Outcome measures in Haemophilia: Beyond ABR (Annualized Bleeding Rate)

Abstract

Options for management of haemophilia are increasing rapidly with completely novel therapeutic approaches that cannot be compared using traditional factor assays. In addition, as prophylaxis regimens have improved, bleeding rates have decreased, and consequently, it is difficult to show an impact of novel therapies on rates of spontaneous bleeding. There is currently an urgent need for a panel of outcome measures to compare therapies that are dissimilar in many essential ways. Conventional objective outcome measures including joint physical examination and joint imaging continue to hold a central importance. Factor assays are essential for evaluation of products derived from native factor genes, but are not applicable to some extended half-life factors or non-factor bypassing agents. Global assays including thrombin generation and chromogenic assays of factor X activation are under investigation for their usefulness in haemophilia assessment. Bleeding rate is a conventional subjective patient-reported outcome that, while decreasing in frequency, is indispensable as an outcome given that the primary manifestation of haemophilia is bleeding. Other patient-reported outcomes such as pain intensity and interference, health-related quality of life and activities and participation are increasingly important to distinguish superior outcomes in comparative trials. This review of outcome measures for haemophilia presents examples of existing outcome measures with an emphasis on their strengths and limitations.

Keywords: haemophilia; haemostasis assays; joint disease; outcome measures; patient-reported outcomes.