title: Longitudinal changes in health-related quality of life for chronic diseases: an example in hemophilia A.
abstract: BACKGROUND
  Patients with well-managed rare chronic diseases such as hemophilia maintain a stable health state and health-related quality of life (HrQoL) that may be affected by acute events. Longitudinal HrQoL assessments analyzed using multivariate multilevel (MVML) modelling can determine the impact of such events on individuals (within-person effect) and identify factors influencing within-population differences (between-person effect).
  
  
  OBJECTIVE
  To demonstrate the application of MVML modelling in a longitudinal study of HrQoL in hemophilia A.
  Using data on 136 adults and 125 children from a two-year observational cohort study of burden of illness in US hemophilia A patients, MVML modelling determined the effect of time-invariant (sociodemographic and clinical characteristics) and time-varying factors (bleeding frequency, emergency room visits, and missed work/school days) on within-person and between-person HrQoL changes. HrQoL was assessed using the SF-12 health survey (adults) and PedsQL inventory (children) at baseline, then every 6 months.
  
  
  RESULTS
  In children, within-person (p < 0.0001) and between-person (p < 0.0001) psychosocial functioning was reduced by each additional bleed and missed day (within-person: p = 0.0089; between-person: p = 0.0060). Within-person physical functioning was reduced by each additional bleed (p < 0.0001), emergency room (ER) visit (p = 0.0284), and missed day (p = 0.0473). Between-persons, additional missed days (p < 0.0001) significantly decreased physical functioning. In adults, each additional missed day reduced SF-12 Health Survey mental (p = 0.0025) and physical (p = 0.0093) component summary scores. Each additional bleed also decreased physical component summary (PCS) significantly (p = 0.0093).
  
  
  CONCLUSIONS
  This study demonstrated the applicability of MVML modelling in identifying time-invariant and time-varying factors influencing HrQoL in a rare chronic disease population. Small but significant within-person and between-person changes in HrQoL with each additional acute event experienced were identified, which if frequent, could have a large cumulative impact. The results suggest that MVML modelling may be applied to future studies of longitudinal change in HrQoL in other rare chronic disease populations.
authors.affiliation: University of Southern California, School of Pharmacy, 1985 Zonal Ave, PSC 206-BE, Los Angeles, CA, 90089, USA, jiatlinp@usc.edu.
authors.forename: Jiat-Ling
authors.initials: JL
authors.lastname: Poon
authors.forename: Jason N
authors.initials: JN
authors.lastname: Doctor
authors.forename: Michael B
authors.initials: MB
authors.lastname: Nichol
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D006304:Health Status; D006467:Hemophilia A / Q000150:complications / Q000503:physiopathology* / Q000523:psychology*; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D015999:Multivariate Analysis; D011788:Quality of Life; D035583:Rare Diseases; D012959:Socioeconomic Factors; D013997:Time Factors; D055815:Young Adult