Psychometric Validation of the Haemo-QOL-A in Participants with Hemophilia A Treated with Gene Therapy

Abstract

Jennifer Quinn,1 Kathleen A Delaney,2 Wing Yen Wong,2 Wolfgang Miesbach,3 Monika Bullinger4 1BioMarin Pharmaceuticals UK Ltd, London, UK; 2BioMarin Pharmaceutical Inc., Novato, CA, USA; 3Medical Clinic 2, Institute of Transfusion Medicine, University Hospital Frankfurt, Frankfurt, Germany; 4Department of Medical Psychology, University Medical Center Hamburg Eppendorf, Hamburg, GermanyCorrespondence: Jennifer Quinn, BioMarin Pharmaceuticals UK Ltd, 10 Bloomsbury Way, London, WC1A 2SL, UK, Tel [phone], Email [email protected]: The hemophilia-specific health-related quality of life (HRQOL) questionnaire (Haemo-QOL-A) is validated for detecting QOL changes following standard therapy for hemophilia A, but has not been rigorously evaluated after gene therapy. This post hoc analysis evaluated the psychometric properties of Haemo-QOL-A in adult people with severe hemophilia A (PWSHA) receiving valoctocogene roxaparvovec (AAV5-hFVIII-SQ) in 2 clinical trials (phase 1/2, NCT02576795; phase 3, NCT03370913).Patients and Methods: Adult PWSHA (factor VIII levels ≤ 1 IU/dL) received 1 AAV5-hFVIII-SQ infusion (6× 1013 vg/kg). Participants were assessed using the Haemo-QOL-A and the EuroQOL (EQ)-5D-5L and visual analog scale (VAS) questionnaires pre- and post-infusion. Psychometric analyses included convergent and discriminant validity, internal consistency, and reliability. Clinically important difference (CID) was estimated using 3-point change in EQ-5D-5L VAS as anchor.Results: Haemo-QOL-A data were analyzed from 7 (phase 1/2, 3-year follow-up) and 16 participants (phase 3, 26-week analysis). Change in Haemo-QOL-A Total Scores correlated with EQ-5D-5L VAS score change at 26 weeks (Pearson’s correlation 0.77). At 26 weeks, increased Haemo-QOL-A Physical Functioning was associated with decreased EQ-5D-5L Pain and Discomfort and decreased Anxiety and Depression (Spearman’s Rank correlations − 0.73 and − 0.62, respectively, P 0.7) except Treatment Concern (Cronbach’s alpha = 0.31). Anchor-based CID estimates were met for Haemo-QOL-A Total Score (≥ 5.5) and domain scores (≥ 6) for Consequences of Bleeding, Physical Functioning, Role Functioning, and Worry.Conclusion: Our preliminary results suggest that the Haemo‐QOL‐A is a valid, reliable instrument for HRQOL assessment in PWSHA undergoing gene therapy. Future research should be undertaken to confirm these findings in a larger number of participants.Keywords: severe hemophilia A, gene therapy, quality of life, Haemo-QOL-A, psychometric testing, clinically important difference

Keywords

• severe hemophilia a
• gene therapy
• quality of life
• haemo-qol-a
• psychometric testing
• clinically important difference