Challenges in the Design of Antibiotic Equivalency Studies: The Multicenter Equivalency Study of Oral Amoxicillin versus Injectable Penicillin in Children Aged 3–59 Months with Severe Pneumonia

Tufts University, Бостон, Georgia, United States
Clinical Infectious Diseases (Impact Factor: 8.89). 09/2004; 39(4):526-31. DOI: 10.1086/422453
Source: PubMed


The World Health Organization (WHO) recommends that children with severe pneumonia (characterized by cough or difficult breathing,
as well as lower chest wall indrawing) be hospitalized and treated with parenteral penicillin. Oral amoxicillin, if equally
effective for treating severe pneumonia, would address challenges associated with providing parenteral therapy, including
risk of transmission of bloodborne pathogens from contaminated needles, exposure to nosocomial pathogens during hospitalization,
inadequate access to health care facilities, and cost. The recently completed multicenter international trial of oral amoxicillin
versus parenteral penicillin for treatment of severe pneumonia demonstrated the equivalency of these agents in children with
severe pneumonia. This article focuses on the challenges of designing an equivalence study and the threats to the validity
of the trial results, particularly the implications of the bias toward finding equivalence when subjects are unlikely to respond
to either study therapy. These considerations have implications for use of the Amoxicillin Penicillin Pneumonia International
Study (APPIS) results in clinical practice and for potential modification of WHO treatment guidelines.

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Available from: Archana B Patel, Jan 06, 2016
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    Preview · Article · Apr 2006 · Bulletin of the World Health Organisation
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