Presentation (CTI)

OBJECTIVES: In rare diseases, empirical evidence is routinely limited due to small patient populations and absence of randomized controlled trials. The Delphi method, a structured iterative expert consensus technique, is increasingly used to address evidence gaps in health technology assessment (HTA), economic modelling, and guideline development. This targeted literature review (TLR) aimed to map applications, opportunities, and pitfalls of Delphi consensus as a surrogate for missing evidence in rare diseases.
METHODS: A TLR was conducted using a structured PubMed search based on predefined eligibility criteria. Eligible studies employed Delphi or modified Delphi approaches to address clinical, epidemiological, or economic evidence gaps in rare disease populations. Data were extracted on disease area, evidence gap type, panel composition, rounds, consensus threshold, and limitations across 256 records. Thematic synthesis identified cross-cutting patterns.
RESULTS: Of 256 records, 131 (51%) employed Delphi or modified Delphi methods; the remainder used expert panels or consensus conferences. Disease areas included neurology and neuromuscular disorders (n=39), metabolic disorders (n=31), pulmonology (n=31), and immunology or rheumatology (n=24); 196 records (77%) focused on rare disease populations. Modified Delphi was the most common design (n=42); 40 panels were international and 31 online. Predominant use cases were diagnostic criteria or pathways (n=111), treatment recommendations (n=81), HRQoL or utility values (n=44), and HTA or economic parameters (n=14). Pre-specified thresholds were reported in 29 Delphi studies. Recurring pitfalls included inadequate transparency or reporting (n=24), general methodological limitations (n=20), absent validation (n=14), limited panel representativeness (n=10), and undefined consensus thresholds (n=6).
CONCLUSIONS: Delphi methods are widely applied in rare diseases for diagnostic and treatment guidance and offer a viable route to HTA where trial-level data are absent. Critical pitfalls are poor transparency, absent validation, panel homogeneity, and inconsistent consensus definitions. Standardized reporting and pre-specified thresholds are essential to strengthen credibility of consensus-derived evidence in rare disease decision-making.