PKL-Optimality Criterion in Copula Models for Efficacy-Toxicity Response
In recent years, there has been an increasing interest in developing dose finding methods incorporating both efficacy and toxicity outcomes. It is reasonable to assume that efficacy and toxicity are associated; therefore, we need to model their stochastic dependence. Copula functions are very useful tools to model different kinds of dependence with arbitrary marginal distributions. We consider a binary efficacy-toxicity response with logit marginal distributions. Since the dose which maximizes the probability of efficacy without toxicity (P-optimal dose) changes depending on different copula functions, we propose a criterion which is useful for choosing between the rival copula models but also protects patients against doses that are far away from the P-optimal dose. The performance of this compromise criterion (called PKL) is illustrated for different choices of the parameter values.
KeywordsMarginal Distribution Maximum Tolerate Dose Dependence Structure Dependence Parameter Tail Dependence
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