Integrating Clinical, Functional, and Patient-Reported Outcomes in Haemophilia Care: A Delphi-Based Consensus on a...

Background: An appropriate and effective management of haemophilia is currently based on a multidimensional evaluation of treatment adequacy. Current clinical practice however is still lacking standardised tools able to combine clinical, functional, and patient-reported outcomes. In this study a structured Monitoring Tool for haemophilia A and B was developed and validated through a Delphi-based expert consensus process. This study represents an expert consensus-based validation of a monitoring framework, rather than a clinical validation in patient cohorts. The tool is intended for use by haemophilia treaters during routine follow-up visits to support structured treatment reassessment. Score categories reflect the need for clinical re-evaluation or potential treatment optimisation, rather than disease severity. Methods: Italian haemophilia specialists were asked to participate to a panel over a two-round Delphi process. Experts rated the relevance of several predefined clinical domains-pharmacokinetics, bleeding episodes, joint health, adherence and quality of life (QoL)-and the individual items within each domain for patients on prophylactic or on-demand treatment. Consensus was defined by responses within an interquartile range (IQR) < 8. Section and item weights and Likert-based scoring values were used to reach a composite score between 0 and 100. Results: Consensus was achieved for all domains and items across haemophilia types and treatments, prophylaxis and on demand (Haemophilia A: 16 and 12 participants; Haemophilia B: 12 and 9, respectively). With reference to prophylaxis domains, bleeding episodes received the highest domain weight (31-32%), followed by joint health (27-29%) and adherence/QoL (21-23%) and pharmacokinetics (18-19%). For on-demand treatment, pharmacokinetics was excluded; bleeding episodes (38-40%) and joint health (35-37%) remained dominant. At the item level, dynamic joint health indicators (HJHS and HEAD-US changes) and longitudinal QoL changes consistently received the highest weights. The final scoring system categorised results as Excellent (0-25), Suboptimal (26-50), Poor (51-75), or Critical (76-100). Conclusions: The Delphi-validated Monitoring Tools provide a structured, weighted, and clinically relevant framework for assessing treatment adequacy in haemophilia A and B across prophylactic and on-demand settings. These tools allow multidimensional outcome assessment and may support a more consistent, personalised therapeutic decision-making. A prospective validation of the tool in clinical cohorts is warranted.