PRO72 DEVELOPMENT OF CONCEPTUAL FRAMEWORKS AND PILOT PRO MEASURES IN OTC DEFICIENCY

Abstract

Ornithine transcarbamylase deficiency (OTC) is a rare inborn error of metabolism that results in high ammonia blood levels and symptoms of confusion, vomiting, coma, and consequently cognitive functioning impairments. The objective of this research was to develop preliminary conceptual models and draft patient-reported outcome (PRO) measures for OTC deficiency using available literature, key opinion leader (KOL) interview data, and available patient interview data. A focused literature review was conducted via Medline® to identify clinician- and patient-reported signs, symptoms, and impacts of OTC. Key opinion leaders for clinician interviews were identified by the study sponsor. Following ethics approval, patients with OTC were recruited for interviews using a recruitment flyer. Concepts were included or excluded from the conceptual frameworks based on pre-specified criteria. The conceptual frameworks were used to develop items for pilot PRO assessments. Subsequent patient interviews included a cognitive debrief of the PRO assessments. Three KOL interviews, two initial patient interviews, and three articles contributed to the development of the conceptual frameworks. The hypothesized symptoms conceptual framework includes eleven concepts (confusion, sudden change in feeling, difficulty focusing/paying attention, poor balance, loss of appetite, nausea, stomach pain, vomiting, tiredness, headache, and dizziness) within four domains (neurocognitive, gastrointestinal, energy-related, and other physical symptoms). The hypothesized impacts conceptual framework includes seven concepts (restricted diet, difficulty adhering to diet, fear of hyperammonemia events, feeling different from others, feeling embarrassed, low self-esteem, and receiving unwanted attention) within three domains (diet, emotional, and social). Symptom and impact pilot measures were developed using these concepts. Five additional cognitive interviews indicate that thus far the pilot measures are generally well understood and found clear by patients. The ongoing development strategy of the hypothesized conceptual frameworks and pilot PRO measures in OTC is an innovative approach to PRO development given the recruitment challenges faced in this rare disease.