Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
Results
Showing 1 to 19 of 19 for “"Dose-Finding"”.
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Adaptive designs for complex dose finding studies
… phase clinical trial is to find the regimen (dose, combination, schedule, etc.) satisfying particular toxicity or (and) efficacy characteristics. Designs for trials studying doses of a single cytotoxic drug are based on the fundamental assumption "the more the better", that is, the toxicity …
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Bayesian Phase I Dose Finding In Cancer Trials
<p>This dissertation explores phase I dose-finding designs in cancer trials from three perspectives: the alternative Bayesian dose-escalation rules, a design based on a time-to-dose-limiting toxicity (DLT) model, and a design based on a discrete-time multi-state (DTMS) model.</p> <p>We list …
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Optimal designs for dose-finding in contingent response models
We study D- and c-optimal designs for dose-finding with opposing failure functions. In particular, we study the contingent response models of Li, Durham and Flournoy (1995). In the contingent response model, there are two opposing types of failure. We call one failure type toxicity and the other …
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Dual-Criterion Dose Finding Designs for Phase I Clinical Trials
… tolerability of novel therapeutics. Conventional dose escalation methods identify the maximum tolerated dose (MTD) based on dose-limiting toxicity (DLT). However, as cancer therapies have evolved from chemotherapy to targeted therapies, these traditional methods have become problematic. Many …
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Bayesian Semi-Mechanistic Dose-Finding Designs For Phase I Oncology Trials
… In oncology, despite the great advances in novel dose-finding designs, the high failure rates of clinical cancer drug development from phase I to III trials call for further improvements on novel designs, in addition to the need to promote and adopt novel designs in practice. Because anticancer …
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An Adaptive Dose Finding Design (DOSEFIND) Using A Nonlinear Dose Response Model
… 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, …
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The application of Bayesian adaptive design and Markov model in clinical trials
… The first problem is a new Bayesian adaptive dose-finding design and its application in an oncology clinical trial. This design is used for phase IB studies with the biomarker as the endpoint and with the fewer patients. The second problem is another new Bayesian adaptive dose-finding design …
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Bayesian Adaptive Clinical Trial Design
… and dysfunctional. Specifically, the focus of dose-finding trials has shifted from finding the maximum tolerated dose (MTD) to the optimal biological dose (OBD), defined as the dose that optimizes the risk–benefit tradeoff. How to accurately identify the OBD and its dosing schedule is of great …
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The Use of Action Observation and Imitation in the Treatment of Upper Limb Paresis Early After Stroke
… after stroke to justify proceeding to subsequent dose finding (phase I) and efficacy (phase II) trials. Methods: Seventeen individuals with moderate/severe UL limb paresis 3 to 31 days following ischaemic/haemorrhagic stroke were recruited. Those who were able to imitate an action were randomly …
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Modified 3+3 Design for MTD Re-estimation
… clinical trial design is one of the most popular dose-finding designs used in phase I oncology trials to identify the maximum tolerated dose (MTD) for new treatment regimens. While this design is widely used due to its simplicity , it has some notable limitations, including a maximum of six …
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An Adaptive Bayesian Approach to Bernoulli-Response Clinical Trials
… 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 …
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Bayesian Adaptive Designs For Early Phase Clinical Trials
… proposing a novel two-dimensional dose-finding algorithm for biological agents, <strong>(2)</strong> developing Bayesian adaptive screening designs to provide more efficient and ethical clinical trials, and <strong>(3)</strong> incorporating missing late-onset responses to make an …
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Novel Phase I/II Designs for Cytotoxic and Cytostatic Agents, and Combination Treatments
… develops innovative Bayesian adaptive dose-finding designs for early-phase oncology trials, aiming to improve the identification of optimal biological doses (OBDs) by jointly modeling safety and efficacy. Unlike conventional Phase I designs that rely solely on binary toxicity outcomes …
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Integrating Cell-level Kinetic Modeling into the Optimization of Cancer Therapeutics
… when pharmacokinetic modeling is used to guide dose finding and analyze preclinical or clinical in vivo data. This is especially critical for therapeutic proteins where, due to the degradation mediated by the targeted receptor, drug effect and pharmacokinetics are inherently interdependent. This …
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Bayesian Adaptive Designs for Early Phase Clinical Trials
… outcome issue for the 3+3 design. We convert the dose decision rules of the 3+3 design into a series of events. A transparent yet efficient Bayesian probability model is applied to calculate the event happening probabilities in the presence of delayed outcomes, which incorporates the informative …
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Vitamin D and calcium supplementation for reducing hip fractures in the elderly.
… fractures in monetary terms. Additionally, more dose finding studies and studies addressing the male gender needs to be done.
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Investigations of Pharmacokinetic Challenges in Premature Infants
… were developed based on the PopPK model and dose-finding simulation study.</p> <p>Due to the limitation in sample volume, an assay that can simultaneously determine multiple drugs allows for gaining maximal information from PK studies while minimizing the burden of blood collection in …
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Bayesian Designs For Early Phase Clinical Trials With Novel Target Agents
… have been proposed to find the maximum tolerated dose (MTD) in phase I clinical trials, but their differences and relative pros and cons are not clear to many practitioners. We review three model-based designs, including the continual reassessment method (CRM), dose escalation with overdose …