Confidence intervals for non-inferiority

For non-inferiority, the first step involves defining a non-inferiority margin. Suppose that we are developing a new treatment for hypertension and potentially the reason why the new treatment is better is that it has fewer side effects, although we are not anticipating any improvement in terms of efficacy. Indeed, suppose that we are prepared to pay a small price for a reduction in the side effects profile say up to 2 mmHg in the mean reduction in diastolic blood pressure. 

8 mmHg) then non-inferiority would not have been established since the lower end of that confidence interval falls below —2 mmHg. Note again that there is no mention of conventional p-values, they have no part to play in non-inferiority. 

In order to demonstrate non-inferiority, it is only one end of the confidence interval that matters in our example it is simply the lower end that needs to be above —2 mmHg. It is therefore not really necessary to calculate the upper end of the interval and sometimes we leave this unspecified. The resulting confidence interval with just the lower end is called a one-sided 97.5per cent confidence interval the two-sided 95 per cent confidence interval cuts off 2.5 per cent at each of the lower and upper ends, having the upper end undefined leaves just 2.5 per cent cut off at the lower end. The whole of this confidence interval must be entirely to the right of the non-inferiority margin for non-inferiority to be established. 

ICH E9 (1998) Note for Guidance on Statistical Pn ndples for Clinical Trials  

Example 12.1 Fluconazole compared to amphotericin B in preventing relapse in cryptococcal meningitis 

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