Novel dose-finding designs and considerations on practical implementations in oncology clinical trials

Journal of Biopharmaceutical Statistics
Bo HuangEnayet Talukder

Abstract

One of the main objectives in phase I oncology trials is to evaluate safety and tolerability of an experimental treatment by estimating the maximum tolerated dose (MTD) based on the rate of dose-limiting toxicities (DLT). To meet emerging challenges in dose-finding studies, over the past two decades, extensive research has been conducted by statistical and medical researchers to create innovative dose finding designs that perform better than the standard 3 + 3 design, which often exhibits undesirable statistical and operational properties. However, clinical implementation and practical usage of these new designs have been limited. This article begins with a review of the most recent literature and then provides some perspectives on implementing novel adaptive dose finding designs in oncology phase I trials from a pharmaceutical industry perspective. Statistical planning and logistical considerations on how to effectively execute such designs in multi-center clinical trials are discussed using two recent case studies.

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Citations

Dec 6, 2019·Journal for Immunotherapy of Cancer·Ezra E W CohenSteven F Powell
Jun 22, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Anthony W TolcherLaura Q M Chow
Mar 20, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Neil H SegalAjay K Gopal
Mar 8, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ajay K GopalNancy L Bartlett

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Clinical Trials Mentioned

NCT01307267
NCT01876251

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CRM
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Interactive Voice Response System ( IVRS )
EAST ESCALATE
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