Development of the US English version of the phenylketonuria – quality of life (PKU-QOL) questionnaire

Jurecki et al. Health and Quality of Life Outcomes (2017) 15:46 DOI 10.1186/s12955-017-0620-1 RESEARCH Open Access Development of the US English version of the phenylketonuria – quality of life (PKU-QOL) questionnaire Elaina Jurecki1, Amy Cunningham2, Vanessa Birardi1, Grégory Gagol3 and Catherine Acquadro4* Abstract Background: Phenylketonuria (PKU) is a rare genetic disorder caused by a defect in the metabolism of phenylalanine (PHE) resulting in elevated blood and brain PHE levels, and leading to cognitive, emotional, and psychosocial problems. The phenylketonuria – quality of life (PKU-QOL) questionnaire was the first self-administered disease-specific instrument developed to assess the impact of PKU and its treatment on the health-related quality of life (HRQL) of patients and their caregivers. Available in four versions (child, adolescent, adult and parent), the PKU-QOL was simultaneously developed and validated in seven countries [i.e., France, Germany, Italy, The Netherlands, Spain, Turkey and the United Kingdom (UK)]. The objectives of our study were to develop and linguistically validate the PKU-QOL questionnaire for use in the United States (US). Methods: The UK versions served as a basis for the development of the US English PKU-QOL questionnaire. The linguistic validation process consisted of 4 steps: 1) adaptation of the UK versions into US English by a translator native of US English and living in the US; 2) a clinician review; 3) cognitive interviews with patients and caregivers to test the appropriateness, understandability and clarity of the US translations; and 4) two proof-readings. Results: The adaptation from UK to US English revealed the usual syntactic and idiomatic differences between the two languages, such as differences in: 1) Spelling, e.g., “dietician” (UK) vs. “dietitian” (US), or “mum” (UK) vs. “mom” (US); 2) Syntax or punctuation; and 3) Words/expressions use, e.g., “holidays” (UK) vs. “vacation” (US), or “biscuits” (UK) vs. “crackers” (US). The major issue was cultural, and consisted of using a different terminology to describe PKU treatment throughout the questionnaires. The clinician, with the patients and the caregivers, during the interviews suggested to replace “supplement and amino-acid mixture” or “supplements” with “medical formula.” This wording was later changed to “medical food” to be consistent with the terminology used in current US published guidelines. Conclusions: The translation of the UK English PKU-QOL questionnaire into US English did not raise critical semantic and cultural issues. The PKU-QOL will be valuable for US healthcare providers in individualizing treatment and managing patients with PKU. Keywords: Phenylketonuria, PKU-QOL questionnaire, Health-related quality of life, Translation, Linguistic validation * Correspondence: 4 Mapi Research Trust, 27 rue de la Villette, Lyon 69003, France Full list of author information is available at the end of the article © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Jurecki et al. Health and Quality of Life Outcomes (2017) 15:46 Background Phenylketonuria (PKU), or phenylalanine hydroxylase deficiency (PAHD), is a rare autosomal recessive disease, induced by the deficiency of the hepatic enzyme, phenylalanine hydroxylase (PAH) that converts the essential amino acid phenylalanine (PHE) into tyrosine (TYR) [1]. This defect results in increased blood concentrations of PHE and toxic accumulation in the brain, leading to cognitive deficiencies, emotional disturbance and psychosocial disabilities [1, 2]. Current treatment for PKU includes a life-long diet highly restrictive in PHE that excludes high protein foods, and is supported nutritionally with medical foods [3] with the goal of maintaining blood PHE in the range of 120–360 μmol/l [3]. Medical foods for PKU provide the amino acids required for normal growth and development, without PHE or with negligible amounts of PHE, and include conditionally essential TYR and varying quantities of carbohydrate, fat, vitamins, and minerals [4, 5]. Pharmacological treatment with sapropterin dihydrochloride (KUVAN® BioMarin Pharmaceutical Inc., Novato, CA) is to date the only Food and Drug Administration (FDA) approved medication indicated for the treatment of PKU in conjunction with a PHE-restricted diet in individuals with tetrahydrobiopterin (BH4)-responsive PKU [3, 6]. Although the mechanism of action underlying the BH4 therapeutic effect is not entirely understood, it is thought that the primary mechanism-ofaction for BH4 treatment in PKU is the activation of residual PAH enzyme resulting in increased PHE oxidation to TYR [7, 8]. Research suggests that approximately 50% of PKU patients in the US could exhibit a beneficial response to BH4 [9]. The PHE-restricted diet can be burdensome to individuals with PKU and their families, leading to a risk of non-adherence with treatment, especially in adolescents and young adults [10–13]. Obstacles to treatment adherence include time constraints and stress associated with food preparation and record keeping, as well as restrictions imposed on social life. In addition, medical foods and specialty low protein foods may be poorly accepted and can impose a financial burden [11]. Diminishing adherence with age is a global issue. In a study surveying ten European centers, Ahring et al. [14] showed blood PHE control and the percentages of blood PHE concentrations within each center’s local and national target ranges diminished for patients above 16 years of age. Psychological and neurocognitive problems may be observed in individuals with PKU [15]. In a systematic literature review [16], Enns et al. reported that overall intellectual functioning and specific neuropsychological abilities may be suboptimal in patients treated with diet only and having either high or fluctuating blood PHE concentrations. They described executive dysfunction in working memory, conceptual reasoning, mental Page 2 of 6 flexibility and organizational strategy. Attentional problems leading to negative impacts on academic progress, as well as on self-esteem and emotional development, were noted. Regarding the evaluation of quality of life (QOL), Enns et al. described contrasting results. Out of six studies reviewed, two presented optimal outcomes, i.e., QOL comparable to normal controls [17, 18] and four reported suboptimal results [19–22]. However, more recent st (...truncated)