title: Development and content validity testing of a patient-reported outcomes questionnaire for the assessment of hereditary angioedema in observational studies.
abstract: BACKGROUND
  Hereditary Angioedema (HAE), a rare genetic disease, manifests as intermittent, painful attacks of angioedema. Attacks vary in frequency and severity and include skin, abdominal and life-threatening laryngeal swellings. This study aimed to develop a patient reported outcome (PRO) tool for the assessment of HAE attacks, including their management and impact on patients' lives, for use in clinical studies, or by physicians in general practice.
  
  
  METHODS
  The results of open-ended face to face concept elicitation interviews with HAE patients in Argentina (n = 10) and the US (n = 33) were used to develop the first draft questionnaire of the HAE patient reported outcomes questionnaire (HAE PRO). Subsequently, in-depth cognitive debriefing interviews were performed with HAE patients in the UK (n = 10), Brazil (n = 10), Germany (n = 11) and France (n = 12). Following input from eight multinational clinical experts further cognitive interviews were conducted in the US (n = 12) and Germany (n = 12). Patients who experienced abdominal, cutaneous or laryngeal attacks of varying severity levels were included in all rounds of interviews. Across the rounds of interviews patients discussed their HAE attack symptoms, impacts and treatments. Cognitive debriefing interviews explored patient understanding and relevance of questionnaire items. All interviews were conducted face to face following a pre-defined semi-structured interview guide in the patient's native language.
  
  
  RESULTS
  Patients reported a variety of HAE symptoms, attack triggers, warning signs, attack impacts and treatment options which were used to develop the HAE PRO. The HAE PRO was revised and refined following input from patients and clinical experts. The final 18-item HAE PRO provides an assessment of the HAE attack experience including symptoms, impacts, treatment requirements, healthcare resource use and loss of productivity caused by HAE attacks.
  
  
  CONCLUSIONS
  Patient and expert input has contributed to the development of a content valid questionnaire that assesses concepts important to HAE patients globally. HAE patients across cultures consider the HAE PRO a relevant and appropriate assessment of HAE attacks and treatment.
authors.affiliation: Adelphi Values, Adelphi Mill, Bollington, Cheshire, UK. Nicola.Bonner@adelphivalues.com.
authors.forename: Nicola
authors.initials: N
authors.lastname: Bonner
authors.affiliation: Adelphi Values, Adelphi Mill, Bollington, Cheshire, UK. linda.abetz-webb@p-coa.com.
authors.forename: Linda
authors.initials: L
authors.lastname: Abetz-Webb
authors.affiliation: Shire International GmbH, Zug, Switzerland. lrenault@shire.com.
authors.forename: Lydie
authors.initials: L
authors.lastname: Renault
authors.affiliation: University Hospital, La Paz, Hospital La Paz Institute for Health Research (IdiPaz), Biomedical Research Network on Rare Diseases-U754 (CIBERER), Madrid, Spain. mteresa.caballero@idipaz.es.
authors.forename: Teresa
authors.initials: T
authors.lastname: Caballero
authors.affiliation: Department of Immunology, Barts Health NHS Trust, London, UK. hilary.longhurst@bartshealth.nhs.uk.
authors.forename: Hilary
authors.initials: H
authors.lastname: Longhurst
authors.affiliation: Department of Dermatology and Allergy, Allergie-Centrum-Charité, Charité - Universitätsmedizin Berlin, Berlin, Germany. Marcus.Maurer@charite.de.
authors.forename: Marcus
authors.initials: M
authors.lastname: Maurer
authors.affiliation: Medicine Division Allergy/ Immunology and US HAEA Angioedema Center, University of California, San Diego, CA, USA. scchristiansen@ucsd.edu.
authors.forename: Sandra
authors.initials: S
authors.lastname: Christiansen
authors.affiliation: Department of Medicine, Division of Rheumatology, Allergy and Immunology, UC San Diego School of Medicine, San Diego, CA, USA. bzuraw@ucsd.edu.|San Diego Veterans Hospital, San Diego, CA, USA. bzuraw@ucsd.edu.
authors.forename: Bruce
authors.initials: B
authors.lastname: Zuraw
mesh_terms: D000328:Adult; D000368:Aged; D054179:Angioedemas, Hereditary / Q000175:diagnosis* / Q000523:psychology*; D001118:Argentina; D001938:Brazil; D005260:Female; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D063868:Patient Outcome Assessment; D011594:Psychometrics; D011788:Quality of Life / Q000523:psychology*; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D006113:United Kingdom; D014481:United States; D055815:Young Adult