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

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.

Conflict of interest statement

Jennifer Quinn was an employee and stockholder of BioMarin Pharmaceutical Inc., London, UK at the time of the study. Wing Yen Wong and Kathleen A Delaney are employees of BioMarin Pharmaceutical Inc., Novato, CA, USA. Wolfgang Miesbach has received speaker honoraria and project grants from Bayer, BioMarin Pharmaceutical Inc., Biotest, CSL Behring, Chugai, Freeline, LFB, Novo Nordisk, Octapharma, Pfizer, Roche, Sanofi, Sobi, Takeda/Shire, and uniQure. Monika Bullinger has received speaker honoraria and project grants from Bayer, BioMarin Pharmaceutical Inc., Janssen Cilag, Otsuka Lundbeck, and Pfizer. The authors report no other conflicts of interest in this work.

© 2022 Quinn et al.

Figures

Figure 1
Figure 1
Linear regression plot of change in Haemo-QOL-A Total Score vs change in EQ-5D-5L VAS scores, from baseline to week 26, modified intent-to-treat population, phase 3 study.
Figure 2
Figure 2
Difference between mean Haemo-QOL-A Total and domain scores in EQ-5D-5L VAS participant subgroups (UK population norm [n = 9]), modified intent-to-treat population, phase 3 study. an = 23 for VAS score <population norm. *P <0.05. **P <0.01.

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