Simple benchmark for planning and evaluating complex dose finding designs

• Activity Number: 429
• Type: Invited
• Date/Time: Wednesday, August 6, 2014 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Ken Cheung*+
• Companies: Columbia University
• Keywords: Sample size calculation ; Reproducible method

Abstract

Modern dose finding studies and designs are highly specific to individual clinical settings. In addition, as outcome-adaptive methods often involve complex algorithms, it is crucial to have diagnostic tools at the planning stage to evaluate the plausibility of a specific method's simulated performance and the adequacy of the algorithm. In this talk, I will introduce a simple technique that provides an upper limit, or a benchmark, of accuracy for dose finding methods for a given design objective. The proposed benchmark is nonparametric optimal, and is demonstrated by examples to be a practical accuracy upper bound for model-based dose finding methods. We illustrate the implementation of the technique in the context of phase I trials that consider multiple toxicities and phase I/II trials where dosing decisions are based on both toxicity and efficacy, and apply the benchmark to several clinical examples considered in the literature. By comparing the operating characteristics of a dose finding method to that of the benchmark, we can form quick initial assessments of whether the method is adequately calibrated and evaluate its sensitivity to the dose-outcome relationships.