New Paradigm in Dose-Finding Trials: Patient-Specific Dosing and Beyond Phase I
نویسندگان
چکیده
منابع مشابه
New paradigm in dose-finding trials: patient-specific dosing and beyond phase I.
We propose a new paradigm for the clinical evaluation of new cancer therapies. It entails adjusting the search for the optimal dose on the basis of measurable patient characteristics that may be predictive of adverse responses to treatment, and extending this search beyond phase I and into phases II and III. We provide examples of (a) how the fine-tuning of dose may involve utilization of patie...
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BACKGROUND Statistical simulations have consistently demonstrated that new dose-escalation designs such as accelerated titration design (ATD) and continual reassessment method (CRM)-type designs outperform the standard "3+3" design in phase I cancer clinical trials. METHODS We evaluated the actual efficiency of different dose escalation methods employed in first-in-human phase I clinical tria...
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Phase I clinical trials aim to find the maximum tolerated dose of an experimental drug. We consider dose escalation, de-escalation, or staying at the current dose as three different stochastic moves over the lattice of a sequence of prespecified dose levels. Each move is chosen by minimizing an expected penalty that determines the dose level for treating the next cohort of patients. We develop ...
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A rapidly increasing number of Phase I dose-finding studies, and in particular those based on the standard 3+3 design, are being prolonged with the inclusion of dose expansion cohorts (DEC) in order to better characterize the toxicity profiles of experimental agents and to study disease-specific cohorts. These trials consist of two phases: the usual dose escalation phase that aims to establish ...
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A Bayesian adaptive design is proposed for dose-finding in phase I/II clinical trials to incorporate the bivariate outcomes, toxicity and efficacy, of a new treatment. Without specifying any parametric functional form for the drug dose-response curve, we jointly model the bivariate binary data to account for the correlation between toxicity and efficacy. After observing all the responses of eac...
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ژورنال
عنوان ژورنال: Clinical Cancer Research
سال: 2005
ISSN: 1078-0432,1557-3265
DOI: 10.1158/1078-0432.ccr-05-0458