Dose finding studies for therapies with late-onset toxicities: A comparison study of designs.
dose-finding
late-onset toxicities
model-assisted
model-based
phase I trials
Journal
Statistics in medicine
ISSN: 1097-0258
Titre abrégé: Stat Med
Pays: England
ID NLM: 8215016
Informations de publication
Date de publication:
30 12 2022
30 12 2022
Historique:
revised:
28
07
2022
received:
30
04
2021
accepted:
03
10
2022
pubmed:
18
10
2022
medline:
16
12
2022
entrez:
17
10
2022
Statut:
ppublish
Résumé
An objective of phase I dose-finding trials is to find the maximum tolerated dose; the dose with a particular risk of toxicity. Frequently, this risk is assessed across the first cycle of therapy. However, in oncology, a course of treatment frequently consists of multiple cycles of therapy. In many cases, the overall risk of toxicity for a given treatment is not fully encapsulated by observations from the first cycle, and hence it is advantageous to include toxicity outcomes from later cycles in phase I trials. Extending the follow up period in a trial naturally extends the total length of the trial which is undesirable. We present a comparison of eight methods that incorporate late onset toxicities while not extensively extending the trial length. We conduct simulation studies over a number of scenarios and in two settings; the first setting with minimal stopping rules and the second setting with a full set of standard stopping rules expected in such a dose finding study. We find that the model-based approaches in general outperform the model-assisted approaches, with an interval censored approach and a modified version of the time-to-event continual reassessment method giving the most promising overall performance in terms of correct selections and trial length. Further recommendations are made for the implementation of such methods.
Identifiants
pubmed: 36250912
doi: 10.1002/sim.9593
pmc: PMC10092569
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5767-5788Subventions
Organisme : Department of Health
ID : NIHR-SRF-2015-08-001
Pays : United Kingdom
Organisme : Department of Health
ID : BRC-1215-20014
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00002/14
Pays : United Kingdom
Informations de copyright
© 2022 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.
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