Study type

Study topic

Human medicinal product

Study type

Non-interventional study

Scope of the study

Disease epidemiology
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

Medical condition to be studied

Guillain-Barre syndrome
Population studied

Short description of the study population

The source population for the GBS epidemiology component of the study will be individuals age ≥18 years with incident GBS from up to 3 national health plans.

The source population for the signal detection component of the study will include non-pregnant individuals 18-59 years of age at increased risk of RSV-LRTD and administered ABRYSVO or a comparator vaccine.

The source population for the signal evaluation component will include non-pregnant individuals 18-59 years of age who received ABRYSVO vaccination.

Age groups

  • Adult and elderly population (≥18 years)
    • Adults (18 to < 65 years)
Study design details

Study design

This is a PASS using a cohort study design to monitor the incidence of GBS in ABRYVSO-vaccinated adults 18-59 years of age at increased risk of RSV-LRTD. Additionally, analyses of the epidemiology and natural history of GBS in the US will also be conducted.

Main study objective

Signal Detection: Among non-pregnant individuals 18-59 years at increased risk of RSV-LRTD, compare observed GBS case counts after ABRYSVO vaccination against expected GBS case counts via rapid cycle analysis (RCA).

Signal Evaluation: Among non-pregnant individuals 18-59 years of age, assess risk of GBS in the 21 days
or 42 days (depending on length of risk window) following ABRYSVO vaccination using a self-controlled risk interval design.

Setting

Individuals must meet all of the following inclusion criteria to be eligible for inclusion in the GBS epidemiology and incidence analysis:
Research eligible at the participating research partner (RP);
≥18 years of age during the study period, January 2017 – December 2024;
Have ≥365 days of medical and pharmacy coverage preceding cohort entry, with gaps of ≤45 days permitted (they are considered administrative gaps, not lapses in health plan coverage); and
Meet the algorithm for incident GBS (outlined in protocol Table 1).

Individuals must meet all of the following inclusion criteria to be eligible for inclusion in the medical record review and exploratory data mining analyses:
Research eligible at the participating RP;
≥18 years of age during the study period, January 2017 – December 2024;
Have ≥365 days of medical and pharmacy coverage preceding cohort entry, with gaps of ≤45 days permitted; and
Meet the algorithm for incident GBS (outlined in protocol Table 1).

Comparators

GBS, defined as a diagnosis (G61.0) in the primary position in the inpatient setting or, incident GBS in any setting and any position, with a hospitalization within 7 days, again with GBS as the primary diagnosis.

If the signal evaluation phase commences due to a statistically significant positive association between risk of GBS and ABRYSVO vaccination from one of the rapid cycle analyses in the signal detect phase, then medical record confirmation of GBS cases in the SCRI study will be conducted as part of the signal evaluation.

Outcomes

Outcome for rapid cycle analysis (RCA) – Incident GBS will be identified using the same algorithm as Research Question 1, which is based on Goud and colleagues work: a GBS diagnosis (G61.0) in the primary position in the inpatient setting or, incident GBS in any setting and any position, with a hospitalization within 7 days, again with GBS as the primary diagnosis.
Incidence will be defined using a 365-day washout for G61.0 or G65.0 in any care setting. GBS cases will not be confirmed via medical record review for any RCA, although a statistically significant positive association between risk of GBS and ABRYSVO vaccination from an RCA would trigger medical record review for the subsequent SCRI study.

Outcome for SCRI design study – If the SCRI study commences due to a statistically significant positive association between risk of GBS and ABRYSVO vaccination from one of the RCAs, medical record confirmation of GBS cases in the SCRI study will be conducted as part of the signal evaluation. The medical record associated with the inpatient encounter where GBS was diagnosed will be requested.
The record for the first subsequent ambulatory encounter with a neurologist, if applicable, will also be requested. If the SCRI study commences after 4 seasons of the RCA in the absence of a statistically significant finding of increased risk, GBS cases will not be confirmed via medical record review, but rather results will be adjusted based on the PPVs from Research Question 1.

Data analysis plan

To evaluate the epidemiology of GBS, annual incidence rates and corresponding 95% CIs for GBS will be estimated overall and for subgroups (e.g., age, sex, comorbidities, and region), showing how and to what degree incidence rates vary across groups and over the study period.
Descriptive statistics of adults who meet the GBS algorithm will be reported regarding their demographics, clinical characteristics, risk factors, treatment, and outcomes.

In the signal detection phase of the study, observed ABRYSVO-exposed GBS cases will be compared against expected GBS counts using sequential hypothesis testing.

In the signal evaluation phase of the study, case-centered logistic regression will be used to estimate incidence rate ratios with 95% CIs and attributable risk with 95% CIs per 100,000 doses and 100,000 person-years.