Probability intervals of toxicity and efficacy design for dose-finding clinical trials in oncology.

Abstract:

:Immunotherapy, gene therapy or adoptive cell therapies, such as the chimeric antigen receptor+ T-cell therapies, have demonstrated promising therapeutic effects in oncology patients. We consider statistical designs for dose-finding adoptive cell therapy trials, in which the monotonic dose-response relationship assumed in traditional oncology trials may not hold. Building upon a previous design called "TEPI", we propose a new dose finding method - Probability Intervals of Toxicity and Efficacy (PRINTE), which utilizes toxicity and efficacy jointly in making dosing decisions, does not require a pre-elicited decision table and at the same time can handle Ockham's razor properly in the statistical inference. We show that optimizing the joint posterior expected utility of toxicity and efficacy under a 0-1 loss is equivalent to maximizing the marginal model posterior probability in the two-dimensional probability space. An extensive simulation study under various scenarios are conducted and results show that PRINTE outperforms existing designs in the literature since it assigns more patients to optimal doses and less to toxic ones, and selects optimal doses with higher percentages. The simple and transparent features together with good operating characteristics make PRINTE an improved design for dose-finding trials in oncology trials.

journal_name

Stat Methods Med Res

authors

Lin X,Ji Y

doi

10.1177/0962280220977009

subject

Has Abstract

pub_date

2020-12-16 00:00:00

pages

962280220977009

eissn

0962-2802

issn

1477-0334

pub_type

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