Phase I (or phase II) dose-ranging clinical trials: proposal of a two-stage Bayesian design.
We propose a new design for phase I (or phase II) dose-ranging clinical trials aiming at determining a dose of an experimental treatment to satisfy safety (respectively efficacy) requirements, at treating a sufficiently large number of patients to estimate the toxicity (respectively failure) probability of the dose level with a given reliability, and at stopping the trial early if it is likely that no dose is safe (respectively efficacious). A two-stage design was derived from the Continual Reassessment Method (CRM), with implementation of Bayesian criteria to generate stopping rules. A simulation study was conducted to compare the operating characteristics of the proposed two-stage design to those reached by the traditional CRM. Finally, two applications to real data sets are provided.
Zohar
Sarah
S
Département de Biostatistique et Informatique Médicale, Hôpital Saint-Louis, AP-HP, Université Paris 7, Paris, France. szohar@chu-stlouis.fr
Chevret
Sylvie
S
D001499:Bayes Theorem; D017321:Clinical Trials, Phase I as Topic / Q000706:statistics & numerical data*; D017322:Clinical Trials, Phase II as Topic / Q000706:statistics & numerical data*; D004305:Dose-Response Relationship, Drug; D015340:Epidemiologic Research Design; D006801:Humans; D008874:Midazolam / Q000008:administration & dosage; D015233:Models, Statistical; D009010:Monte Carlo Method; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*
D004364:Pharmaceutical Preparations; D008874:Midazolam