Compound designs for dose-finding in the presence of nondesignable covariates.

Compound optimal designs are considered where one component of the design criterion is a traditional optimality criterion such as the D-optimality criterion, and the other component accounts for higher efficacy with low toxicity. With reference to the dose-finding problem, we suggest the technique to choose weights for the two components that makes the optimization problem simpler than the traditional penalized design. We allow general bivariate responses for efficacy and toxicity. We then extend the procedure in the presence of nondesignable covariates such as age, sex, or other health conditions. A new breast cancer treatment is considered to illustrate the procedures.