On Bayesian Sequential Clinical Trial Designs

Clinical trials usually involve sequential patient entry. When designing a clinical trial, it is often desirable to include a provision for interim analyses of accumulating data with the potential for stopping the trial early. We review Bayesian sequential clinical trial designs based on posterior probabilities, posterior predictive probabilities, and decision-theoretic frameworks. A pertinent question is whether Bayesian sequential designs need to be adjusted for the planning of interim analyses. We answer this question from three perspectives: a frequentist-oriented perspective, a calibrated Bayesian perspective, and a subjective Bayesian perspective. We also provide new insights into the likelihood principle, which is commonly tied with statistical inference and decision making in sequential clinical trials. Some theoretical results are derived, and numerical studies are conducted to illustrate and assess these designs

The Ci3+3 Design for Dual-Agent Combination Dose-Finding Clinical Trials

We propose a rule-based statistical design for combination dose-finding trials with two agents. The Ci3+3 design is an extension of the i3+3 design with simple decision rules comparing the observed toxicity rates and equivalence intervals that define the maximum tolerated dose combination. Ci3+3 consists of two stages to allow fast and efficient exploration of the dose-combination space. Statistical inference is restricted to a beta-binomial model for dose evaluation, and the entire design is built upon a set of fixed rules. We show via simulation studies that the Ci3+3 design exhibits similar and comparable operating characteristics to more complex designs utilizing model-based inferences. We believe that the Ci3+3 design may provide an alternative choice to help simplify the design and conduct of combination dose-finding trials in practice

Optimal control-based inverse determination of electrode distribution for electroosmotic micromixer

This paper presents an optimal control-based inverse method used to determine the distribution of the electrodes for the electroosmotic micromixers with external driven flow from the inlet. Based on the optimal control method, one Dirichlet boundary control problem is constructed to inversely find the optimal distribution of the electrodes on the sidewalls of electroosmotic micromixers and achieve the acceptable mixing performance. After solving the boundary control problem, the step-shaped distribution of the external electric potential imposed on the sidewalls can be obtained and the distribution of electrodes can be inversely determined according to the obtained external electric potential. Numerical results are also provided to demonstrate the effectivity of the proposed method