Factorial dose-response studies using frequency and magnitude of dose

In the early stages of traditional drug development, the frequency of dosing (e.g., QD, BID, etc.) is typically determined by the pharmacokinetic properties of a compound. After an appropriate dose frequency is chosen, the magnitude of dose is then evaluated via parallel-group dose-response trials. For some drugs, however, blood levels at any given time may not be accurate predictors of clinical response, or the drug may not be absorbed systemically. In those instances, we propose the use of a factorial dose-response trial that simultaneously evaluates frequency of dosing and magnitude of dose. We consider this approach to selecting an appropriate dosing regimen to be more scientifically founded and more cost-effective, than independent evaluation of dose and frequency through separate clinical trials. Some design considerations and statistical analysis strategies for these factorial trials are presented in this paper.