Statistics in medicine
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Statistics in medicine · Jan 2017
A Bayesian adaptive design for estimating the maximum tolerated dose curve using drug combinations in cancer phase I clinical trials.
We present a cancer phase I clinical trial design of a combination of two drugs with the goal of estimating the maximum tolerated dose curve in the two-dimensional Cartesian plane. A parametric model is used to describe the relationship between the doses of the two agents and the probability of dose limiting toxicity. The model is re-parameterized in terms of the probabilities of toxicities at dose combinations corresponding to the minimum and maximum doses available in the trial and the interaction parameter. ⋯ Performance of the trial is studied by evaluating its design operating characteristics in terms of safety of the trial and percent of dose recommendation at dose combination neighborhoods around the true MTD curve and under model misspecifications for the true dose-toxicity relationship. The method is further extended to accommodate discrete dose combinations and compared with previous approaches under several scenarios. Copyright © 2016 John Wiley & Sons, Ltd.
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Statistics in medicine · Jan 2017
Goodness-of-fit test for monotone proportional subdistribution hazards assumptions based on weighted residuals.
Recently goodness-of-fit tests have been proposed for checking the proportional subdistribution hazards assumptions in the Fine and Gray regression model. Zhou, Fine, and Laird proposed weighted Schoenfeld-type residuals tests derived under an assumed model with specific form of time-varying regression coefficients. Li, Sheike, and Zhang proposed an omnibus test based on cumulative sums of Schoenfeld-type residuals. ⋯ Results from simulation studies show that weighted residuals tests using monotone random weight functions commonly used in non-proportional hazards regression settings tend to be more powerful for detecting monotone departures than other goodness-of-fit tests assuming no specific time-varying effect or misspecified time-varying effects. Two examples using real data are provided for illustrations. Copyright © 2016 John Wiley & Sons, Ltd.