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Burdon, Abigail J. ; Baird, Richard D. ; Jaki, Thomas

Adaptive enrichment trial designs using joint modelling of longitudinal and time-to-event data

Burdon, Abigail J., Baird, Richard D. und Jaki, Thomas (2024) Adaptive enrichment trial designs using joint modelling of longitudinal and time-to-event data. Statistical Methods in Medical Research 33 (11-12), S. 2098-2114.

Veröffentlichungsdatum dieses Volltextes: 22 Sep 2025 06:46
Artikel
DOI zum Zitieren dieses Dokuments: 10.5283/epub.77768


Zusammenfassung

Adaptive enrichment allows for pre-defined patient subgroups of interest to be investigated throughout the course of a clinical trial. These designs have gained attention in recent years because of their potential to shorten the trial's duration and identify effective therapies tailored to specific patient groups. We describe enrichment trials which consider long-term time-to-event outcomes but ...

Adaptive enrichment allows for pre-defined patient subgroups of interest to be investigated throughout the course of a clinical trial. These designs have gained attention in recent years because of their potential to shorten the trial's duration and identify effective therapies tailored to specific patient groups. We describe enrichment trials which consider long-term time-to-event outcomes but also incorporate additional short-term information from routinely collected longitudinal biomarkers. These methods are suitable for use in the setting where the trajectory of the biomarker may differ between subgroups and it is believed that the long-term endpoint is influenced by treatment, subgroup and biomarker. Methods are most promising when the majority of patients have biomarker measurements for at least two time points. We implement joint modelling of longitudinal and time-to-event data to define subgroup selection and stopping criteria and we show that the familywise error rate is protected in the strong sense. To assess the results, we perform a simulation study and find that, compared to the study where longitudinal biomarker observations are ignored, incorporating biomarker information leads to increases in power and the (sub)population which truly benefits from the experimental treatment being enriched with higher probability at the interim analysis. The investigations are motivated by a trial for the treatment of metastatic breast cancer and the parameter values for the simulation study are informed using real-world data where repeated circulating tumour DNA measurements and HER2 statuses are available for each patient and are used as our longitudinal data and subgroup identifiers, respectively.



Beteiligte Einrichtungen


Details

DokumentenartArtikel
Titel eines Journals oder einer ZeitschriftStatistical Methods in Medical Research
Verlag:Sage
Band:33
Nummer des Zeitschriftenheftes oder des Kapitels:11-12
Seitenbereich:S. 2098-2114
Datum16 Oktober 2024
InstitutionenInformatik und Data Science > Fachbereich Maschinelles Lernen und Data Science > Chair for Computational Statistics (Prof. Dr. Thomas Jaki)
Identifikationsnummer
WertTyp
10.1177/09622802241287711DOI
Stichwörter / KeywordsEfficient designs, enrichment, joint modelling, longitudinal data, time-to-event data
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-777689
Dokumenten-ID77768

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