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

Jennifer Quinn; Kathleen A Delaney; Wing Yen Wong; Wolfgang Miesbach; Monika Bullinger

doi:10.2147/PROM.S357555

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

Patient Relat Outcome Meas. 2022 Jul 18:13:169-180. doi: 10.2147/PROM.S357555. eCollection 2022.

Authors

Jennifer Quinn¹, Kathleen A Delaney², Wing Yen Wong², Wolfgang Miesbach³, Monika Bullinger⁴

Affiliations

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.

Keywords: Haemo-QOL-A; clinically important difference; gene therapy; psychometric testing; quality of life; severe hemophilia A.

Associated data

ClinicalTrials.gov/NCT03370913
ClinicalTrials.gov/NCT02576795

Grants and funding

Funding for this research was provided by BioMarin Pharmaceutical Inc.