AFP Journal Club casts doubt on NEJM study

Do children younger than 2 years of age with acute otitis media (AOM) require antibiotics, or is a watchful waiting approach just as effective? A study designed to answer this question was published last year in the New England Journal of Medicine and concluded that a 10-day course of amoxicillin-clavulanate "tended to reduce the time to resolution of symptoms and reduced the overall symptom burden and the rate of persistent signs of acute infection on otoscopic examination." However, an analysis of this study by Drs. Andrea Darby-Stewart, Mark Graber, and Robert Dachs in the November 15, 2011 AFP Journal Club concluded that the results actually supported a watchful waiting strategy because the primary outcome (likelihood of treatment failure) was disease-oriented rather than patient-oriented:

The only clinically significant outcome was likelihood of treatment failure; yet, this was defined as the presence of any symptom of AOM and persistent otoscopic signs of AOM on day 10 to 12. Treatment did not fail in any children based on symptoms alone—all treatment failures were defined by persistent inflammation on examination. The treatment failed even if the patient was symptomatically better. Most of these asymptomatic children likely would never have presented for follow-up in routine practice. And, only four to six children had to be treated to cause diarrhea, rash, or diaper dermatitis.

The January 15th AFP Journal Club continues this story by reporting an apparent discrepancy between the predesignated primary outcomes in study's original protocol (published on ClinicalTrials.gov and posted to the NEJM's website) and those that were ultimately reported in the study abstract's conclusions:

There were only three primary outcomes planned and the fourth outcome, otoscopic resolution, was one of many planned secondary outcomes. ... What is even more concerning is that the otoscopic findings are only one of 22 secondary outcomes evaluated in this study. It amazes me that a significant number of these findings, the ones that just happen to support placebo, were never reported. The secondary outcomes that demonstrated no difference between placebo and amoxicillin/clavulanate were analgesia requirements in these children; number of needed follow-up visits to a primary care physician; number of visits to the emergency department; missed hours of work by the parents; and parental satisfaction. 

The bottom line: family physicians should not conclude that this NEJM study showed that antibiotics are superior to watchful waiting for acute otitis media in young children. In fact, by showing that only 6 children needed to be treated with antibiotics to cause one additional episode of diarrhea, it suggests that the opposite conclusion may be true.