Altering rotavirus vaccine schedules may improve vaccine performance in low- and middle-income countries. We analyzed data from clinical trials of the monovalent (RV1) and pentavalent (RV5) rotavirus vaccines in low- and middle-income countries to understand the association between vaccine dose timing and severe rotavirus gastroenteritis incidence.
We assessed the association between variations in rotavirus vaccine administration schedules and severe rotavirus gastroenteritis risk. We used the complement of the Kaplan–Meier survival estimator to estimate risk differences for different schedules. To adjust risk differences (RDs) for confounding, we calibrated estimates in the vaccinated arm using estimates from the placebo arm.
There were 3,114 and 7,341 children included from the RV1 and RV5 trials, respectively. The 18-month adjusted severe rotavirus gastroenteritis risk was 4.0% (95% confidence interval [CI] = 1.1, 7.1) higher for those receiving their first RV5 dose at <6 versus ≥6 weeks. For RV1, there was a 4.0% (95% CI = 0.0, 8.2) increase in 12-month adjusted risk for a 4- versus 6-week interval between doses. Further analysis revealed those receiving their first RV5 dose at 3–4 and 5–7 weeks had 2.9% (95% CI = 0.8, 5.3) and 1.3% (95% CI = −0.3, 3.0), respectively, higher risk compared with those at 9–12 weeks. Those receiving their first dose at 8 weeks had the lowest risk (RD: −2.6% [95% CI = −5.4, −0.1]) compared with those at 9–12 weeks.
A modest delay in rotavirus vaccination start and increase in interval between doses may be associated with lower severe rotavirus gastroenteritis risk in low- and middle-income countries.
aDepartment of Epidemiology, University of North Carolina (UNC)-Chapel Hill, Chapel Hill, NC
bDepartment of Family Medicine, UNC-Chapel Hill, Chapel Hill, NC
cDepartment of Biostatistics, UNC-Chapel Hill, Chapel Hill, NC
dMEASURE Evaluation, Carolina Population Center, UNC-Chapel Hill, NC.
Submitted March 4, 2018; accepted July 27, 2018.
Applications to access the GSK and Merck and Co, Inc. clinical trial data can be submitted to ClinicalStudyDatarequest.com and http://engagezone.msd.com/ds_documentation.php, respectively. Computing code can be made available by the first author.
Supported by the University of North Carolina Graduate School Dissertation Completion Fellowship. S.B.-D. was supported by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (NIH) [grant number 1R56A1108515-01]. M.J.F. receives investigator-initiated research funding and support as Principal Investigator from the National Heart, Lung, and Blood Institute at the NIH [R01 HL118255] and as a Co-Investigator from the NIH National Institute on Aging [R01 AG023178]; from the NIH National Center for Advancing Translational Sciences [1UL1TR001111]; and from AstraZeneca. M.J.F. receives salary support from the Center for Pharmacoepidemiology in the Department of Epidemiology, Gillings School of Global Public Health (current members: GlaxoSmithKline, UCB BioSciences, Merck). M.A.B. was supported by a grant from the National Institutes of Health [1R21HD080214-01A1].
Disclosure: Data for this article were provided by GlaxoSmithKline (GSK), Rixensart, Belgium, through a third party, ClinicalStudyDatarequest.com, and Merck and Co, Inc., Kenilworth, NJ. Neither company had involvement in this study design and analysis. Both Merck and Co, Inc., Kenilworth, NJ, and GSK, Rixensart, Belgium, were given the opportunity to comment on this article before publication. All decisions regarding the content of this article were made by the authors. J.F.G. was employed by Merck and Co, Inc., Kenilworth, NJ, as a graduate research assistant from January to December 2014 to work on research related to their rotavirus vaccine. M.J.F. is a member of the Scientific Steering Committee (SSC) for a postapproval safety study of an unrelated drug class funded by GSK. All compensation for services provided on the SSC is invoiced by and paid to University of North Carolina Chapel Hill. M.J.F. receives salary support from the Center for Pharmacoepidemiology in the Department of Epidemiology, Gillings School of Global Public Health (current members: GSK, UCB BioSciences, and Merck and Co, Inc.). M.J.F. does not accept personal compensation of any kind from any pharmaceutical company. M.A.B. has received investigator-initiated research funding from the National Institutes of Health and through contracts with the Agency for Healthcare Research and Quality (AHRQ)’s DEcIDE program and the Patient-Centered Outcomes Research Institute (PCORI). Within the past 3 years, he has received research support from Amgen and AstraZeneca and has served as a scientific advisor for Amgen, Merck and Co, Inc., GSK, UCB BioSciences, and RxAnte. Within the past 3 years, M.A.B. has received research support from Amgen and AstraZeneca and has served as a scientific advisor for Amgen, Merck, GSK, Genentech, TargetPharma, and RxAnte. M.A.B. owns equity in NoviSci, LLC, a data sciences company. The other authors have no conflicts to report.
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Correspondence: Joann F. Gruber, Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, McGavaran-Greenburg Hall, Campus Box 7435, Chapel Hill, NC 27599. E-mail: email@example.com.