Direkt zum Inhalt

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 und Jaki, Thomas (2023) Point estimation for adaptive trial designs II: Practical considerations and guidance. Statistics in Medicine 42 (14), S. 2496-2520.

Veröffentlichungsdatum dieses Volltextes: 18 Mrz 2025 10:06
Artikel
DOI zum Zitieren dieses Dokuments: 10.5283/epub.75876


Zusammenfassung

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.



Beteiligte Einrichtungen


Details

DokumentenartArtikel
Titel eines Journals oder einer ZeitschriftStatistics in Medicine
Verlag:Wiley
Ort der Veröffentlichung:HOBOKEN
Band:42
Nummer des Zeitschriftenheftes oder des Kapitels:14
Seitenbereich:S. 2496-2520
Datum5 April 2023
InstitutionenInformatik und Data Science > Fachbereich Maschinelles Lernen und Data Science > Chair for Computational Statistics (Prof. Dr. Thomas Jaki)
Identifikationsnummer
WertTyp
10.1002/sim.9734DOI
Stichwörter / 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-Dezimal-Klassifikation000 Informatik, Informationswissenschaft, allgemeine Werke > 004 Informatik
StatusVeröffentlicht
BegutachtetJa, diese Version wurde begutachtet
An der Universität Regensburg entstandenZum Teil
URN der UB Regensburgurn:nbn:de:bvb:355-epub-758761
Dokumenten-ID75876

Bibliographische Daten exportieren

Nur für Besitzer und Autoren: Kontrollseite des Eintrags

nach oben