Keywords: clinical trial, dose-finding, cancer, oncology
In cancer clinical trials, the Common Terminology Criteria for Adverse Events (CTCAE) guidelines published by the NCI define hundreds of adverse events, graded on a scale of 0-5, to describe patient toxicities used to define the primary endpoint in dose-finding trials. However, conventional trial methodology simplifies this comprehensive system to a binary toxicity endpoint, which in the era of targeted agents and immunotherapies, may inadequately reflect a patient's true toxicity burden. Novel trial designs have introduced the concept of composite toxicity scores to reflect the severity of several adverse events over varying grades, but standard methodology for eliciting such scores has yet to be developed. In consideration of this, we propose a novel method for estimating toxicity scores through a cumulative logit model; toxicity scores are assumed to be a latent variable characterized by the corresponding set of adverse events and toxicity grades, which manifest as ordinal outcomes relating to clinically intuitive dose-escalation decisions. The proposed methodology provides a tool for allowing an intuitive and easier adoption of toxicity scores into clinical practice.