Dataset Information

Measuring Burden of Illness in Phenylketonuria (PKU): Development of the PKU Symptom Severity and Impacts Scale as a Robust Patient-Reported Outcome.

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.

SUBMITTER: Quinn J

PROVIDER: S-EPMC8684342 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPhenylketonuria (PKU) is an inherited deficiency in the enzyme phenylalanine hydroxylase (PAH), which, when poorly-managed, is associated with clinical features including deficient growth, microcephaly, seizures, and intellectual impairment. The management of PKU should start as soon as possible after diagnosis to prevent irreversible damage and be maintained throughout life. The aim of this study was to assess the burden of illness in PKU patients in general and in PKU patients born before and after the introduction of newborn screening in Germany.MethodsThis retrospective matched cohort analysis used the Institut für angewandte Gesundheitsforschung Berlin (InGef) research database containing anonymized healthcare claims of approximately 4 million covered lives. PKU patients were compared with matched controls from the general population within the same database (1:10 ratio via direct, exact matching on age and gender without replacement). PKU patients were included if they were aged ?18?years on 01/01/15 and were continuously enrolled from 01/01/10 to 31/12/15. The 50 most commonly reported comorbidities and 50 most commonly prescribed medications in the PKU population were analyzed. Differences between groups were tested using 95% confidence interval (CI) of prevalence ratio (PR) values.ResultsThe analysis included 377 adult PKU patients (<?5 of which were receiving sapropterin dihydrochloride) and 3,770 matched controls. Of the 50 most common comorbidities in the PKU population, those with a statistically significant PR?>?1.5 vs controls included major depressive disorders (PR?=?2.3), chronic ischemic heart disease (PR?=?1.7), asthma (PR?=?1.7), dizziness and giddiness (PR?=?1.8), unspecified diabetes mellitus (PR?=?1.7), infectious gastroenteritis and colitis (PR?=?1.7), and reaction to severe stress and adjustment disorders (PR?=?1.6). The most commonly prescribed Anatomical Therapeutic Chemical (ATC) subcodes among PKU patients (vs the control population) are for systemic antibacterials (34.7% vs 32.8%), anti-inflammatory and antirheumatic (29.4% vs 27.5%), renin-angiotensin agents (30.0% vs 27.0%), acid-related disorders (29.4% vs 20.2%), and beta-blockers (24.9% vs 19.9%).ConclusionThe overall clinical burden on patients with PKU is exacerbated by a significantly higher risk of numerous comorbidities and hence, prescribing of the requisite medication, both for recognized (e.g. major depressive disorders) and more unexpected comorbidities (e.g. ischemic heart disease).