OBJECTIVES: Ornithine transcarbamylase deficiency (OTC) is a rare inborn error of metabolism that directly results in high ammonia blood levels, leading to symptoms of confusion, vomiting, coma, and cognitive functioning impairments. The objective of this research was to develop disease-specific, content-valid patient-reported outcome measures (PROs) for use in OTC deficiency using a patient-centric outcomes assessment approach.

METHODS: Results from a targeted literature review, interviews with key opinion leaders, and concept elicitation interviews were used to develop draft conceptual models and questionnaires. Mixed concept elicitation and cognitive interviews were conducted to debrief the draft questionnaires. All interviews were conducted with English-speaking patients after IRB/ethics approval. Results from interviews were used to update the initial conceptual models and questionnaires.

RESULTS: The Hyperammonemia Indicator Questionnaire (HI-Q) was designed to collect patient-reported occurrences of symptoms of hyperammonemia, and the OTC Deficiency Impact Questionnaire (OTC-D-IQ) was designed to collect patient-reported diet, emotional, physical, and sleep-related impacts of OTC deficiency. Ten mixed concept elicitation and/or cognitive interviews were conducted with adolescent (n=2) and adult (n=8) participants to debrief the adolescent and adult version of the measures. Additionally, one child aged eight participated in an interview to debrief the child version of the measures. Despite the small sample size for child participants, results were still considered in conjunction with the adolescent/adult results to inform measure revisions. Overall, the instructions, items, and response options for the HI-Q and OTC-D-IQ were interpreted as intended and reported to be clear and relevant. Several new concepts were identified for inclusion in the OTC-D-IQ.

CONCLUSIONS: These PRO measures were developed with the PRO Guidance in mind and incorporated the flexibility encouraged by the FDA’s rare disease guidance. The OTC HI-Q and OTC-D-Q are the only measures developed and tested for use in this population. Future research includes psychometric evaluation of and corresponding revisions to the measures.