Evaluating the benefits of RSV maternal vaccination using a Scottish National Dataset. (BORLAND)

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Effectiveness study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  ABRYSVO
• Anatomical Therapeutic Chemical (ATC) code:
  (J07BX05) respiratory syncytial virus vaccines

  respiratory syncytial virus vaccines
• Medical condition to be studied:
  Respiratory syncytial virus infection

Population studied

• Short description of the study population:
  This will be a whole population birth cohort study of all live-born infants born in Scotland during the study period. In Scotland, all infants are assigned a unique identifier, the Community Health Index (CHI) at birth. CHI is a common identifier across all National Health Service (NHS) healthcare encounters and allows linkage of all healthcare data to statutory datasets such as death records. ; The patient population will include all live-born infants born in Scotland over an 18-month accrual period, from 01 September 2024 – 28 February 2026 (or end of RSV season) and their mothers (approximately 69,000 mother-infant pairs). ; Selection criteria for the population were based on the time period of the RSV season in Scotland and the earliest gestational age eligible for ABRYSVO vaccination, per the MHRA. ; All infants will be followed for 12 months after birth; thus, the last outcome assessment will be approximately 28 February 2027.
• Age groups:
  • Neonate

    • Preterm newborn infants (0 – 27 days)
    • Term newborn infants (0 – 27 days)
  • Infants and toddlers (28 days – 23 months)

Study design details

• Study design:
  This study is a retrospective cohort design that will be conducted within routinely collected national healthcare and statutory demographic datasets held by PHS and National Records of Scotland (NRS).
• Main study objective:
  To estimate the vaccine effectiveness (VE) of ABRYSVO vaccination during pregnancy against polymerase chain reaction (PCR)-confirmed RSV-associated lower respiratory tract disease (LRTD) hospitalisation among infants from birth through 6 months of age.
• Setting:
  This will be a whole population birth cohort study of all live-born infants born in Scotland during the study period. In Scotland, all infants are assigned a unique identifier, the Community Health Index (CHI) at birth. ; CHI is a common identifier across all National Health Service (NHS) healthcare encounters and allows linkage of all healthcare data to statutory datasets such as death records. ; The patient population will include all live-born infants born in Scotland over an 18-month accrual period, from 01 September 2024 – 28 February 2026 (or end of RSV season) and their mothers (approximately 69,000 mother-infant pairs). ; Selection criteria for the population were based on the time period of the RSV season in Scotland and the earliest gestational age eligible for ABRYSVO vaccination, per the MHRA. All infants will be followed for 12 months after birth; thus, the last outcome assessment will be approximately 28 February 2027.;
• Outcomes:
  All RSV-specific infant outcomes will be based on a positive PCR test and will be assessed year-round, during both the RSV season and off-season. PHS surveillance data will be used to determine RSV seasonal periods.; RSV-specific outcomes will include: ; • PCR-confirmed RSV-associated LRTD hospitalisation; • PCR-confirmed RSV-associated hospitalisation ; Identification of RSV-specific outcomes will be based on the first positive PCR test from Electronic Communication of Surveillance Scotland (ECOSS), occurring during the relevant follow-up period. ;
• Data analysis plan:
  • Descriptive population and vaccination analysis: Baseline characteristics of mothers and infants, as well as vaccination timing and intervals, will be summarized using frequencies for categorical variables and summary statistics for continuous variables, stratified by ABRYSVO vaccination status. ; • RSV-specific infant outcome analysis: Incidence rates for RSV-associated outcomes will be calculated overall and by vaccination status, with follow-up from birth through 6 and 12 months. Adjusted hazard ratios from inverse probability of treatment weights (IPTW) weighted Cox regression models will be used to estimate vaccine effectiveness (VE), accounting for confounders.; • All-cause infant outcome analysis: Hospitalisations for all-cause acute respiratory infections and lower respiratory tract disease will be analyzed similarly through 12 months, using first-episode and total-episode approaches with weighted IPTW Poisson regression to estimate adjusted incidence rate ratios and VE. ; • Exploratory subgroup and hospitalisation characteristics: Characteristics of RSV hospitalisations and potential predictors of breakthrough RSV hospitalisation among vaccinated infants will be examined using descriptive statistics and regression models, with attention to sample size limitations and privacy rules for small counts.;