February 24, 2019

PITE

Probability Interval Design based on both Toxicity and Efficacy


The Probability Interval design based on both Toxicity and Efficacy (PITE) provides an efficient and powerful solution to immuno-oncology (IO) phase 1 dose finding trials. As the monotonic dose-response assumption, which is applicable for cytotoxic drugs, may not hold for IO agents, traditional phase 1 dose finding designs searching for the maximum tolerated dose (MTD) are not suitable to IO agents. PITE is a novel and transparent interval design for dose finding trials of IO agents. This design incorporates efficacy outcomes to inform dosing decisions to optimize efficacy and safety simultaneously. PITE is a perfect match to the CAR-T agents and other potential IO agents, in which the efficacy outcome (or the surrogate efficacy outcome) can be quickly observed.

Benefits

  1. Compared to the toxicity-based designs (3+3, CRM, mTPI-2, etc.), PITE incorporates information of efficacy and therefore enables investigator to quickly assess the drug’s potency and look for the optimal biological dose (OBD), rather than MTD.
  2. PITE is simple, flexible and transparent, as the decision table can be pre-tabulated prior to trial initiation.