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

Systematic review and meta-analysis
Study drug and medical condition

Name of medicine

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

Studies to be included will be those which evaluate immunogenicity and efficacy/effectiveness of RSVpreF vaccination of pregnant persons in pregnant and postpartum persons and their infants.
Eligible studies will include randomized and post-licensure observational studies reporting efficacy or effectiveness outcomes with sample sizes of at least 50 participants, and immunogenicity outcomes with at least 10 participants.

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)

Special population of interest

Nursing women
Pregnant women
Study design details

Study design

The study design is a LSR and meta-analysis to evaluate the effectiveness and immunogencity of RSVpreF maternal vaccine in infants and the effectiveness of the RSVpreF maternal vaccine in pregnant and postpartum individuals.

Main study objective

1. To evaluate the efficacy/effectiveness of maternal RSVpreF vaccination during pregnancy in preventing infants from RSV-specific and all-cause respiratory illness.
2. To evaluate the immune response associated with RSVpreF vaccination and how long it lasts in individuals vaccinated during pregnancy in the real-world.
3. To evaluate the efficacy/effectiveness of maternal RSVpreF vaccination during pregnancy in preventing maternal RSV-specific and all-cause respiratory illness.

Setting

Studies to be included will be those which evaluate immunogenicity and efficacy/effectiveness of RSVpreF vaccination of pregnant persons in pregnant and postpartum persons and their infants.
Selected studies will include post-marketing observational and randomized studies reporting efficacy or effectiveness outcomes with sample sizes of at least 50 participants, and immunogenicity outcomes with at least 10 participants.

Outcomes

Outcomes included in the LSR will depend on the outcomes in published studies included. The following outcomes may be evaluated if data are sufficient, as well as other not specified outcomes.
Effectiveness outcomes: RSV detection, RSV acute respiratory illness [ARI, lower respiratory tract illness (LRTI) or disease (LRTD)] , RSV hospitalization, RSV LRTI/LRTD hospitalization, RSV complications including secondary bacterial infection, respiratory failure, multiorgan failure, death [including case fatality rate (CFR)], All-cause LRTI/LRTD, All-cause LRTI/LRTD hospitalization (does not require confirmation of etiology), Asymptomatic RSV infection , Antibiotic use in infants with RSV infection.
Immunogenicity outcomes: Humoral immune responses (quantity and durability) including RSV-A and RSV-B antibody titers and cellular immune responses, RSV viral load.

Data analysis plan

The final data set of pooled data is then summarized and mapped using PowerBI to create an interactive dashboard for data visualization, programmed by the IECS team and based on this protocol.
Meta-analyses will be performed using RShiny (RStudio language), incorporating random-effects models and proportional meta-analyses to synthesize the data based on algorithms that select and automatically calculate the meta-analyses estimates.
Provided that data are available and methodologically suitable, aggregate meta-analyses will be performed for each comparison in accordance with the Cochrane Handbook of Systematic Reviews of Interventions, employing random-effects meta-analysis for primary analyses.
Proportional meta-analyses will be performed to summarize frequencies from 1-sample studies. R statistical software will be used to analyze the data. Hazard ratios, risk ratios, or odds ratios and corresponding 95% confidence intervals (CI) will be computed for dichotomous outcomes, whereas mean differences or standardized mean differences will be determined for continuous outcomes.
Proportions with 95% CI will be determined for non-comparative studies. For reporting efficacy/effectiveness outcomes, measures will be converted into vaccine efficacy whenever feasible. Adjusted effect measures will be prioritized (e.g., by age, region, etc) over unadjusted estimates. Heterogeneity will be explored through subgroup analyses. Publication bias will be formally assessed by funnel plots and Egger and Begs tests. Sensitivity analysis will be undertaken by excluding high-risk bias studies.