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Am J Trop Med Hyg. 2015 Apr;92(4):744-51. doi: 10.4269/ajtmh.14-0518. Epub 2015 Feb 23.

The "Performance of Rotavirus and Oral Polio Vaccines in Developing Countries" (PROVIDE) study: description of methods of an interventional study designed to explore complex biologic problems.

Author information

1
Department of Medicine and Vaccine Testing Center, The University of Vermont College of Medicine, Burlington, Vermont; Departments of Medicine, The University of Virginia, Charlottesville, Virginia; The icddr,b, Dhaka, Bangladesh beth.kirkpatrick@med.uvm.edu.
2
Department of Medicine and Vaccine Testing Center, The University of Vermont College of Medicine, Burlington, Vermont; Departments of Medicine, The University of Virginia, Charlottesville, Virginia; The icddr,b, Dhaka, Bangladesh.

Abstract

Oral vaccines appear less effective in children in the developing world. Proposed biologic reasons include concurrent enteric infections, malnutrition, breast milk interference, and environmental enteropathy (EE). Rigorous study design and careful data management are essential to begin to understand this complex problem while assuring research subject safety. Herein, we describe the methodology and lessons learned in the PROVIDE study (Dhaka, Bangladesh). A randomized clinical trial platform evaluated the efficacy of delayed-dose oral rotavirus vaccine as well as the benefit of an injectable polio vaccine replacing one dose of oral polio vaccine. This rigorous infrastructure supported the additional examination of hypotheses of vaccine underperformance. Primary and secondary efficacy and immunogenicity measures for rotavirus and polio vaccines were measured, as well as the impact of EE and additional exploratory variables. Methods for the enrollment and 2-year follow-up of a 700 child birth cohort are described, including core laboratory, safety, regulatory, and data management practices. Intense efforts to standardize clinical, laboratory, and data management procedures in a developing world setting provide clinical trials rigor to all outcomes. Although this study infrastructure requires extensive time and effort, it allows optimized safety and confidence in the validity of data gathered in complex, developing country settings.

PMID:
25711607
PMCID:
PMC4385767
DOI:
10.4269/ajtmh.14-0518
[Indexed for MEDLINE]
Free PMC Article

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