Assessing toxicities in a clinical trial: Bayesian inference for ordinal data nested within categories.

This article addresses modeling and inference for ordinal outcomes nested within categorical responses. We propose a mixture of normal distributions for latent variables associated with the ordinal data. This mixture model allows us to fix without loss of generality the cutpoint parameters that link the latent variable with the observed ordinal outcome. Moreover, the mixture model is shown to be more flexible in estimating cell probabilities when compared to the traditional Bayesian ordinal probit regression model with random cutpoint parameters. We extend our model to take into account possible dependence among the outcomes in different categories. We apply the model to a randomized phase III study to compare treatments on the basis of toxicities recorded by type of toxicity and grade within type. The data include the different (categorical) toxicity types exhibited in each patient. Each type of toxicity has an (ordinal) grade associated to it. The dependence among the different types of toxicity exhibited by the same patient is modeled by introducing patient-specific random effects.