Study type

Study topic

Disease /health condition
Human medicinal product

Study type

Non-interventional study

Scope of the study

Drug utilisation
Safety study (incl. comparative)

Data collection methods

Secondary use of data
Non-interventional study

Non-interventional study design

Cohort
Study drug and medical condition

Anatomical Therapeutic Chemical (ATC) code

(J07BK) Varicella zoster vaccines
Varicella zoster vaccines
(J07BD54) measles, combinations with mumps, rubella and varicella, live attenuated
measles, combinations with mumps, rubella and varicella, live attenuated

Medical condition to be studied

Encephalitis
Population studied

Short description of the study population

The study population will include all individuals aged between 9 months and 18 years who are present in the data source during the study period from 1st January 2017 until the latest date of data availability, with at least 365 days of data availability (reduced to 90 days for children ≤1 years) before index date. For Objective 4, we will require children and adolescents to receive at least one dose of varicella vaccines (V) or measles-mumps-rubella-varicella vaccines (MMRV) during the study period.
For the SCRI analysis, children and adolescents who are not eligible for vaccination, including children and adolescents with contraindications (acquired immunodeficiency syndrome (AIDS) or symptomatic HIV infection, immunosuppression due to leukaemia, lymphoma, generalised malignancy, severe combined immunodeficiency (SCID), immunosuppressive therapy, and transplantation) or a record of previous varicella infection will be excluded. Children and adolescents with a record of another live vaccine in the 28 days before or after study vaccine administration, which is the minimum allowable interval for live vaccines, will also be excluded.

Age groups

  • Paediatric Population (< 18 years)
    • Neonate
      • Preterm newborn infants (0 – 27 days)
      • Term newborn infants (0 – 27 days)
    • Infants and toddlers (28 days – 23 months)
    • Children (2 to < 12 years)
    • Adolescents (12 to < 18 years)
Study design details

Study design

Population-level descriptive analysis will be conducted to study the vaccine uptake, patient characterisations, and background rates for encephalitis. We will then conduct the self-controlled risk intervals analyses to assess the association between vaccination,varicella infection, and encephalitis.

Main study objective

1. To describe the vaccine uptake of V/MMRV by vaccine type, dose, brand, country, and to describe the characteristics of vaccine recipients.
2. To describe the background rates of encephalitis in the general paediatric population, and to estimate the crude incidence rates of encephalitis following varicella infection/chickenpox diagnosis.
3. To assess the association between V/MMRV vaccines and varicella infection (chickenpox) with encephalitis among children and adolescents aged 9 months to 18 years by age group and country

Setting

This study will be conducted using routinely collected data from one primary care data source linked to hospital data, and three national registries in the DARWIN EU® network of data partners from four European countries. All data were a priori mapped to the OMOP CDM.

Outcomes

For Objective 1, the analysis will describe:
• Vaccine uptake, defined as the absolute number of children and adolescents who received a
specified varicella vaccine dose(s) among eligible children.
• Vaccination coverage, defined as the proportion of children that received the specified number of
varicella vaccine doses in the relevant age group by age milestones (e.g., by the time of their 2nd
birthday) among the eligible children.
For objectives 2 to 4, the outcome of interest is encephalitis. Encephalitis will be identified using the
phenotype developed in a previous DARWIN EU® study (DARWIN EU® - Background incidence rates of
selected vaccine adverse events of special interest (AESIs)).
Two definitions of encephalitis will be included:
a.) “Any encephalitis”: this will use the “narrow” cohort from the AESI study
b.) “Unspecific encephalitis and encephalitis due to varicella or varicella containing vaccination will
be included”: this will start from the “narrow” cohort from the AESI study and exclude concepts
that have a specific cause listed that is not relevant for this study. Therefore. unspecific encephalitis
and encephalitis due to varicella or vaccination will be included. This phenotype will be developed
during the implementation stage.