Study design
A new PRO instrument: HAE Evaluation of Prodromes and Attacks (HAE-EPA) was utilized in this study to assess patient reports. Its description and validation process is detailed elsewhere.13 This instrument consists of personal and health-related data, evaluation of prodromes and evaluation of attacks, and was powered to collect and analyze recent prodrome/attack data from the participating patients.
For practical purposes, we chose to describe the range of signs and symptoms ocurring in each body system relevant to HAE (domain) as a ’cluster’.11,12 Accordingly, ’abdominal cluster’ represented all the recognizable gastrointestinal (GI) signs and symptoms reported by the patients (i.e. nausea, vomiting, abdominal pains, diarrhea etc.). This method has proven useful and easy to comprehend by both patients and investigators, and is also amenable to statistical analysis.10-13 Most relevant clusters in this study included: facial, oropharyngeal, abdominal, extremities (skin and subcutaneous tissue) and urogenital domains.. Each cluster of the involved body location is evaluated by specific items, adapted to its unique charachteristics (i.e. abdominal cluster-9 items, Facial-4, urogenital-7, oropharyngeal-8, Extremities-3). Each cluster’s involvement was represented by four scalable dimensions, measured by a visual analog score (Likert scale, VAS): pain (scaled), severity (i.e. degree of swelling), impairment (i.e. interference with daily activities) and functionality (i.e. use of a limb).