The Cytel blog keeps you up to speed with the latest developments in biostatistics and clinical biometrics.
Traditional rule-based approaches to dose escalation such as 3+3 are widely used in early clinical development. They can be appealing due to the simplicity of execution. However, estimates produced may be highly variable and the targeting of true Maximum Tolerated Dose may be poor. Bayesian dose escalation approaches in early phase trials can offer an effective alternative to determining the maximum tolerable dose of a new drug more quickly, as well as ensuring that all of the information available to trial clinicians is taken into account so that the patients enrolled in the trial receive the best possible treatment.
If you’re in the practice of conducting early phase clinical trials, you’ve probably heard that modern trial designs include a number of new methodologies. There’s CRM and BLRM, model-based methods versus rule-based methods, and a number of other developments that might affect your clinical strategy. Each of these methods affects operational, financial and regulatory objectives in unique ways.
As a part of this year’s Joint Statistical Meeting, Cytel statisticians created a primer to go along with a workshop for early phase clinical trial design.
In the primer you will find:
- 1. An overview of 3+3, CRM, BLRM and mTPI methods
- 2. A synopsis of basic concepts like Bayesian and frequentist statistics, models and rules, etc.
- 3. Reflections on regulatory considerations
- 4. Case studies and topical exercises with Cytel’s high-powered simulations
- 5. A solution guide for those with access to Cytel's East software
Click to download the Primer
Use of the continual reassessment method (CRM) is safe, efficient, and flexible, according to a comprehensive review of 53 published Phase I trials from 2003-2013. The review, just published in the Journal of Clinical Oncology by leading researchers Iasonas and O'Quigley, challenges common misconceptions about model-based dose escalation designs.