author_facet Robertson, David S.
Burnett, Thomas
Choodari-Oskooei, Babak
Dimairo, Munya
Grayling, Michael
Pallmann, Philip
Jaki, Thomas
contents 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.
format Preprint
id arxiv_https___arxiv_org_abs_2411_08495
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle Confidence intervals for adaptive trial designs I: A methodological review
Robertson, David S.
Burnett, Thomas
Choodari-Oskooei, Babak
Dimairo, Munya
Grayling, Michael
Pallmann, Philip
Jaki, Thomas
Methodology
Applications
62F25
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.
title Confidence intervals for adaptive trial designs I: A methodological review
topic Methodology
Applications
62F25
url https://arxiv.org/abs/2411.08495