{
  "abstract": "Background Immunotherapies exhibit class- and target-specific safety challenges, particularly diagnosis and attribution of immune-mediated adverse reactions (imARs), also referred to as immune-related adverse events (irAEs). Recent, global consensus-building efforts have resulted in new clinical coding standards and several publications outlining diagnostic and management recommendations for patients experiencing irAEs in diverse organ systems. These standardization efforts have not yet fully propagated into safety event recordings during clinical trials. Current case report forms (CRF) specific to irAE/imARs vary widely in how these events are captured, including differences in attribution, grading, terminology, and follow-up practices. This inconsistency limits data quality, impedes regulatory alignment, and reduces the interpretability of safety profiles.Methods A Delphi-style consensus process was used to engage 23 experts in immunotherapy, oncology trial design, data standards, and regulatory review. An initial landscape review of five oncology CRF templates identified heterogeneity in terminology, severity grading, automated triggers, treatment linkage, and event monitoring beyond 90 days. Thirteen experts participated in structured surveys and discussion sessions to evaluate proposed CRF elements across domains such as attribution, timing, and immune-specific sub-forms.Results Consensus was achieved on the use of Medical Dictionary for Regulatory Activities (MedDRA) terms for event coding and Common Terminology Criteria for Adverse Events (CTCAE) for severity grading, with additional modules recommended for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Agreed-upon CRF elements included:Protocol-specific checkboxes and body system-based entryPredefined irAE/imAR term lists and immune-active treatment linkageAutomated logic to trigger sub-forms for syndromic eventsUnique adverse event identifiers to reduce duplication and enable longitudinal trackingStructured attribution fields allowing investigator and sponsor input with justificationLogs for immunosuppressive therapy and hospitalization eventsNarrative fields for serious adverse eventsNeed for long term follow up, potentially well beyond 90 daysGrade change forms and ‘no new event’ checkboxes to support long-term follow-upThe framework defines a tiered structure with required core fields and optional specialized modules, balancing data completeness with operational feasibility and alignment to CDISC and MedDRA standards.Conclusions This consensus provides a structured framework for improving irAE/imAR documentation in immunotherapy trials. Implementation of standardized CRFs with automated logic and attribution controls may enhance regulatory review, support pooled analyses, and enable cross trial comparisons and integration with real-world datasets. Pilot testing across trial networks is recommended to assess feasibility and refine implementation strategies.",
  "authors": [
    {
      "affiliations": [
        "Project Data Sphere, Morrisville, NC, USA"
      ],
      "name": "Jon McDunn"
    },
    {
      "affiliations": [
        "Project Data Sphere, Morrisville, NC, USA"
      ],
      "name": "Ravikumar Komandur"
    },
    {
      "affiliations": [
        "Project Data Sphere, Morrisville, NC, USA"
      ],
      "name": "Eleanor McCabe"
    },
    {
      "affiliations": [
        "Clinical Data Interchange Standards Consortium (CDISC), Austin, TX, USA"
      ],
      "name": "Rebecca Baker"
    },
    {
      "affiliations": [
        "F. Hoffmann-La Roche Ltd, Basel, Switzerland"
      ],
      "name": "Bogdana I Balas"
    },
    {
      "affiliations": [
        "MRCT Center, Boston, MA, USA"
      ],
      "name": "Samjhana Bogati"
    },
    {
      "affiliations": [
        "Gilead, Foster City, CA, USA"
      ],
      "name": "John William Bond"
    },
    {
      "affiliations": [
        "MSD Innovation and Development GmbH, Zurich, Zurich, Switzerland"
      ],
      "name": "Nathalie de Bois Brillant"
    },
    {
      "affiliations": [
        "Brown University Health, Providence, RI, USA"
      ],
      "name": "Matthew J Hadfield"
    },
    {
      "affiliations": [
        "University of Texas Southwestern Medical Center, Dallas, TX, USA"
      ],
      "name": "Mitchell S von Itzstein"
    },
    {
      "affiliations": [
        "Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Boston, MA, USA"
      ],
      "name": "David Kozono"
    },
    {
      "affiliations": [
        "Harvard Medical School, Boston, MA, USA",
        "Massachusetts General Hospital, Boston, MA, USA"
      ],
      "name": "Caleb RS McEntire"
    },
    {
      "affiliations": [
        "Roche Products Ltd, Whitwell, UK"
      ],
      "name": "Amanda Messer"
    },
    {
      "affiliations": [
        "University of New Mexico, Albuquerque, NM, USA"
      ],
      "name": "David J Savage"
    },
    {
      "affiliations": [
        "Harvard Medical School, Boston, MA, USA",
        "Dana-Farber Cancer Institute, Bethesda, MD, USA"
      ],
      "name": "Elad Sharon"
    },
    {
      "affiliations": [
        "Gary G. Walker, LLC, CDISC Standards Consulting, Napoleon, MO, USA"
      ],
      "name": "Gary G Walker"
    },
    {
      "affiliations": [
        "Project Data Sphere, Morrisville, NC, USA"
      ],
      "name": "Sean Khozin"
    }
  ],
  "title": "1053 Shaping the future of immunotherapy safety through consensus—standardization of case report forms",
  "uid": "a53bf14f-b723-5bd2-9fe1-fe9e326e8ca3"
}