Statistics in medicine
-
Statistics in medicine · Jul 2005
Comparative StudyFlexible Bayesian methods for cancer phase I clinical trials. Dose escalation with overdose control.
We examine a large class of prior distributions to model the dose-response relationship in cancer phase I clinical trials. We parameterize the dose-toxicity model in terms of the maximum tolerated dose (MTD) gamma and the probability of dose limiting toxicity (DLT) at the initial dose rho(0). The MTD is estimated using the EWOC (escalation with overdose control) method of Babb et al. We show through simulations that a candidate joint prior for (rho0,gamma) with negative a priori correlation structure results in a safer trial than the one that assumes independent priors for these two parameters while keeping the efficiency of the estimate of the MTD essentially unchanged.
-
Statistics in medicine · Jul 2005
Dose escalation trial designs based on a molecularly targeted endpoint.
Traditional phase I dose-finding studies for chemotoxic agents base dose escalation on toxicity, with escalation continuing until unacceptable toxicity is observed. Recent development of molecularly targeted agents that have little or no toxicity in the therapeutic dose range has raised questions over the best study designs for phase I studies. Two types of designs are proposed and evaluated in this paper. ⋯ One design is developed to ensure that if the true target response rate is low there will be a high probability of escalating and if the true target response rate is high there will be a low probability of escalating. The other design is developed to continue to escalate as long as the true response rate is increasing and to stop escalating when the response rate plateaus or decreases. A limited simulation study is performed and the designs are compared with respect to the dose level at the end of escalation and the number of patients treated on study.