Planning a dose-response study with subject-specific doses
This article is concerned with a dose-response study where the doses are subject-specific. The motivating example is a study on the use of radioiodine in metastatic thyroid cancer where the dose is individualized for each subject based on pharmacokinetic models of clearance of the agent. The goal is to design a study that will estimate the probability of response within a specified precision. This setup does not fit into well-studied dose-response designs primarily because doses are subject-specific. Here the dose-response relationship is modeled using logistic regression and a second-order approximation to the asymptotic variance of the model parameters is developed. The resulting procedure is simple to apply and requires minimal assumptions regarding the distribution of the dose levels. Simulation studies establish that, for a reasonable range of parameter values, the approximation is reasonably accurate. A Monte Carlo procedure is developed as well for cases when the approximation performs poorly. The proposed method is applied to the thyroid cancer study, including elicitation of parameters and a sensitivity analysis. Computer code in SAS and R are provided in the appendix.
Mithat Gonen. "Planning a dose-response study with subject-specific doses" Statistics in Medicine 24 (2005): 2613-2623.