Abstract
INTRODUCTION: In May 2023, the US Food and Drug Administration (FDA) initially approved an AS01(E)-adjuvanted respiratory syncytial virus (RSV) prefusion F protein-based vaccine (adjuvanted RSVPreF3) for adults aged ≥60 years. The approval was expanded in June 2024 to include adults 50-59 years of age at increased risk for RSV-associated lower respiratory tract disease. In this paper, we describe the protocol of a postmarketing safety study evaluating the association between adjuvanted RSVPreF3 and new-onset Guillain-Barré syndrome (GBS), acute disseminated encephalomyelitis (ADEM) and atrial fibrillation (AF) among adults ≥50 years of age in the USA and provide our rationale for key methodological decisions. METHODS AND ANALYSIS: The potential associations between adjuvanted RSVPreF3 and GBS, ADEM and AF will be evaluated using secondary healthcare data and the self-controlled risk interval (SCRI) design. Data from five research partners in the USA spanning August 2023 through June 2030 will be used for the conduct of yearly monitoring queries and, sample size permitting, SCRI analyses. Claims-based definitions for new-onset outcomes (first diagnosis in 365 days) are: ≥1 inpatient diagnosis for GBS and ADEM; ≥1 inpatient or ≥2 ambulatory/emergency diagnoses for AF. The primary risk and control windows are 1-42 and 43-84 days, respectively, for GBS and ADEM; and 1-8 and 9-16 days for AF. SCRI analyses for GBS and ADEM will include chart-confirmed cases. SCRI analyses for AF will adjust for the positive predictive value obtained from validation against charts. Conditional Poisson regression will be used to calculate incidence rate ratios. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Boards (IRB) of Harvard Pilgrim Health Care Institute; WIRB-Copernicus Group, Inc and its affiliates (collectively, 'WCG'); WCG IRB, Inc; and Sterling IRB, with Federal Wide Assurance (FWA) numbers FWA00000100, FWA00033319 and FWA00025632, respectively, for all participating research partners. Study results will be shared with the US FDA and publicly disseminated through national or international clinical or scientific conferences and peer-reviewed publications. REGISTRATION: This protocol has been registered in the Heads of Medicines Agencies-European Medicines Agency Real World Data Catalogues (EUPAS1000000486).