'What' and 'How' to Measure in Allergy and Clinical Immunology: A Systematic Review of Core Outcome Sets and Outcome Harmonisation Processes

BACKGROUND: Heterogeneity in outcome reporting and inconsistent use of outcome measurement instruments in allergy and clinical immunology research affects the comparability, synthesis, and clinical applicability of study findings. Harmonisation efforts, particularly Core Outcome Set (COS) development, aim to address these challenges by establishing standardised, evidence-based and consensus-driven outcome recommendations. This systematic review aims to map available COS and other harmonisation processes (HP) in allergy and clinical immunology, evaluate their methodological approaches, and assess their alignment with established development standards.

METHODS: We systematically searched MEDLINE, EMBASE, and the COMET Initiative database until June 7, 2024 to identify COS and HP. We included studies if they provided recommendations on 'core' outcomes and/or outcome measurement instruments. Data extraction included disease focus, methodological approach, stakeholder involvement, and adherence to the Core Outcome Set-STAndards for Development criteria. We synthesised the data at the initiative (process) level rather than the publication level because harmonisation initiatives are frequently iterative and reported across multiple papers (e.g., protocol, Delphi rounds, consensus statement, and subsequent instrument-selection outputs).

RESULTS: A total of 15,612 records were identified, with 44 studies (representing 22 initiatives both finished and in development) meeting inclusion criteria. The majority of initiatives focused on asthma (n = 9), followed by eczema (atopic dermatitis n = 2; hand eczema = 1; eczema = 1), urticaria (n = 2), allergic rhinitis (n = 2), chronic rhinosinusitis (n = 1), celiac disease (n = 1), Immunoglobulin E (IgE)-mediated food allergy (n = 1), eosinophilic esophagitis (n = 1), and hereditary angioedema (n = 1). No COS or HP addressed drug allergy, anaphylaxis, or other immune-mediated allergic conditions. 'Quality of life' was consistently included in all COS with 'signs and symptoms', 'exacerbations' and 'disease control' frequently selected as well. Methodological approaches to COS development varied widely, with most employing Delphi surveys, consensus meetings, and stakeholder involvement, though levels of engagement differed. COS developers inconsistently adhered to Core Outcome Set-STAndards for Development criteria, with some initiatives demonstrating rigorous methodology while others lacked transparency in key developmental steps.

CONCLUSION: This review highlights growing efforts to harmonise outcome assessment in allergy and clinical immunology. Major gaps remain in coverage and methodological rigour. Quality of life and patient-reported symptoms are frequently recommended outcomes, yet definitions and measurement tools are inconsistent. Strengthening methodological consistency and expanding COS development to neglected areas are critical next steps to improve outcome reliability and comparability in the field.