Noninferiority studies, clinical trials

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. 

Chlorinated polyethylene elastomer (CPE) is one of the alternatives of the PDMS. Extraoral maxillofacial prostheses have been fabricated with silicone elastomer for 50 years, with few improvements. A controlled, randomized, prospective, double-blind, single-crossover, multicenter, phase 111 clinical trial was performed by Kiat-Amnuay et al. to determine the noninferiority of CPE to silicone elastomer [46]. For this purpose, 42 patients were randomly assigned to wear a custom-made prosthesis fabricated from both materials for four months and asked to rate their satisfaction (0 = not satisfied, 10 = completely satisfied). Of the 28 patients who completed the study, 68% had used silicone prostheses previously. Overall, patients rated the silicone prosthesis higher than CPE (difference 2.2, 95% confidence interval [Cl] 0.9 to 3.6, P =. 017). Previous users had a stronger preference for silicone (difference 3.3, 95% Cl 1.7 to 4.9, P =... 

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. 

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