Noninferiority studies

Nathan N, Borel T, Djibo A, Evans D, Djibo S, Corty JE et al. Ceftriaxone as effective as long-acting chloramphenicol in short-course heatment of meningococcal meningitis during epidemics a randomised noninferiority study. Lancet 2005 366(9482) 308-13. 

Paromomycin sulfate is an aminoglycoside antibiotic that until recently was used in parasitology only for oral therapy of intestinal parasitic infections (see previous text). It has recently been developed for the treatment of visceral leishmaniasis. A phase 3 trial in India showed excellent efficacy for this disease, with a daily intramuscular dosage of 11 mg/kg for 21 days yielding a 95% cure rate, and noninferiority compared with amphotericin. The drug was registered for the treatment of visceral leishmaniasis in India in 2006. In initial studies, paromomycin was well tolerated, with common mild injection pain, uncommon ototoxicity and reversible liver enzyme elevations, and no nephrotoxicity. Paromomycin is much less expensive than liposomal amphotericin or miltefosine, the other promising new therapies for visceral leishmaniasis. 

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. 

There is also a CONSORT statement concerning the reporting of cluster randomized trials (recall Section 5.6.2). The added complexities of these studies mean that reporting guidance specifically for these trials is appropriate (see Campbell et al., 2004). Additionally, the CONSORT group has published a statement on reporting equivalence and noninferiority randomized trials (see Piaggio et al., 2006). 

Bernard P, Chosidow O, Vaillant L French Erysipelas Study Group. Oral pristiuamycin versus standard penicillin regimen to treat erysipelas in adults randomised, noninferiority, open trial. BMJ 2002 325(7369) 864. 

The research question for a noninferiority trial is stated as Is the test drug not inferior to the control The null hypothesis to be tested in this study is ... 

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