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Robertson, David S. ; Choodari‐Oskooei, Babak ; Dimairo, Munya ; Flight, Laura ; Pallmann, Philip ; Jaki, Thomas

Point estimation for adaptive trial designs II: Practical considerations and guidance

Robertson, David S., Choodari‐Oskooei, Babak, Dimairo, Munya , Flight, Laura, Pallmann, Philip and Jaki, Thomas (2023) Point estimation for adaptive trial designs II: Practical considerations and guidance. Statistics in Medicine 42 (14), pp. 2496-2520.

Date of publication of this fulltext: 18 Mar 2025 10:06
Article
DOI to cite this document: 10.5283/epub.75876


Abstract

In adaptive clinical trials, the conventional end-of-trial point estimate of a treatment effect is prone to bias, that is, a systematic tendency to deviate from its true value. As stated in recent FDA guidance on adaptive designs, it is desirable to report estimates of treatment effects that reduce or remove this bias. However, it may be unclear which of the available estimators are preferable, ...

In adaptive clinical trials, the conventional end-of-trial point estimate of a treatment effect is prone to bias, that is, a systematic tendency to deviate from its true value. As stated in recent FDA guidance on adaptive designs, it is desirable to report estimates of treatment effects that reduce or remove this bias. However, it may be unclear which of the available estimators are preferable, and their use remains rare in practice. This article is the second in a two-part series that studies the issue of bias in point estimation for adaptive trials. Part I provided a methodological review of approaches to remove or reduce the potential bias in point estimation for adaptive designs. In part II, we discuss how bias can affect standard estimators and assess the negative impact this can have. We review current practice for reporting point estimates and illustrate the computation of different estimators using a real adaptive trial example (including code), which we use as a basis for a simulation study. We show that while on average the values of these estimators can be similar, for a particular trial realization they can give noticeably different values for the estimated treatment effect. Finally, we propose guidelines for researchers around the choice of estimators and the reporting of estimates following an adaptive design. The issue of bias should be considered throughout the whole lifecycle of an adaptive design, with the estimation strategy prespecified in the statistical analysis plan. When available, unbiased or bias-reduced estimates are to be preferred.



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Details

Item typeArticle
Journal or Publication TitleStatistics in Medicine
Publisher:Wiley
Place of Publication:HOBOKEN
Volume:42
Number of Issue or Book Chapter:14
Page Range:pp. 2496-2520
Date5 April 2023
InstitutionsInformatics and Data Science > Department Machine Learning & Data Science > Lehrstuhl für Computational Statistics (Prof. Dr. Thomas Jaki)
Identification Number
ValueType
10.1002/sim.9734DOI
KeywordsSAMPLE-SIZE REESTIMATION; MAXIMUM-LIKELIHOOD-ESTIMATION; II/III CLINICAL-TRIALS; THE-LOSERS DESIGN; RANDOMIZED-TRIALS; CONDITIONAL ESTIMATION; HYPOTHESES SELECTION; SEQUENTIAL DESIGNS; ENRICHMENT DESIGNS; EARLY TERMINATION; adaptive design; bias-correction; conditional bias; point estimation; unconditional bias
Dewey Decimal Classification000 Computer science, information & general works > 004 Computer science
StatusPublished
RefereedYes, this version has been refereed
Created at the University of RegensburgPartially
URN of the UB Regensburgurn:nbn:de:bvb:355-epub-758761
Item ID75876

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