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New Instrument for the Evaluation of Prodromes and Attacks of Hereditary Angioedema (HAE-EPA)

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Abstract

A disease-specific, patient-reported outcome instrument suitable for evaluation of prodromes and attacks of hereditary angioedema (HAE) is a clinical unmet need. We constructed such instrument and examined its validity, acceptability, and discriminative ability. Sixty-six patients participated in a survey addressing their demographics, social, and medical status. Discriminant content validity involved: (1) construct definition by in-depth cognitive debriefing interviews, (2) item selection identifying relevant categories, and (3) judgment of the format whereby questionnaires were tested on experienced patients and its content/reliability was validated. Prodromes and attacks affecting certain body systems (domains) were organized in “clusters”. Internal consistency, content, and convergent validities were analyzed. Analyses of variance and regression models were used to evaluate the discriminative ability of the instrument to differentiate between attacks and prodromes. The study demonstrates very high internal consistency (Cronbach’s α: attacks 0.88–0.98, prodromes 0.78–0.98). Analysis of variance confirmed significant differences between all dimensions and in pre-defined clusters (F (4, 61) = 45.74, p < 0.001, Eta2 = 0.77). Significant correlations were found between dimensions of prodromes and attacks. Prodromes are associated but differentiated from attacks. Correlations in severity were high for all domains. Interactions were found between prodromes and patients' experience in illness. In conclusion, the new Prodrome-Attack Evaluation questionnaire (HAE-EPA) is capable of distinguishing attacks and prodromes of HAE, as well as determining associations between the two interrelated phenomena. The new instrument achieves the required discriminative ability, acceptability, and content validity/reliability and therefore can be used as a reliable tool for the investigation of prodromes, attacks, and their relationships.

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Data Availability

Iris Leibovich Nassi RN, PhD thesis (Tel Aviv University).

Abbreviations

BK:

Bradykinin

C1-INH:

Complement 1-esterase Inhibitor

GI:

Gastrointestinal

HAE:

Hereditary angioedema

PRO:

Patient-reported outcome

HAE-EPA:

HAE Evaluation of Prodromes and Attacks

HRQoL:

Health-related quality of Life

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Funding

ILN received educational grants from the Stanley Steyer Foundation (Tel Aviv University, Israel) and CSL-Behring (Marburg, Germany).

Author information

Authors and Affiliations

  1. Angioedema Research Center, Barzilai University Medical Center, 2 Ha’histadrout St, 7830604, Ashkelon, Israel

    Iris Leibovich-Nassi & Avner Reshef

  2. Tel Aviv University, Tel Aviv, Israel

    Iris Leibovich-Nassi & Hava Golander

  3. Safra Pediatric Medical Center, Ramat Gan, Israel

    Raz Somech

  4. Bar Ilan University, Ramat Gan, Israel

    Dov Har-Even

Authors
  1. Iris Leibovich-Nassi
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  2. Hava Golander
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  3. Raz Somech
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  4. Dov Har-Even
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  5. Avner Reshef
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Contributions

Concept and design:ILN, HG, AR.

Acquisition of data:ILN.

Analysis and interpretation of data:ILN, DH-E, HG.

Drafting of the manuscript:ILN, AR.

Critical revision for intellectual content: ILN, AR, HG, RS, DH-E.

Statistical analysis:ILN, DH-E.

Supervision:AR, HG, RS.

Corresponding author

Correspondence to Avner Reshef.

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The authors declare that they have no conflict of interest.

Ethics Approval

The study was approved and supervised by the Ethics and Helsinki IRB committees of Tel Aviv University, Sheba Medical Center and Barzilai Medical Center, Israel.

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Leibovich-Nassi, I., Golander, H., Somech, R. et al. New Instrument for the Evaluation of Prodromes and Attacks of Hereditary Angioedema (HAE-EPA). Clinic Rev Allerg Immunol 61, 29–39 (2021). https://doi.org/10.1007/s12016-021-08843-8

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