Introduction: The Haem-A-QoL is frequently utilized in haemophilia clinical trials and captures relevant aspects of disease impact. Thresholds for some domains 'Physical Health' (PH), 'Sports & Leisure' (S&L) and 'Total Score' (TS) have previously been identified to benchmark the amount of change that is meaningful to patients, but not been independently confirmed.
Aim: The objective of this analysis was to determine the clinically important responder (CIR) thresholds for these three domains.
Methods: CIR thresholds in adult persons with haemophilia A (PwHA) enrolled in HAVEN 1, 3 and 4 studies were determined for improvements from baseline to 24 weeks of emicizumab prophylaxis using anchor-based methodology with the EQ-5D-5L as the validated anchor, cumulative distribution functions (CDF) and distribution-based methodology. The results were compared with previously published thresholds.
Results: At baseline and after 24 weeks of emicizumab prophylaxis, Haem-A-QoL data from 241/258 patients were available. Concordance was observed between the Haem-A-QoL and EQ-5D-5L in patterns of improvement, deterioration or lack of change. CDF estimates of the Haem-A-QoL PH and TS grouped by response categories on the Mobility, Pain/Discomfort and Usual Activities EQ-5D-5L domains demonstrated the same pattern of responses to each scale; distribution-based estimates were 11.9 for PH, 13.9 for S&L, and 8.3 for TS.
Conclusion: Our responder thresholds are mostly consistent with those proposed by Wyrwich et al (cut-offs of -10 and -7 for PH and TS, respectively). The majority of responders to emicizumab prophylaxis had improvements greater than the previously reported 10-point reduction in PH and 7-point reduction in TS.
Keywords: Haem-A-QoL; emicizumab; haemophilia A; health-related quality of life; meaningful change; responder threshold.
© 2020 The Authors. Haemophilia published by John Wiley & Sons Ltd.