Exciting news! Back in November, I posted a blog describing the results of the University of Pittsburgh placebo-controlled trial of antibiotic therapy of well-documented otitis media in children 6 months to two years of age. Those results were taken from clintrials.gov where the authors had posted their data. The latest issue of the New England Journal of Medicine carries two articles, one from the Pittsburgh group and the other from Finland describing placebo-controlled trials of antibiotics for otitis. Both show clearly that, when properly diagnosed, antibiotics work well in the treatment of otitis and that placebo does not. Of course, this is something that most parents knew anyway – but here it is in black and white.
In the Pittsburgh study of 291 young children, when looking just at resolution of symptoms, although antibiotics were better than placebo, the differences were small. The authors used a well-validated symptom score to follow progress. Here, antibiotic treatment was clearly superior. At the day 10-12 visit, only 23% of antibiotic treated patients had a symptom score >8 compared to 61% of placebo treated patients for a treatment effect of 38%. The effect was greatest among those children with the highest symptom score at baseline. When looking at failure, defined as persistence of signs of infection on exam, the differences were also striking. The greatest difference occurred at day 10-12 where the failure rate among placebo-treated patients was 51% compared to 16% among antibiotic treated patients – a 35% treatment effect. One placebo treated child suffered mastoiditis.
In the Finnish study of children aged 6-35 months, quoting directly from the article,
The primary outcome was the time to treatment
failure, which was a composite outcome consisting
of six independent components: no improvement
in overall condition by the first scheduled
visit (day 3) (i.e., unless parents thought that their
child’s overall condition was improving, the case
was categorized as treatment failure), a worsening
of the child’s overall condition at any time, no
improvement in otoscopic signs by the end-of treatment
visit on day 8 (see videos 4 through 8),
perforation of the tympanic membrane at any
time, severe infection (e.g., mastoiditis or pneumonia)
necessitating systemic open-label antimicrobial
treatment at any time, and any other reason
for stopping the study drug (e.g., an adverse
event or nonadherence to the study drug) at any time.
Overall, treatment failure occurred in an astounding 45% of patients receiving placebo compared to 19% of those receiving antibiotics – a 26% treatment effect. Five placebo patients and only one antibiotic treated patient suffered perforation of the eardrum. Antibiotics reduced the need for rescue therapy by over 80%. Antibiotic-treated children had shorter absences from school and their parents had shorter absences from work.
In an accompanying editorial, Dr. Jerome Klein posed and answered the question,
Is acute otitis media a treatable disease? The investigators in
Pittsburgh and Turku have provided the best data
yet to answer the question, and the answer is yes;
more young children with a certain diagnosis of
acute otitis media recover more quickly when
they are treated with an appropriate antimicrobial agent.
I hope these studies put to rest the unreasonable requirement both in the US and in Europe for placebo controlled trials of antibiotics for marketing approval. The studies published in the New England Journal should be the last such placebo controlled trials of well-documented otitis that we should perform.
No comments:
Post a Comment