LAUSR

There are many design options for toxicity-driven phase 1 dose-finding in oncology drug development. There are methods that are simple, traditional and transparent, such as the 3 + 3 1 or rolling 6 design 2 that do not target a dose limiting toxicity (DLT)-rate and are focused on exploring escalating doses subject to limits on patient risk. On the other end of the spectrum are designs that focus on a DLT target-rate and require sophisticated tools throughout the conduct of the study, are less transparent, and require statistical support. Two examples are the CRM design 3,4 and the BLRM design. 5 There are also designs between these two extremes. Closest to the 3 + 3 and rolling 6 are queue-based variations of those designs 6 or other A + B designs 7 that also explore doses subject to pre-specified rules to limit patient risk. Closer to the CRM or BLRM are statistically motivated methods such as the mTPI, 8 TEQR, 9 and BOIN, 10 where there is a target DLT rate and/or range, but simple decision rules and tables reduce the absolute requirement for sophisticated tools or a statistician except in the design and final analysis.