The principal aim of an Oncology phase 1 trial is the identification of the Maximum Tolerated Dose (MTD). The majority of oncology phase 1 trials are run using a design called “3+3”. Under this design, subjects are treated in cohorts of 3, and based on the number of dose limiting toxicities seen in that cohort, decisions on which dose to give the next cohort and whether to stop the trial are made.
In , Reiner at al argue that this design does not give very good operating characteristics. “the probability of recommending the [correct] MTD at the end of the trial ... never exceeds 44% and is most often closer to 30%”. Despite this, the 3+3 design remains in common usage due to its simplicity, the straightforward (and appealing) nature of its decision rules and its familiarity.