Phase I Clinical Trial Designs: Continuous Reassessment Method (CRM)

By Kurt Preugschat

Phase I trials lay the groundwork for drug development by determining safe and effective dosing. Although the traditional 3+3 design has long been the standard for dose escalation, the Continuous Reassessment Method (CRM) introduces a more flexible, data-driven alternative. Leveraging Bayesian modeling, CRM adjusts dose recommendations in real time based on observed toxicities, enhancing patient safety while accelerating the identification of the maximum tolerated dose.

Since its introduction in 1990, CRM has proven more accurate than rule-based designs, yet adoption has been slow due to training gaps, resource demands, and regulatory hurdles. Recent advances in software and statistical tools, however, are making implementation more accessible. CRM is gaining traction in oncology, cell therapy, and biologics, and with growing evidence, evolving tools, and potential AI integration on the horizon, it is poised to reshape early-phase research.