title: Content validity of visual analog scales to assess symptom severity of acute angioedema attacks in adults with hereditary angioedema: an interview study.
abstract: BACKGROUND
  Hereditary angioedema (HAE) is a rare, debilitating, potentially life-threatening condition characterized by recurrent acute attacks of edema of the skin, face/upper airway, and gastrointestinal and urogenital tracts. During a laryngeal attack, people with HAE may be at risk of suffocation, while other attacks are often associated with intense pain, disfigurement, disability, and/or vomiting. The intensity of some symptoms is known only to the person experiencing them. Thus, interview studies are needed to explore such experience and patient-reported outcome measures (PROMs) are required for systematic assessment of symptoms in the clinical setting and in clinical trials of treatments for acute HAE attacks.
  
  
  OBJECTIVE
  The aim of this interview study was to assess the content validity and suitability of four visual analog scale (VAS) instruments for use in clinical studies. The VAS instruments were designed to assess symptoms at abdominal, oro-facial-pharyngeal-laryngeal, peripheral, and urogenital attack locations. This is the first known study to report qualitative data about the patient's experience of the rare disorder, HAE.
  
  
  METHODS
  Semi-structured exploratory and cognitive debriefing interviews were conducted with 27 adults with a confirmed clinical/laboratory diagnosis of HAE (baseline plasma level of functional plasma protein C1 esterase inhibitor [C1INH] <50% of normal without evidence for acquired angioedema). There were 17 participants from the US and 10 from Italy, with mean age 42.5 (SD 14.5) years, range 18-72 years, mean HAE duration 21.3 (SD 14.1) years, range 1-45 years, 67% female, and 44% VAS-naïve. Experience of acute angioedema attacks was first explored, noting spontaneous mentions by participants of HAE symptomatology. Cognitive debriefing of the VAS instruments was undertaken to assess the suitability, comprehensibility, and relevance of the VAS items. Asymptomatic participants completed the VAS instruments relevant to their angioedema experience, reporting as if they were experiencing an acute angioedema attack at the time. Interviews were conducted in the clinic setting in the US and Italy over an 8-month period.
  
  
  RESULTS
  Participants mentioned spontaneously almost all aspects of acute angioedema attacks covered by the four VAS instruments, thus providing strong support for inclusion of nearly all VAS items, with no important symptoms missing. Predominant symptoms found to be associated with acute angioedema attacks were edema and pain, and there was evidence of varying degrees of disruption to everyday activities supporting the inclusion of an overall severity item reflecting the disabling effects of HAE symptoms. VAS item wording was understood by participants.
  
  
  CONCLUSIONS
  This interview study explored and reported the patient experience of HAE attacks. It demonstrated the content validity of the four anatomical location HAE VAS instruments and their suitability for use in clinical trials of recombinant human C1INH (rhC1INH) treatment for ascertaining trial participants' assessments of the severity of acute angioedema symptoms.
authors.affiliation: AHP Research, Hornchurch, UK. carolyn.mcmillan@ahpresearch.com
authors.forename: Carolyn Vivienne
authors.initials: CV
authors.lastname: McMillan
authors.forename: Jane
authors.initials: J
authors.lastname: Speight
authors.forename: Anurag
authors.initials: A
authors.lastname: Relan
authors.forename: Luca
authors.initials: L
authors.lastname: Bellizzi
authors.forename: Gerald
authors.initials: G
authors.lastname: Haase
authors.forename: Marco
authors.initials: M
authors.lastname: Cicardi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D054179:Angioedemas, Hereditary / Q000175:diagnosis* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007407:Interviews as Topic; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement / Q000379:methods*; D057240:Patient Preference; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult