Noninferiority trials study design

Phase III studies can be tested against a placebo control with the intent of showing superiority over placebo. Another type of study design is to show equivalence or noninferiority to an approved therapy. An equivalence trial is intended to show that the response to two or more treatments differs by an amount which is clinically unimportant. A noninferiority trial demonstrates that the response to the investigational product is not clinically inferior to a comparative agent. 

Group sequential designs, particularly in noninferiority safety studies where many events may occur after accrual during the follow-up phase, are unlikely to stop early. The design described here, instead, uses accruing information to predict how many events the current cohort is likely to provide with addition follow-up. Therefore, rather than having many patients with short exposure times, it relies on a smaller number of patients with greater exposure times—with that optimal number chosen adaptively and based upon internal trial data. 

This chapter introduces basic concepts in statistical analysis that are of relevance to describing and analyzing the data that are collected in clinical trials, the hallmark of new drug development. (Statistical analysis in nonclinical studies was addressed earlier in Chapter 4.) This chapter therefore sets the scene for more detailed discussion of the determination of statistical significance via the process of hypothesis testing in Chapter 7, evaluation of clinical significance via the calculation of confidence intervals in Chapter 8, and discussions of adaptive designs and of noninferiority/equivalence trials in Chapter 11. 

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