A Post-Marketing Near Real-Time Safety Surveillance of Respiratory Syncytial Virus Vaccine for Guillain-Barre Syndrome (GBS) among Older Adults in the United States

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
• Medical condition to be studied:
  Guillain-Barre syndrome

Population studied

• Short description of the study population:
  The study population will include Centers for Medicare & Medicaid Services (CMS) Medicare Fee-for-Service (FFS) beneficiaries aged 65 years of age or older and individuals aged 60-64 years IQVIA PharMetrics Plus database who receive one dose of Abrysvo vaccine administration during the surveillance period and meet all other eligibility criteria.; ; The self-controlled risk interval (SCRI) analysis will be conducted in the Medicare populations identified in both the 2023/2024 and 2024/2025 RSV seasons; the RCA analysis will be launched in the 2024/2025 RSV season, with cumulative data from the 2023/2024 RSV season.
• Age groups:
  Adults (46 to < 65 years)

  Elderly (≥ 65 years)
• Estimated number of subjects:
  2000000

Study design details

• Study design:
  This is a non-interventional cohort study among adults ≥ 65 years enrolled in CMS Medicare database and adults 60-64 years enrolled in IQVIA PharMetrics Plus database. The surveillance period will span 2 RSV seasons (2023/2024 and 2024/2025 seasons), beginning on Abrysvo’s approval 31 May 2023.
• Main study objective:
  • To conduct near real-time monitoring of the incidence of GBS following vaccination with Abrysvo among individuals aged 65 years of age or older enrolled in CMS Medicare databases among individuals aged 60-64 years of age or older enrolled in IQVIA PharMetrics Plus database; and; ; • To assess if there is an elevated risk of GBS following vaccination with Abrysvo among individuals aged 65 years of age or older enrolled in CMS Medicare databases and individuals aged 60-64 years of age or older enrolled in IQVIA PharMetrics Plus database, using RCA and SCRI complementary study designs; and; ; • To descriptively monitor the incidence of GBS following vaccination with ABRYSVO in individuals aged 60-64 years enrolled in PharMetrics Plus database.;
• Setting:
  The source population is U.S. Medicare beneficiaries available in the CMS Medicare FFS administrative database and individuals aged 60-64 enrolled in the IQVIA PharMetrics Plus database. This database includes Medicare Parts A, B, and D data, covering inpatient and outpatient encounters and drug/vaccine prescriptions.; ; Individuals aged 60 years of age or older who receive Abrysvo vaccine (ie, exposure) who meet the eligibility criteria described in protocol Sections 9.2.1.1 and 9.2.1.2 will be included in the study. The Abrysvo vaccine record will be identified using CPT (Current Procedural Terminology), HCPCS (Healthcare Common Procedure Coding System), and NDC (National Drug Code) codes. The details of the exposure and other inclusion and exclusion criteria are defined in protocol Section 9.3.;
• Outcomes:
  The outcome of interest is GBS diagnosis, which will be identified from inpatient (IP) and outpatient (OP) claims using ICD-10-CM code G 61.0. ; ; An incident GBS case will be defined as the first occurrence of a primary discharge diagnosis of GBS in the IP setting post-vaccination. The date of the case’s onset will be defined as the date of hospitalization unless there is a claim with a GBS diagnosis in another medical setting (e.g., OP) in the prior 7 days. In that case, the earlier claim, irrespective of healthcare setting, will represent the date of onset. This claims-based algorithm in Medicare data has a PPV of 71.2% – 78.6% when validated against medical records using the Brighton criteria and has been used to reliably identify GBS cases among Medicare beneficiaries.; ; The risk window of 42 days post-vaccination is generally recommended by the Brighton Collaboration GBS case definition. Within the Abrysvo clinical and surveillance studies, over 90% of GBS events have been found to occur within 21 days of vaccination. In this study, for the RCA, the primary risk interval is defined as 1 - 21 days post-vaccination to prioritize timely analysis; a secondary risk interval of 1 - 42 days post-vaccination will be analyzed as part of a sensitivity analysis. For the SCRI, the primary post-vaccination risk interval is defined as 1 – 21 days post-vaccination and the secondary post-vaccination risk interval is defined as 1 – 42 days post-vaccination. The control interval for the SCRI analysis is defined as 43 – 84 days post-vaccination. For the SCRI analysis, GBS diagnosis will be identified during the risk or the control intervals (1-84 days) to compare the risk of GBS; occurrence within the two intervals.
• Data analysis plan:
  Covariates will be assessed among the study population aimed for SCRI analysis and RCA analysis (protocol Section 9.1.3). Patient demographic and clinical characteristics including age on index, gender, race, geographic region, concurrent immunizations, prior infections, and selected comorbidities will be reported. Demographic variables will be assessed on the index date or during the baseline period, as described in protocol Section 9.3.3. If multiple records exist, the record closest to the index date will be used.; ; Continuous variables will be summarized using mean ± SD, median, and interquartile range. Categorical variables will be summarized using counts and proportions. 95% CIs will be provided where applicable. ; ; 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. The SAP may modify the plans outlined in the protocol; any major modifications of outcome definitions or their analyses would be reflected in a protocol amendment.