Trials 2017 Dec 28;18(1):620. Epub 2017 Dec 28.
CRUK MRC Oxford Institute for Radiation Oncology, Gray Laboratories, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.
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Comput Methods Programs Biomed 2015 Oct 16;121(3):189-96. Epub 2015 Jun 16.
Department of Biostatistics, University of Alabama at Birmingham, School of Public Health, 1665 University Blvd., Room 327, Birmingham, AL 35294-0022, USA.
Background And Objectives: Dose finding trials using model-based methods have the ability to handle the increasingly complex landscape being seen in clinical trials. Issues such as patient heterogeneity in trial populations are important to address in the designing of a trial in addition to the inclusion/exclusion criteria. Designs accommodating patient heterogeneity have been described using the continual reassessment method (CRM) and time-to-event CRM (TITE-CRM), yet, the implementation of these trials in practice have been limited. Read More
BMC Cancer 2018 02 5;18(1):133. Epub 2018 Feb 5.
Division of Translational Research & Applied Statistics, Department of Public Health Sciences, University of Virginia, P.O. Box 800717, Charlottesville, VA, USA.
Background: Broad implementation of model-based dose-finding methods, such as the continual reassessment method (CRM), has been limited, with traditional or modified 3 + 3 designs remaining in frequent use. Part of the reason is the lack of reliable, easy-to-use, and robust software tools for designing and implementing more efficient designs.
Results: With the aim of augmenting broader implementation of model-guided methods, we have developed a web application for the Bayesian CRM in the R programming language using the Shiny package. Read More
Br J Cancer 2017 Jul 29;117(3):332-339. Epub 2017 Jun 29.
Imperial Clinical Trials Unit, Imperial College London, Stadium House, 68 Wood Lane, London W12 7RH, UK.
Background: Dose-finding trials are essential to drug development as they establish recommended doses for later-phase testing. We aim to motivate wider use of model-based designs for dose finding, such as the continual reassessment method (CRM).
Methods: We carried out a literature review of dose-finding designs and conducted a survey to identify perceived barriers to their implementation. Read More
Clin Trials 2012 Jun 30;9(3):303-13. Epub 2012 Apr 30.
Division of Cancer Biostatistics, Markey Cancer Center, University of Kentucky, Lexington, USA.
Background: Various dose-finding clinical trial designs, including the continual reassessment method (CRM), dichotomize toxicity outcomes based on prespecified dose-limiting toxicity (DLT) criteria. This loss of toxicity information is particularly inefficient due to the small sample sizes in phase I trials, especially when Common Terminology Criteria for Adverse Events (CTCAE v4.0) are an established ordinal toxicity grading classification already used in the clinical practice. Read More