title: 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.
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.
authors.affiliation: 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.
authors.forename: Beth D
authors.initials: BD
authors.lastname: Kirkpatrick
authors.affiliation: 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.
authors.forename: E Ross
authors.initials: ER
authors.lastname: Colgate
authors.affiliation: 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.
authors.forename: Josyf C
authors.initials: JC
authors.lastname: Mychaleckyj
authors.affiliation: 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.
authors.forename: Rashidul
authors.initials: R
authors.lastname: Haque
authors.affiliation: 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.
authors.forename: Dorothy M
authors.initials: DM
authors.lastname: Dickson
authors.affiliation: 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.
authors.forename: Marya P
authors.initials: MP
authors.lastname: Carmolli
authors.affiliation: 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.
authors.forename: Uma
authors.initials: U
authors.lastname: Nayak
authors.affiliation: 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.
authors.forename: Mami
authors.initials: M
authors.lastname: Taniuchi
authors.affiliation: 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.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Naylor
authors.affiliation: 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.
authors.forename: Firdausi
authors.initials: F
authors.lastname: Qadri
authors.affiliation: 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.
authors.forename: Jennie Z
authors.initials: JZ
authors.lastname: Ma
authors.affiliation: 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.
authors.forename: Masud
authors.initials: M
authors.lastname: Alam
authors.affiliation: 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.
authors.forename: Mary Claire
authors.initials: MC
authors.lastname: Walsh
authors.affiliation: 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.
authors.forename: Sean A
authors.initials: SA
authors.lastname: Diehl
authors.affiliation: 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.
authors.forename: William A
authors.initials: WA
authors.lastname: Petri
mesh_terms: D000284:Administration, Oral; D000914:Antibodies, Viral / Q000097:blood; D001459:Bangladesh; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003906:Developing Countries; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D011051:Poliomyelitis / Q000276:immunology / Q000517:prevention & control*; D017955:Poliovirus / Q000276:immunology*; D011055:Poliovirus Vaccine, Oral / Q000008:administration & dosage / Q000276:immunology; D023321:Poliovirus Vaccines / Q000008:administration & dosage* / Q000276:immunology; D012401:Rotavirus / Q000276:immunology*; D012400:Rotavirus Infections / Q000276:immunology / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000008:administration & dosage* / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D011055:Poliovirus Vaccine, Oral; D023321:Poliovirus Vaccines; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated