کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6151362 1231518 2012 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Dose escalation with overdose control using a quasi-continuous toxicity score in cancer Phase I clinical trials
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی پزشکی و دندانپزشکی (عمومی)
پیش نمایش صفحه اول مقاله
Dose escalation with overdose control using a quasi-continuous toxicity score in cancer Phase I clinical trials
چکیده انگلیسی
Escalation with overdose control (EWOC) is a Bayesian adaptive design for selecting dose levels in cancer Phase I clinical trials while controlling the posterior probability of exceeding the maximum tolerated dose (MTD). EWOC has been used by clinicians to design many cancer Phase I clinical trials, see e.g. [1-4]. However, this design treats the toxicity response as a binary indicator of dose limiting toxicity (DLT) and does not account for the number and specific grades of toxicities experienced by patients during the trial. Chen et al. (2010) proposed a novel toxicity score system to fully utilize all toxicity information using a normalized equivalent toxicity score (NETS). In this paper, we propose to incorporate NETS into EWOC using a quasi-Bernoulli likelihood approach to design cancer Phase I clinical trials. We call the design escalation with overdose control using normalized equivalent toxicity score (EWOC-NETS). Simulation results show that this design has good operating characteristics and improves the accuracy of MTD, trial efficiency, therapeutic effect, and overdose control relative to EWOC which is used as a representative of designs treating toxicity response as a binary indicator of DLT. We illustrate the performance of this design using real trial data in identifying the Phase II dose.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Contemporary Clinical Trials - Volume 33, Issue 5, September 2012, Pages 949-958
نویسندگان
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