{
  "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).",
  "authors": [
    {
      "affiliations": [
        "Department of Population Medicine, Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA",
        "Harvard Medical School, Boston, Massachusetts, USA"
      ],
      "name": "Sruthi Adimadhyam"
    },
    {
      "affiliations": [
        "GSK, Wavre, Belgium"
      ],
      "name": "Dominique Luyts"
    },
    {
      "affiliations": [
        "GSK, Rockville, Maryland, USA"
      ],
      "name": "Driss Oraichi"
    },
    {
      "affiliations": [
        "GSK, Wavre, Belgium"
      ],
      "name": "Quentin Deraedt"
    },
    {
      "affiliations": [
        "GSK, Wavre, Belgium"
      ],
      "name": "Jean-Yves Pircon"
    },
    {
      "affiliations": [
        "Department of Biostatistics, Epidemiology, and Informatics, Center for Clinical Epidemiology and Biostatistics, Center for Real-World Effectiveness and Safety of Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA"
      ],
      "name": "Warren B Bilker"
    },
    {
      "affiliations": [
        "Department of Population Medicine, Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA"
      ],
      "name": "Anna A Agan"
    },
    {
      "affiliations": [
        "Department of Population Medicine, Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA"
      ],
      "name": "Rajani Rajbhandari"
    },
    {
      "affiliations": [
        "Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Health Care Policy, and Aging Research, Rutgers University, New Brunswick, New Jersey, USA"
      ],
      "name": "Dean M Carbonari"
    },
    {
      "affiliations": [
        "CVS Health, Blue Bell, Pennsylvania, USA"
      ],
      "name": "Djeneba Audrey Djibo"
    },
    {
      "affiliations": [
        "CVS Health, Blue Bell, Pennsylvania, USA"
      ],
      "name": "Xi Wang"
    },
    {
      "affiliations": [
        "HealthPartners Institute, Minneapolis, Minnesota, USA"
      ],
      "name": "Margaret B Nolan"
    },
    {
      "affiliations": [
        "Humana Healthcare Research, Inc, Louisville, Kentucky, USA"
      ],
      "name": "Andrea DeVries"
    },
    {
      "affiliations": [
        "Humana Healthcare Research, Inc, Louisville, Kentucky, USA"
      ],
      "name": "Mano Selvan"
    },
    {
      "affiliations": [
        "Humana Healthcare Research, Inc, Louisville, Kentucky, USA"
      ],
      "name": "Qianli Ma"
    },
    {
      "affiliations": [
        "Carelon Research, Wilmington, Delaware, USA"
      ],
      "name": "Anna E Wentz"
    },
    {
      "affiliations": [
        "Carelon Research, Wilmington, Delaware, USA"
      ],
      "name": "Kimberly Daniels"
    },
    {
      "affiliations": [
        "Department of Population Medicine, Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA",
        "Harvard Medical School, Boston, Massachusetts, USA"
      ],
      "name": "Richard Platt"
    },
    {
      "affiliations": [
        "Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Health Care Policy, and Aging Research, Rutgers University, New Brunswick, New Jersey, USA",
        "Division of Infectious Diseases, Department of Medicine, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey, USA"
      ],
      "name": "Vincent Lo Re III"
    },
    {
      "affiliations": [
        "Department of Population Medicine, Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA",
        "Harvard Medical School, Boston, Massachusetts, USA"
      ],
      "name": "Noelle M Cocoros"
    }
  ],
  "title": "Postmarketing safety surveillance for GSK’s AS01E-adjuvanted respiratory syncytial virus prefusion F protein-based vaccine in the USA: protocol for a non-interventional postauthorisation safety study",
  "uid": "46739a9b-abe2-5c09-97ae-f6b64ef0b62a"
}