Jennifer Quinn1, Kathleen A Delaney2, Wing Yen Wong2, Wolfgang Miesbach3, Monika Bullinger4. 1. BioMarin Pharmaceuticals UK Ltd, London, UK. 2. BioMarin Pharmaceutical Inc., Novato, CA, USA. 3. Medical Clinic 2, Institute of Transfusion Medicine, University Hospital Frankfurt, Frankfurt, Germany. 4. Department of Medical Psychology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
Abstract
Purpose: 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 <0.01). Internal consistency analysis showed good reliability for all domains (Cronbach's alpha >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.
Purpose: 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 <0.01). Internal consistency analysis showed good reliability for all domains (Cronbach's alpha >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.
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