A flexible design for advanced Phase I/II clinical trials with continuous efficacy endpoints.

08:00 EDT 12th July 2019 | BioPortfolio

Summary of "A flexible design for advanced Phase I/II clinical trials with continuous efficacy endpoints."

There is growing interest in integrated Phase I/II oncology clinical trials involving molecularly targeted agents (MTA). One of the main challenges of these trials are nontrivial dose-efficacy relationships and administration of MTAs in combination with other agents. While some designs were recently proposed for such Phase I/II trials, the majority of them consider the case of binary toxicity and efficacy endpoints only. At the same time, a continuous efficacy endpoint can carry more information about the agent's mechanism of action, but corresponding designs have received very limited attention in the literature. In this work, an extension of a recently developed information-theoretic design for the case of a continuous efficacy endpoint is proposed. The design transforms the continuous outcome using the logistic transformation and uses an information-theoretic argument to govern selection during the trial. The performance of the design is investigated in settings of single-agent and dual-agent trials. It is found that the novel design leads to substantial improvements in operating characteristics compared to a model-based alternative under scenarios with nonmonotonic dose/combination-efficacy relationships. The robustness of the design to missing/delayed efficacy responses and to the correlation in toxicity and efficacy endpoints is also investigated.


Journal Details

This article was published in the following journal.

Name: Biometrical journal. Biometrische Zeitschrift
ISSN: 1521-4036


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Comparative studies to verify the effectiveness of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques determined in phase II studies. During these trials, patients are monitored closely by physicians to identify any adverse reactions from long-term use. These studies are performed on groups of patients large enough to identify clinically significant responses and usually last about three years. This concept includes phase III studies conducted in both the U.S. and in other countries.

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