Acute multi-organ dysfunction (aMOD): Brighton Collaboration case definition and guidelines for data collection, analysis, and presentation of immunization safety data

This is a new Brighton Collaboration case definition of acute multi-organ dysfunction (aMOD) as an adverse event following immunization (AEFI). It is intended for use in clinical trials and post-licensure pharmacovigilance activities to facilitate safety data comparability across multiple settings. It is not intended to guide clinical management, but it can serve as an outcome measure of disease severity in the context of vaccine efficacy and effectiveness studies. The case definition was developed by a group of subject matter and Brighton Collaboration process experts as part of the Coalition for Epidemic Preparedness Innovations (CEPI)-funded Safety Platform for Evaluation of vACcines (SPEAC). The Brighton Collaboration case definition includes a scoping review of the literature and expert consensus used to define levels of diagnostic certainty (LOC) for aMOD and provides specific guidelines for related data collection and analysis. The document underwent peer review by a Reference Group of vaccine safety stakeholders and aMOD experts to ensure case definition useability, applicability, and scientific integrity. aMOD is defined as acute dysfunction involving two or more of six organ systems: respiratory, cardiovascular, renal, neurologic, hepatic, and hemostatic. A key feature is the requirement that organ dysfunction occur within the same clinical episode, with onset within 7 days, allowing sequential or simultaneous involvement. Five LOC are included for each of the six organs. The overall aMOD case definition also comprises five LOC categories: Level 1 (Definite), Level 2 (Probable), Level 3 (Possible), Level 4 (Insufficient information), and Level 5 (Not a case). The criteria build on established organ dysfunction frameworks while adapting them for global application. Importantly, AEFI case definitions are separate from causality assessment. This case definition provides a standardized approach to aMOD case ascertainment, bridging concepts of organ dysfunction with Brighton Collaboration requirements for reproducible vaccine safety assessment. It also provides a standard case definition that can be used by stakeholders to harmonize assessment of AEFI to enable rigorous analysis and comparison of AEFI surveillance across settings and studies.