A Description of the Statistical Methods for the Vaccine Impact on Diarrhea in Africa (VIDA) Study.

Background: Diarrheal diseases remain a health threat to children in low- and middle-income countries. The Vaccine Impact on Diarrhea in Africa (VIDA) study was a 36-month, prospective, matched case-control study designed to estimate the etiology, incidence, and adverse clinical consequences of moderate-to-severe diarrhea (MSD) in children aged 0-59 months. VIDA was conducted following rotavirus vaccine introduction at 3 censused sites in sub-Saharan Africa that participated in the Global Enteric Multicenter Study (GEMS) ∼10 years earlier. We describe the study design and statistical methods of VIDA and where they differ from GEMS.
Methods: We aimed to enroll 8-9 MSD cases every 2 weeks from sentinel health centers in 3 age strata (0-11, 12-23, 24-59 months) and 1 to 3 controls matched by age, sex, date of case enrollment, and village. Clinical, epidemiological, and anthropometric data were collected at enrollment and ∼60 days later. A stool specimen collected at enrollment was analyzed by both conventional methods and quantitative PCR for enteric pathogens. For the matched case-control study, we estimated the population-based, pathogen-specific attributable fraction (AF) and attributable incidence adjusted for age, site, and other pathogens, and identified episodes attributable to a specific pathogen for additional analyses. A prospective cohort study nested within the original matched case-control study allowed assessment of (1) the association between potential risk factors and outcomes other than MSD status and (2) the impact of MSD on linear growth.
Conclusions: GEMS and VIDA together comprise the largest and most comprehensive assessment of MSD conducted to date in sub-Saharan Africa populations at highest risk for morbidity and mortality from diarrhea. The statistical methods used in VIDA have endeavored to maximize the use of available data to produce more robust estimates of the pathogen-specific disease burden that might be prevented by effective interventions.
Competing Interests: Potential conflicts of interest. K. L. K. reports financial support from PATH for travel to a Shigella vaccine meeting, and grants to her institution from Institut Pasteur and the National Institute of Allergy and Infections Diseases for vaccine research. M. A. W. reports receiving funding from the Centers for Disease Control and Prevention (CDC) and the Institute of Tropical Medicine. Y. L. reports receiving the following grants or contracts paid to their institution: R01NS122855 (National Institutes of Health), U54CK000615-01 (Centers for Disease Control and Prevention), 1R18 HS027750-01 (Agency for Healthcare Research and Quality), R03 AG067927 (National Institutes of Health), U01 AI143493 (National Institutes of Health), U01 AI148054 (National Institutes of Health), U01 AI148081 (National Institutes of Health), NCT04078022 (Institut Pasteur), HHS-NIH-NIAID-BAA2018 (National Institutes of Health), R01 HD093946-01 (National Institutes of Health), 2R01-DA026868-06A1 (National Institutes of Health), 2R01-AA014988-12A1 (National Institutes of Health), R01 AA014988-S1 (National Institutes of Health), R01 DK109323 (National Institutes of Health), R01-NR016269 (National Institutes of Health), Geneva Foundation (National Institute for Allergy and Infectious Diseases [NIAID] prime), R01-HD075936 (National Institutes of Health), and BAA FY2018-OADS-01 (Centers for Disease Control and Prevention). They also report serving as the data safety monitoring board statistician for the clinical trial entitled “Matching Perfusion and Metabolic Activity in HFpEF (MPMA),” and reviewed data from National Institute on Drug Abuse/National Institute on Alcohol Abuse and Alcoholism studies involving human subjects All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
(© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)