Robertson, D.S., Choodari‐Oskooei, B., Dimairo, M. orcid.org/0000-0002-9311-6920 et al. (3 more authors) (2023) Point estimation for adaptive trial designs I: a methodological review. Statistics in Medicine, 42 (2). pp. 122-145. ISSN 0277-6715
Abstract
Recent FDA guidance on adaptive clinical trial designs defines bias as “a systematic tendency for the estimate of treatment effect to deviate from its true value,” and states that it is desirable to obtain and report estimates of treatment effects that reduce or remove this bias. The conventional end-of-trial point estimates of the treatment effects are prone to bias in many adaptive designs, because they do not take into account the potential and realized trial adaptations. While much of the methodological developments on adaptive designs have tended to focus on control of type I error rates and power considerations, in contrast the question of biased estimation has received relatively less attention. This article is the first in a two-part series that studies the issue of potential bias in point estimation for adaptive trials. Part I provides a comprehensive review of the methods to remove or reduce the potential bias in point estimation of treatment effects for adaptive designs, while part II illustrates how to implement these in practice and proposes a set of guidelines for trial statisticians. The methods reviewed in this article can be broadly classified into unbiased and bias-reduced estimation, and we also provide a classification of estimators by the type of adaptive design. We compare the proposed methods, highlight available software and code, and discuss potential methodological gaps in the literature.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2022 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | adaptive design; bias-correction; conditional bias; flexible design; point estimation |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Health and Related Research (Sheffield) > ScHARR - Sheffield Centre for Health and Related Research |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 02 Dec 2022 09:16 |
Last Modified: | 27 Sep 2024 00:52 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1002/sim.9605 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:193995 |
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