• Sarah Zohar, Matthieu Resche-Rigon, and Sylvie Chevret.
• INSERM U717, Département de Biostatistique et Informatique Médicale, Hôpital Saint-Louis, Paris 7 University, France. sarah.zohar@univ-paris-diderot.fr
• Clin Trials. 2013 Jan 1; 10 (3): 414-21.

BackgroundThe Continual Reassessment Method typically is presented as the method of choice for the purpose of dose-finding based on a toxicity scale in phase I clinical trials. However, this adaptive statistical approach also can be applied easily to dose-finding experiments in phase II trials.PurposeTo provide a case study from a real clinical trial to illustrate the use of the Continual Reassessment Method in the context of phase II dose finding.MethodsThe Continual Reassessment Method was used to model the dose-failure relationship in order to estimate the minimal effective dose. This approach was retrospectively used to determine the minimal effective dose of granulocyte colony-stimulating factor for peripheral blood stem cell collection in allografted patients following chemotherapy.ResultsAfter the inclusion of 25 patients, the minimal effective dose was estimated to be the third dose level tested in the study.LimitationsThe main limitation of the Continual Reassessment Method, which is not specific to the method but to the dose-finding setting, is that the empirical choice of the dose range can be either under or over-estimated. The method requires a calibration study prior to trial onset.ConclusionsAssuming that a dose-effect relationship is monotonically increasing, the use of the Continual Reassessment Method in phase II dose-finding studies allows the estimation of the minimum effective dose for further studies. Modeling the dose-failure relationship allows the direct use of available software developed for the Continual Reassessment Method in the context of phase I clinical trials.

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