Development and content validity testing of a patient-reported outcomes
questionnaire for the assessment of hereditary angioedema in observational
studies
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