A post-authorisation safety study of ABRYSVO in immunocompromised, or renally or hepatically impaired adults aged 60 years and older in a real world setting in Europe and UK

Study type

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

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine:
  ABRYSVO
• Anatomical Therapeutic Chemical (ATC) code:
  (J07BX05) respiratory syncytial virus vaccines

  respiratory syncytial virus vaccines

Population studied

• Short description of the study population:
  The target population will consist of individuals who are immunocompromised, or renally or hepatically impaired (evaluated as separate populations and if appropriate, as a combined population) who are at least 60 years of age on the date of vaccination (i.e, index date for the vaccinated cohort) or on the matched index date (for the unvaccinated cohort), and who have at least 12 months of medical history in one of the data sources with no record of RSV vaccination in that 12 month period and who have at least one day of post-index follow up. Immunocompromised or renally impaired or hepatically impaired status will be ascertained via coded diagnoses, treatments, procedures, and/or laboratory values, as appropriate, at index date or in the 12-month baseline period prior to the index date.
• Age groups:
  Adults (18 to < 65 years)

  Elderly (≥ 65 years)
• Special population of interest:
  Hepatic impaired

  Immunocompromised

  Renal impaired
• Estimated number of subjects:
  2356

Study design details

• Study design:
  A retrospective comparative cohort design will serve as the primary study design. In addition to the primary study design (i.e, comparative cohort design), for an appropriate subset of the study outcomes, the self-controlled risk interval (SCRI) design will also be used.
• Main study objective:
  To estimate the incidence rates and rate ratios of safety events of interest in immunocompromised, or renally or hepatically impaired adults aged 60 years and older who receive ABRYSVO compared to a relevant comparator group who does not receive ABRYSVO (evaluated as separate populations and if appropriate, as a combined population).
• Setting:
  The study will be conducted in a source population of the participating population-based electronic healthcare data sources from the VAC4EU network.
• Comparators:
  To be included in the unvaccinated cohort, individuals must meet the following criteria: ; - No vaccine record on index date: They must not have a record of receiving any vaccine, including the RSV vaccines, on the index date.; - No RSV vaccination in baseline period: They must not have a record of receiving any RSV vaccine during the 12-month baseline before the index date.; ; For the SCRI design, person-time in the risk interval will be considered “exposed,” while person-time in the control interval will be considered “unexposed.”
• Outcomes:
  Acute disseminated encephalomyelitis; diabetes mellitus type I; Guillain-Barré syndrome; narcolepsy; thrombocytopenia (idiopathic); thrombosisthrombocytopenia syndrome; acute cardiovascular injury; arrhythmia; coronary artery disease; heart failure; microangiopathy; myocarditis and pericarditis; stress cardiomyopathy; coagulation disorders: disseminated intravascular coagulation, venous thromboembolism (pulmonary embolism, deep vein thrombosis), thrombotic microangiopathy, cerebral venous thrombosis, thrombotic thrombocytopenia syndrome, ischemic stroke, myocardial infarction, haemorrhage; single organ cutaneous vasculitis; thrombocytopenia with venous thromboembolism; Bell’s palsy; generalised convulsion; meningoencephalitis; transverse myelitis; acute respiratory distress syndrome; erythema multiforme; anaphylaxis; death (any causes)
• Data analysis plan:
  Detailed methodology for summary and statistical analyses of data collected in this study will be documented in a statistical analysis plan (SAP), which will be dated, filed, and maintained by the sponsor and PI. The SAP may modify the plans outlined in the protocol; any major modifications of primary endpoint definitions or their analyses will be reflected in a protocol amendment. The SAP will also provide additional detail regarding the evaluation of a threshold of excess risk for each of the outcomes of interest. This will be determined based on background incidences for each event, in addition to prespecified significance level (e.g., alpha = 0.01 or 0.05) and power. All analyses will be conducted using R version R-4.0.3 or higher.; ; The SAP will contain additional detail of the data analysis and meta-analysis. One interim analysis and report may be conducted. The interim report will be limited to descriptive analyses. Comparative analyses will be included in the final report. Further details will be described in the SAP.; ; All analyses will be conducted separately for the 3 populations of interest: immunocompromised, renally impaired, or hepatically impaired; and if appropriate, in the combined population. Prior to any combined analysis, a Higgin’s I2 statistic will be used to assess the heterogeneity in the primary outcomes across the 3 populations of interest. If the percentage of heterogeneity estimated by I2 is high (e.g., >50%; specific threshold to be specified in the SAP), a combined effect may be estimated using adapted methods such as a random-effects model.