A systematic review of definitions and reporting of bleeding outcome measures in haemophilia

INTRODUCTION: Bleeding frequency is an important outcome commonly used in haemophilia studies. There is a variation in practice in how bleeding is measured and defined. AIM: 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.