title: A systematic review of definitions and reporting of bleeding outcome measures in haemophilia.
abstract: BACKGROUND
  Bleeding frequency is an important outcome commonly used in haemophilia studies. There is a variation in practice in how bleeding is measured and defined.
  
  
  OBJECTIVE
  The primary objective of this study was to determine how investigators define and report bleeding outcome measures.
  
  
  METHODS
  MEDLINE, EMBASE and the CENTRAL were searched from January 1990 to January 2014. We retrieved all published studies that included patients with haemophilia A or B and reported some measures of bleeding. Two reviewers independently performed title and abstract screening, full-text review and data abstraction of the identified studies.
  
  
  RESULTS
  A total of 118 studies fulfilled the inclusion criteria. Study designs were randomized controlled trials (RCT; 14%), cohort (68%), cross-sectional (5%) and others design (11%). The median duration of follow-up (Q1, Q3) was 20 (7.9, 50) months. We found 10 different bleeding outcomes reported [absolute number of bleeding 60 (50.8%) studies, annualized bleeding rate 60 (50.8%) studies, bleed per month 10 (8.5%) studies and others 11 (9.3%) studies]. Of these, 32 (27%) studies reported only mean or median without dispersion and 33 (28%) studies did not report any measures of central tendency (dispersion).
  
  
  CONCLUSIONS
  There is substantial variation in definitions and measures of bleeding outcomes in the haemophilia literature. This creates difficulty and limitations in comparing the outcomes between studies and in performing meta-analysis. The haemophilia research community needs to develop a consensus on a clear definition of bleeding and how to address the limitations associated with variations in measures of bleeding between centres and studies.
authors.affiliation: Department of Medicine, McMaster University, Hamilton, ON, Canada.|Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
authors.forename: C
authors.identifier: http://orcid.org/0000-0001-7209-9722
authors.initials: C
authors.lastname: Chai-Adisaksopha
authors.affiliation: Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Hillis
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.|Biostatistics Unit, St Joseph's Healthcare - Hamilton, Hamilton, ON, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Thabane
authors.affiliation: Department of Medicine, McMaster University, Hamilton, ON, Canada.|Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
authors.forename: A
authors.identifier: http://orcid.org/0000-0002-3331-8766
authors.initials: A
authors.lastname: Iorio
mesh_terms: D006467:Hemophilia A / Q000150:complications*; D002836:Hemophilia B / Q000150:complications*; D006470:Hemorrhage / Q000150:complications*; D006801:Humans; D012107:Research Design
keywords: haemarthrosis; haemophilia A; haemophilia B; haemorrhage; review