Non-Inferiority Designs Comparing Placebo to a Proven Therapy for Childhood Pneumonia in Low Resource Settings

• Activity Number: 529 - Contributed Poster Presentations: WNAR
• Type: Contributed
• Date/Time: Wednesday, July 31, 2019 : 10:30 AM to 12:20 PM
• Sponsor: WNAR
• Author(s): Susanne May* and Siobhan Brown and Robert Schmicker and Scott Emerson and Evangelyn Nkwopara and Amy Ginsburg
• Companies: University of Washington and University of Washington and University of Washington and University of Washington and Save the Children and Save the Children
• Keywords: Placebo; sidedness; pneumonia; antibiotics; non-inferiority; infectious diseases

Abstract

After a new treatment is recommended to be first-line treatment for a specific indication, outcome and population, it may be unethical to use placebo as a comparator in trials for that setting. Nevertheless, in specific circumstances, use of a placebo group might be warranted, for example when it is believed that an active treatment may not be efficacious or cost-effective for a specific subpopulation. An example is antibiotic treatment for pneumonia, which may not be effective for many patients taking it due to the emergence of antibiotic-resistant strains or the high prevalence of viral and low prevalence of bacterial pneumonia. We explore the applicability of different design options in cases where the benefit of an established treatment is questioned, with particular emphasis on issues that arise in a low resource setting. Using the example of a clinical trial comparing the effectiveness of amoxicillin versus placebo in treating children two to 59 months of age with fast breathing pneumonia in Lilongwe, Malawi, we discuss the pros and cons of superiority versus non-inferiority designs, an intent-to-treat versus as-treated analysis, and the use and interpretation of one- versus