April 27, 2010
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.
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. Possibly one other reason is the diffi culty of doing a lot better. In this essay we look at using the oft touted alternative to the 3+3, the Continuous Reassessment Method (CRM) proposed by O’Quigley in 1990 and given some modest but important design tweaks by Goodman in 1995.
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Tom Parke
Tom Parke is head of clinical trial solutions at Tessella and has been working at Tessella for over ten years. For a large part of that time he has been working on Adaptive Clinical Trial projects particularly with Dr Mike Krams and Don and Scott Berry at Berry Consultants.
Tom has helped implement numerous adaptive phase 2 dose finding trials that are now complete, for a range of pharmaceutical companies across a range of indications. For these trials, he managed the development of simulation tools, systems to support the running of the trials and the integration of adaptive algorithms with existing IVRS and EDC systems.
He is currently working on his 12th adaptive dose finding trial, and consulting with a number of companies to help them define the software systems they require to move adaptive clinical trials into their mainstream activities. Before working at Tessella, Tom had worked at Praxis (part of Deloitte & Touche) most notably managing projects for part of the air traffic control system at Heathrow Airport, and control software for imaging systems for GE Medical Systems and Varian Oncology.
