Fidaxomicin, ARR and NNT

Clostridium difficile endospores

The NEJM recently published a prospective, multicenter trial comparing fidaxomicin and oral vancomycin for the treatment of C. difficile diarrhea.  Fidaxomicin is a newly approved bacteriocidal antibiotic which works by interfering with RNA synthesis.  The hypothetical advantages of fidamoxicin are that it has a narrower spectrum and may reduce the incidence of recurrent C. diff. diarrhea.  The trial analyzed rates of clinical cure and recurrence of C. diff., and met the pre-established criteria for non-inferiority.  It also seemed to show a significant difference in rates of recurrent infection between the fidaxomicin and vancomycin groups, with an absolute risk reduction in the fidaxomicin group of 9.9% in the modified intention-to-treat analysis and 10.7% in the per-protocol analysis.

The absolute risk reduction (ARR) is simply the experimental event rate (EER) minus the control event rate (CER), which in this case is the incidence of recurrent C. diff. infection in the fidaxomicin group minus the incidence of recurrent C. diff. infection in the vancomycin group.  The ARR is a really useful number, because it allows you to calculate the number needed to treat (NNT), which is just 1/ARR.  In this case, if we split the difference between the intention-to-treat and the per-protocol analyses and guess that the ARR is really about 10%, that means the NNT to prevent one case of recurrent C. diff diarrhea is equal to 1/0.1, or 10.  This is significant, but enthusiasm should be tempered by the fact that this is a new drug, and by the fact that whereas a 10 day course of oral vancomycin costs $100 (if you use IV vancomycin given orally instead of the more expensive Vancocin™ pulvules) a ten-day course of fidaxomicin costs about $2200.  Additionally, the study was heavily funded by Optimer pharmaceuticals, which makes the drug, and many of the investigators had received honoraria and other payments from Optimer.