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Full-Text Articles in Physical Sciences and Mathematics
An Adaptive Bayesian Approach To Bernoulli-Response Clinical Trials, Andrew W. Stacey
An Adaptive Bayesian Approach To Bernoulli-Response Clinical Trials, Andrew W. Stacey
Theses and Dissertations
Traditional clinical trials have been inefficient in their methods of dose finding and dose allocation. In this paper a four-parameter logistic equation is used to model the outcome of Bernoulli-response clinical trials. A Bayesian adaptive design is used to fit the logistic equation to the dose-response curve of Phase II and Phase III clinical trials. Because of inherent restrictions in the logistic model, symmetric candidate densities cannot be used, thereby creating asymmetric jumping rules inside the Markov chain Monte Carlo algorithm. An order restricted Metropolis-Hastings algorithm is implemented to account for these limitations. Modeling clinical trials in a Bayesian framework …
Phase Ii Trials Powered To Detect Activity In Tumor Subsets With Retrospective (Or Prospective) Use Of Predictive Markers, Grishma S. Sheth
Phase Ii Trials Powered To Detect Activity In Tumor Subsets With Retrospective (Or Prospective) Use Of Predictive Markers, Grishma S. Sheth
Theses and Dissertations
Classical phase II trial designs assume a patient population with a homogeneous tumor type and yield an estimate of a stochastic probability of tumor response. Clinically, however, oncology is moving towards identifying patients who are likely to respond to therapy using tumor subtyping based upon predictive markers. Such designs are called targeted designs (Simon, 2004). For a given phase I1 trial predictive markers may be defined prospectively (on the basis of previous results) or identified retrospectively on the basis of analysis of responding and non-responding tumors. For the prospective case we propose two Phase I1 targeted designs in which a) …
An Adaptive Dose Finding Design (Dosefind) Using A Nonlinear Dose Response Model, James Michael Davenport
An Adaptive Dose Finding Design (Dosefind) Using A Nonlinear Dose Response Model, James Michael Davenport
Theses and Dissertations
First-in-man (FIM) Phase I clinical trials are part of the critical path in the development of a new compound entity (NCE). Since FIM clinical trials are the first time that an NCE is dosed in human subjects, the designs used in these trials are unique and geared toward patient safety. We develop a method for obtaining the desired response using an adaptive non-linear approach. This method is applicable for studies in which MTD, NOEL,NOAEL, PK, PD effects or other such endpoints are evaluated to determine the desired dose. The method has application whenever a measurable PD marker is an indicator …