Clinical Trials

❘❙❚■ Chapter 14 | Noninferiority TrialsFigure 1. Examples of noninferiority study results.ZExampleYXW–10 –5 0 5 10 15Treatment differenceStudies W and Y show noninferiority; study X shows a lack of noninferiority; study Z shows superiority.principles underlying the drawing of conclusions will be the same. Some typicalnoninferiority study CIs are shown in Figure 1.Example (continued)The 95% CI for the difference in success rate (Augmentin SR 2000/125 mg –Augmentin 875/125 mg), calculated using the normal approximation to thebinomial distribution, is (–3.0%, 8.3%) (per-protocol [PP] population) (see Figure 1,study W). This lies entirely above the specified noninferiority limit of –10%,so the study demonstrates that Augmentin SR 2000/125 mg is noninferior toAugmentin 875/125 mg.Had the lower limit of the CI been below the noninferiority limit, then the studywould not have demonstrated noninferiority (see Figure 1, study X). Note thatlack of noninferiority does not necessarily imply inferiority, since the CI doesinclude some positive values for the treatment difference. The reverse is alsotrue (see Figure 1, study Y). These results would lead to a conclusion ofnoninferiority (since the CI lies above –10%), though they also show a statisticallysignificant (clinically insignificant) difference in favor of the standard therapy.Patient populationAnother key issue in analysis is the choice of patient population. The intention-totreat(ITT) principle is widely recognized as the most valid analytical approach forsuperiority trials that involve long-term follow-up, because it adheres to the138