We have located links that may give you full text access.
COMPARATIVE STUDY
JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
The continual reassessment method: comparison of Bayesian stopping rules for dose-ranging studies.
Statistics in Medicine 2001 October 16
The continual reassessment method (CRM) provides a Bayesian estimation of the maximum tolerated dose (MTD) in phase I clinical trials and is also used to estimate the minimal efficacy dose (MED) in phase II clinical trials. In this paper we propose Bayesian stopping rules for the CRM, based on either posterior or predictive probability distributions that can be applied sequentially during the trial. These rules aim at early detection of either the mis-choice of dose range or a prefixed gain in the point estimate or accuracy of estimated probability of response associated with the MTD (or MED). They were compared through a simulation study under six situations that could represent the underlying unknown dose-response (either toxicity or failure) relationship, in terms of sample size, probability of correct selection and bias of the response probability associated to the MTD (or MED). Our results show that the stopping rules act correctly, with early stopping by using the two first rules based on the posterior distribution when the actual underlying dose-response relationship is far from that initially supposed, while the rules based on predictive gain functions provide a discontinuation of inclusions whatever the actual dose-response curve after 20 patients on average, that is, depending mostly on the accumulated data. The stopping rules were then applied to a data set from a dose-ranging phase II clinical trial aiming at estimating the MED dose of midazolam in the sedation of infants during cardiac catheterization. All these findings suggest the early use of the two first rules to detect a mis-choice of dose range, while they confirm the requirement of including at least 20 patients at the same dose to reach an accurate estimate of MTD (MED). A two-stage design is under study.
Full text links
Related Resources
Trending Papers
Heart failure with preserved ejection fraction: diagnosis, risk assessment, and treatment.Clinical Research in Cardiology : Official Journal of the German Cardiac Society 2024 April 12
Proximal versus distal diuretics in congestive heart failure.Nephrology, Dialysis, Transplantation 2024 Februrary 30
Efficacy and safety of pharmacotherapy in chronic insomnia: A review of clinical guidelines and case reports.Mental Health Clinician 2023 October
World Health Organization and International Consensus Classification of eosinophilic disorders: 2024 update on diagnosis, risk stratification, and management.American Journal of Hematology 2024 March 30
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app