Phase 1 Clinical Trial Designs Explained: BOIN, CRM, BLRM & Modern Adaptive Strategies

By Kurt Preugschat

Phase 1 trials set the foundation for successful drug development, and the choice of design directly influences patient safety, development speed, and the quality of early data. While the traditional 3+3 design long dominated oncology trials, modern model-based and model-assisted designs now offer more precise, efficient, and flexible approaches to dose-finding.

This guide explores key methodologies and their optimal applications. The Bayesian Optimal Interval (BOIN) design balances rigor and accessibility, making it attractive for sites newer to adaptive methods. Variants of the classic approach, such as i3+3 and backfill designs, enhance safety while preserving familiar structures for organizations transitioning from conventional escalation. Model-based strategies deliver statistical precision and operational flexibility, particularly valuable in programs exploring novel mechanisms, combination therapies, or leveraging prior data.

Find out how you can select the right design by weighing statistical expertise, preclinical insights, regulatory considerations, and implementation complexity. With tailored guidance, sponsors can align design choices to program goals, accelerating progress while safeguarding patients.