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.
FDA draft guidance on “Co development of two or more unmarketed investigational drugs for use in combination” notes that:
“Combination therapy is an important treatment modality in many disease settings, including cancer, cardio-vascular disease, and infectious diseases. Recent scientific advances have increased our understanding of the pathophysiological processes that underlie these and other complex diseases. This increased understanding has provided further impetus for new therapeutic approaches using combinations of drugs directed at multiple therapeutic targets to improve treatment response or minimize development of resistance.” In this setting, it’s important to be able to design dose escalation studies which can identify the synergistic activity of compounds, and less toxic combinations.
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