Study type

Study topic, other

Vaccine effectiveness

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
Ecological
Other

Non-interventional study design, other

Test-negative design
Study drug and medical condition

Name of medicine

ABRYSVO

Name of medicine, other

Respiratory syncytial virus vaccine (bivalent, recombinant)

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

The TND study will include all infants through 9 months of age who were born at 32 weeks of gestational age or greater and born 14 days or more after start of the first seasonal ABRYSVO vaccination campaign, born to an individual who were expected to reach the indicated ABRYSVO vaccination window during a local ABRYSVO vaccination season, admitted to one of the participating hospital sites with symptoms of respiratory infection, met the definition of LRTD, and had a respiratory specimen collected within 10 days prior to hospital admission through 3 days after a hospital admission with an RSV test result through standard of care testing.

To complement the VE estimates generated in the TND study, we will use the cases from the primary objective of the TND study as a cohort of participants to describe the endpoints in the descriptive cohort study.

The ecologic before-and-after study will include information for all children <= 24 months of age meeting eligibility criteria in post-ABRYSVO program implementation years (2024, 2025, and 2026 in Argentina; 2025 and 2026 in Uruguay) and in five historical RSV seasons pre-ABRYSVO program implementation (2016 through 2019, as well as the 2023 season for Argentina; 2017 through 2019, as well as 2023 and 2024 seasons for Uruguay.

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

Pregnant women

Special population of interest, other

Pregnant individuals who have received ABRYSVO vaccination

Estimated number of subjects

2000
Study design details

Study design

Three design approaches will be used in this study:
(i) retrospective test negative design (TND)
(ii) retrospective descriptive cohort design
(iii) retrospective ecologic before-and-after design

Main study objective

The primary objective of the TND study is to estimate ABRYSVO VE against RSV-associated LRTD hospitalization among infants from birth through 6 months of age.

Secondary and exploratory objectives of the TND study include (but are not limited to) estimating ABRYSVO VE against the primary outcome according to timing of vaccination and timing of vaccine co-administration (simultaneous or sequential), estimating ABRYSVO VE against the primary outcome according to subtype (RSV-A/RSV-B), estimating ABRYSVO VE against RSV-associated severe LRTD hospitalization among infants from birth through 6 months of age, and evaluating duration of protection and interval-specific vaccine effectiveness against RSV-associated LRTD hospitalization.

The exploratory objectives of the descriptive cohort study are to describe the infant characteristics, timing, and severity/clinical features of infants who develop severe hospitalized LRTD or who die in hospital, and to describe use of healthcare resources during the index RSV hospitalization.

The exploratory objectives of the ecologic study are to estimate the impact of ABRYSVO introduction by evaluating the number and rate of RSV-associated and all-cause respiratory outcomes (i.e., LRTD hospitalization, LRTD critical care hospitalization, LRTD in-hospital death) before and after ABRYSVO introduction both descriptively and using quasi-experimental approaches.

Setting

This hospital-based retrospective study will be conducted within a research network of comprised of independent hospital sites across Argentina and Uruguay, coordinated by the iTRIALS study team. Each participating hospital site conducts standard of care respiratory viral testing during the RSV season, using polymerase chain reaction (PCR) and/or indirect immunofluorescence (IIF) techniques. For critical respiratory illness (e.g., requiring admission to neonatal intensive care unit [NICU]/pediatric intensive care unit [PICU]; illness resulting in death), PCR testing is used by all sites to determine viral etiology. The study will use data collected during routine standard of care clinical encounters available in medical records, the national surveillance systems (SNVS 2.0 in Argentina and the Sistema Integrado de Vigilancia in Uruguay) and supplemented with information from the official national vaccine registry (NOMIVAC in Argentina and Sistema Informatico de Vacunas in Uruguay) for maternal ABRYSVO vaccination status.

Outcomes

The primary outcome of the TND study is RSV-associated LRTD hospitalization among infants occurring <=180 days after birth.

Other outcomes of the TND study include (but are not limited to) RSV-associated severe LRTD hospitalization among infants occurring <=180 days after birth, RSV-associated LRTD hospitalization among infants occurring <=180 days after birth by gestational age at ABRYSVO vaccination, by time from ABRYSVO vaccination to birth, by simultaneous or sequential administration with none or >=1 other vaccine, by subtype (RSV-A/RSV-B), by ABRYSVO vaccination status in a previous pregnancy, by breastfeeding status, by infant high-risk status, and by RSV-associated in-hospital death.

The outcomes that will be evaluated in the descriptive cohort study of infants <=270 days of age hospitalized with RSV-associated LRTD include severe LRTD hospitalization, in-hospital death, and use of healthcare resources.

The outcomes of the ecologic study include RSV-associated and all-cause respiratory outcomes (i.e., LRTD hospitalization, LRTD critical care hospitalization, LRTD in-hospital death).

Data analysis plan

For the TND study, a logistic regression model will be used to compute an odds ratio (OR), comparing the odds of maternal ABRYSVO vaccination during pregnancy between test-positive cases and test-negative controls. From the OR, the VE will be calculated as (1 - OR) x 100%. A multivariable logistic regression model will be used to compute an adjusted OR (aOR) from which we will derive final VE estimates, adjusted for potential confounding, according to the formula: VE = (1 - aOR) x 100%. In secondary and exploratory objectives, VE estimates for the primary outcome will be stratified by several characteristics.

For the descriptive cohort study, infant characteristics, timing, severity/clinical features, and use of healthcare resources during the index hospitalization will be described overall and stratified according to maternal ABRYSVO status. Among infants born to individuals who received ABRYSVO vaccine during pregnancy (i.e., breakthrough cases), we will describe the gestational age at ABRYSVO vaccination and the time interval from vaccination to birth.

For the ecologic before-and-after study, the impact of maternal ABRYSVO introduction on rates of study outcomes among infants <=6 months over multiple RSV seasons will be described over time and by infant age group and hospital site. All analyses will be conducted using data from Argentina and Uruguay separately, beginning in the 2024 RSV season in Argentina and in the 2025 RSV season in Uruguay and continuing in future RSV seasons with comparison to several pre-ABRYSVO implementation seasons.

Quasi-experimental approaches (controlled interrupted time series analyses and difference-in-differences analyses) will be conducted to further quantify the impact. We will also evaluate study outcomes in older pediatric age groups as well as include several negative control outcomes to contextualize the findings in the post-ABRYSVO time period.