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Combined criteria for dose optimisation in early phase clinical trials
Author(s) -
Alam M. Iftakhar,
Coad D. Stephen,
Bogacka Barbara
Publication year - 2019
Publication title -
statistics in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.996
H-Index - 183
eISSN - 1097-0258
pISSN - 0277-6715
DOI - 10.1002/sim.8292
Subject(s) - maximum tolerated dose , computer science , outcome (game theory) , fisher information , clinical trial , trinomial , mathematical optimization , medicine , mathematics , machine learning , mathematical economics , discrete mathematics
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.