Proportional odds assumption for modeling longitudinal ordinal multiple toxicity outcomes in dose finding studies of targeted agents: A pooled analysis of 54 studies.

ABSTRACT:

Background

Data generated by phase I trials is richer than the classical binary DLT measured at the first cycle used as primary endpoints. Several works developed designs for more informative endpoints, e.g. ordinal toxicity grades and/or longitudinal data which relied however on strong assumptions, in particular the proportional odds (PO) assumption.

Methods

We evaluated this PO assumption for the dose and cycle on a large database of individual patient data from 54 phase I clinical trials of molecularly targeted agents. The PO model is a specific case of the continuation ratio logit model (CRLM) with null parameters. We compared the PO and CRLM models using the widely applicable information criterion (WAIC). We considered a longitudinal multivariate ordinal toxicity outcom

SUBMITTER: Drubay D 

PROVIDER: S-EPMC7005415 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature