Phase I clinical trials are often subject to severe limitations. The most important one is that they usually allow only for binary response—toxic (1) or non-toxic (0)—rather than a range of responses from 0 to 1. They also may not allow a new patient to be treated until results for all previous patients are available. They may assign patients to doses in groups of two or more, rather than individually. They may require the selected dose to be one of a few pre-specified doses. The method proposed here addresses these limitations. The model uses a logistic dose-response curve with two parameters for the mean response. The response at any dose follows a beta distribution, which entails a third parameter. The choice of dose for a patient is based on a utility function that reflects the latest estimates of toxicity and of the variance of the estimate of the maximum tolerated dose (MTD). Simulations show that the method works well, and that a non-binary toxicity measure leads to a far more accurate MTD estimate than does a binary one.
Biostatistics | Clinical Trials
Potthoff, Richard F. and George, Stephen L., "Phase I Clinical Trials With Non-Binary Toxicity Response" (May 2007). Duke Biostatistics and Bioinformatics (B&B) Working Paper Series. Working Paper 3.