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Combined criteria for dose optimisation in early phase clinical trials.

Authors :
Alam, M. Iftakhar
Coad, D. Stephen
Bogacka, Barbara
Source :
Statistics in Medicine; 9/20/2019, Vol. 38 Issue 21, p4172-4188, 17p
Publication Year :
2019

Abstract

This paper aims to investigate whether any bridge is possible between so-called best intention and D-optimum designs. It introduces combined criteria for dose optimisation in seamless phase I/II adaptive clinical trials. Each of the optimality criteria considers efficacy and toxicity as endpoints and is based on the probability of a successful outcome and on the determinant of the Fisher information matrix for estimation of the dose-response parameters. In addition, one of the criteria incorporates penalties for choosing a toxic or inefficacious dose. Starting with the lowest dose, the adaptive design selects the dose for each subsequent cohort that maximises the respective defined criterion. The methodology is illustrated with a dose-response model that assumes trinomial responses. Simulation studies show that the method is capable of identifying the optimal dose accurately without exposing many patients to toxic doses. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
02776715
Volume :
38
Issue :
21
Database :
Complementary Index
Journal :
Statistics in Medicine
Publication Type :
Academic Journal
Accession number :
137988090
Full Text :
https://doi.org/10.1002/sim.8292