Optimal design problems for the bivariate Emax model
(English)Manuscript (preprint) (Other academic)
Finding a suitable dose is among the most difficult tasks during clinical development of a new drug. In early phases dose finding studies usually focus on finding a safe dose. Safety variables are thus of main interest. In later phases the focus is shifted towards efficacy. Typically a primary efficacy variable is defined and modeled. Various dose-response models have been suggested. For continuous responses among the most successful ones is the Emax model. Here both efficacy and safety are considered simultaneously and the Emax model is extended to a model with a bivariate response, one response being a primary efficacy variable and one being a primary safety variable. This model is referred to as the bivariate Emax model. The focus is on locally c-optimal designs for the bivariate Emax model and a simplified version of it. More specifically the locallyc-optimal designs minimize the asymptotic variance for the estimate of the dose that maximizes the patient's utility. The utility is a function of the efficacy and safety variables and referred to as the Clinical Utility Index (CUI).
bivariate Emax model, Clinical Utility Index (CUI), c-optimal design, dose-response studies
Probability Theory and Statistics
Research subject Statistics
IdentifiersURN: urn:nbn:se:su:diva-102867OAI: oai:DiVA.org:su-102867DiVA: diva2:713850