Abstract
INTRODUCTION: Phenylketonuria (PKU) is a rare, metabolic genetic disorder that can cause various neuropsychological symptoms that often affect patients' health-related quality of life, even for patients with good metabolic control. To date, no patient-reported outcomes (PRO) instrument combines the measurement of neuropsychological and dietary concepts to capture the broad impact of PKU on quality of life. This article presents the development of the PKU Symptom Severity and Impacts Scale (PKU-SSIS), a PRO instrument that is designed to evaluate neuropsychological symptoms and impacts in early-treated patients with PKU. METHODS: A draft instrument was developed based on a targeted literature review, PKU expert physician interviews, and an advisory board consisting of patients with PKU. Qualitative interviews combining concept elicitation/cognitive interviews were conducted with patients with classic PKU aged at least 15 years old. A separate sample of 20 patients with PKU completed the draft PKU-SSIS in a paper survey format, to enable preliminary assessment of any floor and ceiling effects. RESULTS: Patient interviews elicited four key symptom themes: neurocognitive function, emotional and behavioral, physical functioning, and physical health. Four impact themes were also identified: social function, physical health, emotions, and level of independence. No floor or ceiling effects were identified. CONCLUSION: The final instrument included 22 items, covering three symptom domains (1. emotional, mood, and psychological; 2. (neuro)cognitive, executive, and intellectual function; and 3. physical health), and four impact domains (1. social relations, 2. level of independence, 3. general well-being, and 4. self-care). The PKU-SSIS will help to address an important gap in the evaluation of existing and future treatments for PKU.