R-TPI: rolling toxicity probability interval design to shorten the duration and maintain safety of phase I trials

摘要

To shorten trial duration and improve safety of Phase I trials, we propose R-TPI, a rolling enrollment design that combines the features in model-based designs such as mTPI-2 and rule-based designs such as rolling six. R-TPI employs a novel rolling enrollment scheme, which allows concurrent patient enrollment that is faster than cohort-based enrollment. Bench-marking against rolling six, we find that the R-TPI design is as fast in completing clinical trials but with fewer toxicity events and higher chance of finding the maximum tolerated dose (MTD) in the single scenario laid out in the 2008 rolling six publication. We also find that in a broad setting involving multiple scenarios, R-TPI is generally faster, safer, and more reliable than standard designs. R-TPI is a general design that can be applied to adult and pediatric Phase I trials. It reduces the length of trial duration, leads to safer trials with fewer toxicity events, and maintains relatively a high chance of identifying the MTD.