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

By Kurt Preugschat

Phase 1 trial design is a critical determinant of early drug development success, directly influencing dose identification, patient safety, and trial efficiency. While the traditional 3+3 design has long been the standard, modern model-based and model-assisted approaches now offer enhanced precision, operational flexibility, and statistical rigor.

Designs such as BOIN (Bayesian Optimal Interval) provide accessible yet robust frameworks for dose-finding, while i3+3 and its backfill variant improve safety assessment in targeted therapy studies. The mTPI-2 design balances simplicity and power, making it well-suited for immuno-oncology programs with complex dose-response relationships. For trials requiring precise dose optimization, the CRM (Continual Reassessment Method) enables rapid, statistically informed recommendations, and the BLRM (Bayesian Logistic Regression Model) leverages historical data and combination therapy insights to guide escalation safely.

Selecting the optimal Phase 1 design requires alignment with operational capacity, regulatory considerations, preclinical knowledge, and statistical expertise. As precision medicine evolves, trial designs must increasingly accommodate personalized therapies, adaptive strategies, and AI-driven modeling. Sponsors who integrate model-based and model-assisted designs early can enhance dose-finding accuracy, accelerate timelines, and strengthen regulatory confidence, ultimately improving patient outcomes while maximizing scientific and operational efficiency.