Model Based vs. Rule Based Designs in Phase I Dose Finding Clinical Trials

Yunfei Wang and Jichuan Wang*

Model Based vs. Rule Based Designs in Phase I Dose Finding Clinical Trials. A phase I clinical trial is needed when a new drug or treatment is first used in human subjects. For ethnic reason, in such a trial, we have to carefully balance the possible benefit and harm so that the benefit.

The widely used rule-based design is the 3+3 design whereas the most referenced model based design is Continuous Reassessment Method. It follows an up and down algorithm or a random walk rule according to which we choose dose adaptively based on toxicity. Namely, if the toxicity in current dose is too toxic, we lower the dose if no unacceptable toxicity occurs in current dose, we can choose stay on the current dose or escalate to a higher dose. Lin and Shih3 extend the 3+3 design to a generalized form called A+B designs where A and B can be other numbers other than three. Other rule based designs following the same up and down algorithm are based on other statistics.

For example, an isotonic design bases on isotonic estimate of toxicity instead of raw toxicity with assumption that the toxicity increases with dose increasing. A t-statistics design bases on t-statistics whereas modified Toxicity Probability Design bases on toxicity probability interval. Interested in using the model based designs in their Phase I clinical trials if an easy to use software is available for application of CRM. Although interactive adaptive designs for Phase I clinical trials have been in software.

Clin Trial Pract Open J. 2016; 1(1): e1-e2. doi: 10.17140/CTPOJ-1-e001