Development and validation of a US quality of life instrument for hereditary angioedema due to C1 inhibitor deficiency

Ann Allergy Asthma Immunol. 2024 Dec;133(6):703-711.e6. doi: 10.1016/j.anai.2024.07.018. Epub 2024 Jul 20.

Abstract

Background: Hereditary angioedema (HAE) attacks are unpredictable, cause a substantial and enduring burden of illness, and are potentially fatal. Because of issues unique to the US health care system, there is a need for a US-validated, HAE-specific quality of life (QoL) instrument.

Objective: To develop and validate a US HAE-specific QoL instrument according to US Food and Drug Administration guidelines and established methodologies.

Methods: We generated 41 QoL-related items likely relevant to US patients with HAE due to C1 inhibitor (C1INH) deficiency (HAE-C1INH) and performed a 10-patient pilot study to refine the question wording. A total of 415 US patients with HAE-C1INH completed the initial 41-item instrument online, thereby providing data for item reduction, factor analysis, and the assessment of validity and reliability. We used a multiple linear regression to identify the drivers of the total and domain scores. Convergent validity analysis was used to assess the extent to which the HAE-C1INH QoL instrument (HAE-C1INH-QoL) is theoretically related to the angioedema-QoL instrument (AE-QoL).

Results: Item reduction and factor analysis yielded a final instrument of 31 items across 5 domains, and the assessment analysis showed that the HAE-C1INH-QoL is valid and reliable. Attack frequency and severity were statistically significant factors that influenced the total and domain scores. Correlation analysis of the 2 instruments indicated that 8 items of the HAE-C1INH-QoL were not included or well-described in the AE-QoL.

Conclusion: The HAE-C1INH-QoL is the first HAE-specific QoL tool validated in the United States. When compared with the AE-QoL, the items in our instrument are more relevant to US patients with HAE.

Publication types

  • Validation Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Angioedemas, Hereditary* / psychology
  • Complement C1 Inhibitor Protein*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects
  • Quality of Life*
  • Reproducibility of Results
  • Surveys and Questionnaires
  • United States
  • Young Adult

Substances

  • Complement C1 Inhibitor Protein