A Bayesian dose-finding procedure for phase I clinical trials based only on the assumption of monotonicity.

Statistics in Medicine
John WhiteheadAnne Whitehead

Abstract

Despite an enormous and growing statistical literature, formal procedures for dose-finding are only slowly being implemented in phase I clinical trials. Even in oncology and other life-threatening conditions in which a balance between efficacy and toxicity has to be struck, model-based approaches, such as the Continual Reassessment Method, have not been universally adopted. Two related concerns have limited the adoption of the new methods. One relates to doubts about the appropriateness of models assumed to link the risk of toxicity to dose, and the other is the difficulty of communicating the nature of the process to clinical investigators responsible for early phase studies. In this paper, we adopt a new Bayesian approach involving a simple model assuming only monotonicity in the dose-toxicity relationship. The parameters that define the model have immediate and simple interpretation. The approach can be applied automatically, and we present a simulation investigation of its properties when it is. More importantly, it can be used in a transparent fashion as one element in the expert consideration of what dose to administer to the next patient or group of patients. The procedure serves to summarize the opinions and the data co...Continue Reading

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Citations

Jan 10, 2013·Cancer Chemotherapy and Pharmacology·Thomas JakiChristopher J Weir
Jan 30, 2015·Statistics in Medicine·Adrian P Mander, Michael J Sweeting
May 20, 2014·Journal of Biopharmaceutical Statistics·David Ohlssen, Amy Racine
Nov 12, 2013·International Journal of Stroke : Official Journal of the International Stroke Society·F C GoldieUNKNOWN VISTA Collaboration
May 29, 2018·Biometrical Journal. Biometrische Zeitschrift·Jose L JimenezMauro Gasparini
Sep 30, 2010·Nature Reviews. Rheumatology·Tsutomu Takeuchi, Hideto Kameda
Jul 17, 2020·Statistical Methods in Medical Research·Xynthia KavelaarsMaurits Kaptein
Mar 4, 2017·Journal of the Royal Statistical Society. Series C, Applied Statistics·Peter F ThallRalph G Zinner
Mar 9, 2021·Contemporary Clinical Trials Communications·Ami Takahashi, Taiji Suzuki
Jan 1, 2010·Statistical Science : a Review Journal of the Institute of Mathematical Statistics·John O'Quigley, Mark Conaway

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