title: Multiple-Objective Optimal Designs for Studying the Dose Response Function and Interesting Dose Levels.
abstract: We construct an optimal design to simultaneously estimate three common interesting features in a dose-finding trial with possibly different emphasis on each feature. These features are (1) the shape of the dose-response curve, (2) the median effective dose and (3) the minimum effective dose level. A main difficulty of this task is that an optimal design for a single objective may not perform well for other objectives. There are optimal designs for dual objectives in the literature but we were unable to find optimal designs for 3 or more objectives to date with a concrete application. A reason for this is that the approach for finding a dual-objective optimal design does not work well for a 3 or more multiple-objective design problem. We propose a method for finding multiple-objective optimal designs that estimate the three features with user-specified higher efficiencies for the more important objectives. We use the flexible 4-parameter logistic model to illustrate the methodology but our approach is applicable to find multiple-objective optimal designs for other types of objectives and models. We also investigate robustness properties of multiple-objective optimal designs to mis-specification in the nominal parameter values and to a variation in the optimality criterion. We also provide computer code for generating tailor made multiple-objective optimal designs.
authors.forename: Seung Won
authors.initials: SW
authors.lastname: Hyun
authors.forename: Weng Kee
authors.initials: WK
authors.lastname: Wong
mesh_terms: D056808:Biostatistics; D002986:Clinical Trials as Topic / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D020714:Maximum Tolerated Dose; D015233:Models, Statistical; D012107:Research Design; D012680:Sensitivity and Specificity