title: Rotavirus vaccine effectiveness in low-income settings: An evaluation of the test-negative design.
abstract: The test-negative design (TND), an epidemiologic method currently used to measure rotavirus vaccine (RV) effectiveness, compares the vaccination status of rotavirus-positive cases and rotavirus-negative controls meeting a pre-defined case definition for acute gastroenteritis. Despite the use of this study design in low-income settings, the TND has not been evaluated to measure rotavirus vaccine effectiveness.
  
  
  
  This study builds upon prior methods to evaluate the use of the TND for influenza vaccine using a randomized controlled clinical trial database. Test-negative vaccine effectiveness (VE-TND) estimates were derived from three large randomized placebo-controlled trials (RCTs) of monovalent (RV1) and pentavalent (RV5) rotavirus vaccines in sub-Saharan Africa and Asia. Derived VE-TND estimates were compared to the original RCT vaccine efficacy estimates (VE-RCTs). The core assumption of the TND (i.e., rotavirus vaccine has no effect on rotavirus-negative diarrhea) was also assessed.
  
  
  
  TND vaccine effectiveness estimates were nearly equivalent to original RCT vaccine efficacy estimates. Neither RV had a substantial effect on rotavirus-negative diarrhea.
  
  
  
  This study supports the TND as an appropriate epidemiologic study design to measure rotavirus vaccine effectiveness in low-income settings.
authors.affiliation: Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, United States; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States. Electronic address: laurenms@uw.edu.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Schwartz
authors.affiliation: Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, United States; Department of Biostatistics, School of Public Health, University of Washington, Seattle, WA, United States; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States; Center for Inference and Dynamics of Infectious Diseases, Seattle, WA, United States.
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Halloran
authors.affiliation: Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, United States.
authors.forename: Ali
authors.initials: A
authors.lastname: Rowhani-Rahbar
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, United States.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Neuzil
authors.affiliation: Center for Vaccine Innovation and Access, PATH, Seattle, WA, United States.
authors.forename: John C
authors.initials: JC
authors.lastname: Victor
mesh_terms: D017954:Africa South of the Sahara / Q000453:epidemiology; D001208:Asia / Q000453:epidemiology; D004812:Epidemiologic Methods; D005260:Female; D005759:Gastroenteritis / Q000453:epidemiology* / Q000517:prevention & control*; D006801:Humans; D007223:Infant; D008297:Male; D016032:Randomized Controlled Trials as Topic; D012400:Rotavirus Infections / Q000453:epidemiology* / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D022243:Rotavirus Vaccines
keywords: Rotavirus; Test-negative design; Vaccine