title: Measuring patient experiences in Fabry disease: validation of the Fabry-specific Pediatric Health and Pain Questionnaire (FPHPQ).
abstract: BACKGROUND
  Common symptoms for children with Anderson-Fabry Disease (FD) such as acroparaesthesia and gastrointestinal manifestations can only be objectively assessed in patients using a valid instrument. To date, no such instrument exists.
  
  
  METHODS
  A preliminary 40-item measure of symptoms and experience with FD, the Fabry-specific Paediatric Health and Pain Questionnaire (FPHPQ) was developed, but lacked a formal assessment of its measurement properties. The FPHPQ was used in the Fabry Outcome Survey (FOS), a registry for all patients with a confirmed diagnosis of FD who are receiving agalsidase alfa, or are treatment naïve and who are managed by physicians participating in FOS. After an item analysis to explore how items performed and combined into domains, a battery of psychometric analyses was performed to assess the measurement properties of this new instrument.
  
  
  RESULTS
  Eighty-seven children (ages 4-18 years) completed the questionnaire. Twenty-three items in three subscales of the questionnaire emerged: pain associated with heat or exertion, pain associated with cold, and abdominal pain and fatigue symptoms. Internal consistency reliability for all three subscales was good (Cronbach alpha ≥ 0.84). Reliability was equally high for all age groups (4-7, 8-12, and 13-18). Test-retest reliability was high for all three subscales (intraclass correlation coefficient ≥ 0.74). Construct validity was demonstrated by moderate correlation with brief pain inventory (BPI), KINDL, and EQ-5D. Known group validity showed all subscales were able to discriminate between Fabry disease severity groups as classified by above or below median of the FOS MSSI (Mainz Severity Score Index) grade. The heat or exertion subscale was responsive to change in symptoms between responders and non-responders as defined by change in EQ-5D index scores between the first and second visit.
  
  
  CONCLUSIONS
  Preliminary results indicate that the measurement properties of FPHPQ are valid and reliable for assessing patient-reported symptoms of FD. The questionnaire could be a useful tool for clinicians to understand the progression of disease and monitor treatment effects. FPHPQ will be further validated and refined as the FOS registry is continuously adding more patients.
authors.affiliation: The Willink Biochemical Genetics Unit, Genetic Medicine, St Mary's Hospital, Manchester, UK. Uma.ramaswami@cmft.nhs.uk
authors.forename: Uma
authors.initials: U
authors.lastname: Ramaswami
authors.forename: Donald E
authors.initials: DE
authors.lastname: Stull
authors.forename: Rossella
authors.initials: R
authors.lastname: Parini
authors.forename: Guillem
authors.initials: G
authors.lastname: Pintos-Morell
authors.forename: Catharina
authors.initials: C
authors.lastname: Whybra
authors.forename: Gisela
authors.initials: G
authors.lastname: Kalkum
authors.forename: Marianne
authors.initials: M
authors.lastname: Rohrbach
authors.forename: Mireia
authors.initials: M
authors.lastname: Raluy-Callado
authors.forename: Michael
authors.initials: M
authors.lastname: Beck
authors.forename: Wen-Hung
authors.initials: WH
authors.lastname: Chen
authors.forename: Ingela
authors.initials: I
authors.lastname: Wiklund
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D000795:Fabry Disease / Q000175:diagnosis / Q000523:psychology*; D005260:Female; D006801:Humans; D008297:Male; D010147:Pain Measurement; D011788:Quality of Life; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires / Q000592:standards*