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. 2018 Apr;32(2):139-152.
doi: 10.1007/s40259-018-0273-6.

Benefit Versus Risk Assessment of Rotavirus Vaccination in France: A Simulation and Modeling Analysis

Edouard Ledent  1 , Hugo Arlegui  2 , Hubert Buyse  3 , Peter Basile  3 , Naveen Karkada  4 , Nicolas Praet  5 , Gaëlle Nachbaur  6
Affiliations

Benefit Versus Risk Assessment of Rotavirus Vaccination in France: A Simulation and Modeling Analysis

Edouard Ledent et al. BioDrugs. 2018 Apr.

Abstract

Introduction: Two vaccines against rotavirus gastroenteritis (RVGE) in young children, Rotarix and RotaTeq, have been available in Europe since 2006. Vaccination against rotaviruses significantly reduces the burden of RVGE, but it is also associated with a very small increased risk of intussusception. In a benefit-risk analysis, the prevented RVGE burden is weighed against the possible excess of intussusception.

Purpose: The aim was to compare the estimated benefits and risks of Rotarix vaccination in France.

Methods: We estimated the benefits (vaccine-preventable RVGE hospitalizations and deaths) and risks (vaccine-caused intussusception hospitalizations and deaths) following two doses of Rotarix in a birth cohort of 791,183 followed for 3-5 years in France. We used data from peer-reviewed clinical and epidemiological studies or publications, and government statistics.

Results: Within the total number of French children below 5 years of age, we estimate vaccination could prevent a median 11,132 [95% credible interval (CI) 7842-14,408] RVGE hospitalizations and 7.43 (95% CI 3.27-14.68) RVGE deaths. At the same time, vaccination could cause an average of 6.86 (95% CI 2.25-38.37) intussusception hospitalizations and 0.0099 (95% CI 0.0024-0.060) intussusception deaths in the entire French birth cohort of infants below 1 year of age. Therefore, for every intussusception hospitalization and every intussusception death caused by vaccination, 1624 (95% CI 240-5243) RVGE hospitalizations and 743 (95% CI 93-3723) RVGE deaths are prevented, respectively, by vaccination.

Conclusions: The vaccine-prevented RVGE hospitalizations and deaths (benefit) greatly outweigh the excess potentially vaccination-related cases of intussusception (risk), indicating a favorable benefit-risk balance for Rotarix in France.

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Conflict of interest statement

Conflict of interest

Edouard Ledent, Hugo Arlegui, Hubert Buyse, Naveen Karkada, Gaëlle Nachbaur and Nicolas Praet are employed by the GSK group of companies. Hubert Buyse, Edouard Ledent, Gaëlle Nachbaur and Nicolas Praet also hold shares in the GSK group of companies. Peter Basile was an employee of the GSK group of companies at the time of the study and also held shares in the GSK group of companies. Hugo Arlegui is also a doctoral fellow whose research is financed by the Association Nationale pour la Recherche et la Technologie (ANRT) (Paris, France) and the GSK group of companies.

Funding

GlaxoSmithKline Biologicals SA was the funding source and was involved in all stages of study conduct and analysis. GlaxoSmithKline Biologicals SA also funded all costs associated with the development and the publishing of the present manuscript.

Trademarks

Rotarix is a trademark of the GSK group of companies. RotaTeq is a trademark of Merck & Co., Inc.

Figures

Fig. 1
Fig. 1
“Focus on the Patient” section: summary contextualizing the results and potential clinical research relevance and impact for the benefit of health care professionals
Fig. 2
Fig. 2
Two-dimensional plots of the overall reduction in the number of RVGE hospitalizations (a, b) and deaths (c, d) over 3 (a, c) and 5 years (b, d) risk windows (x axis) and the increase in numbers of IS hospitalizations (a, b) and deaths (c, d) post vaccination over two 7-day risk windows (y axis) for cohorts of 105 (hospitalization) and 106 (death) vaccinated French children. Each point represents the joint calculations of benefits and risks under a specific scenario selected at random from each of the random distributions of the input parameters. The results presenting the highest frequencies across the 106 simulations are colored in red. The plots illustrate the dominance of the hospitalization and death benefits in comparison to the hospitalization and death risks under all scenarios. D1 dose 1, D2 dose 2, hosp. hospitalization, IS intussusception, RVGE rotavirus gastroenteritis, sub. subjects
Fig. 2
Fig. 2
Two-dimensional plots of the overall reduction in the number of RVGE hospitalizations (a, b) and deaths (c, d) over 3 (a, c) and 5 years (b, d) risk windows (x axis) and the increase in numbers of IS hospitalizations (a, b) and deaths (c, d) post vaccination over two 7-day risk windows (y axis) for cohorts of 105 (hospitalization) and 106 (death) vaccinated French children. Each point represents the joint calculations of benefits and risks under a specific scenario selected at random from each of the random distributions of the input parameters. The results presenting the highest frequencies across the 106 simulations are colored in red. The plots illustrate the dominance of the hospitalization and death benefits in comparison to the hospitalization and death risks under all scenarios. D1 dose 1, D2 dose 2, hosp. hospitalization, IS intussusception, RVGE rotavirus gastroenteritis, sub. subjects
Fig. 3
Fig. 3
Sensitivity analysis assessing the impact of the variability of model parameters on the BR ratio for hospitalization (a) and death (b) in children 0–3 years of age. The tornado diagrams show on the x axis the variations of the BR ratio around its mean value because of variations of the main input parameters. The vertical line on the left part of the diagrams represents a BR ratio equal to 1. The left and right limits of each horizontal bar indicate the change in BR ratio calculated for the 1 and 99% percentile values of the input parameter mentioned. Other symbols indicate the BR variations expected for those percentiles of the input parameter. BR benefit–risk, D1 dose 1, D2 dose 2, IS intussusception, Max Maximum, Min Minimum, Q1 first quartile, Q3 third quartile, RR relative risk, RVGE rotavirus gastroenteritis, VE vaccine efficacy
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