This module focuses on the statistical issues that must be addressed in the design, implementation, and reporting of randomized clinical trials. This module presumes the student has familiarity with the topics covered in Module 1: Introduction to Clinical Trials.

The premise of the module is that each clinical trial poses unique problems, and thus the best design for a particular clinical trial may not be appropriate for another. Hence, emphasis is placed on the iterative approach of considering alternative design structures, selecting candidate designs, evaluating the operating characteristics of those designs with respect to a variety of criteria, and comparing a number of designs to find an acceptable design for the scientific problem at hand. It will include discussion of:

• Alternative randomization strategies: randomization ratios, stratification, covariate adaptive randomization, response adaptive randomization;
• Choice of statistical analysis models: choice of statistic, covariate adjustment;
• Sequential adaptive designs: fixed sample, group sequential, blinded sample size re-estimation, unblinded sample size re-estimation, adaptive enrichment;
• Overview of approaches to missing data: sensitivity to missing not at random, and
• Analysis including covariate adaptive and response adaptive randomization.

The module concludes with a discussion of the ways that the complete design and its operating characteristics might be summarized in the study protocol and fully documented in a statistical analysis plan (SAP) in order to satisfy study investigators and regulatory agencies.