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.

Generic PROMIS item banks in adults with hemophilia for patient‐reported outcome assessment: Feasibility, measurement properties, and relevance

“…Table 2 presents data on the number of items and floor and ceiling effects of the nine Dutch PROMIS item banks. The mean number of questions answered per CAT item bank varied from 5.2 (range, [3][4][5][6][7][8][9][10][11][12] for satisfaction with participation to 8.7 (range, 5-12) for anxiety.…”

“… 1 Appropriate patient‐reported outcomes are essential to evaluate these and novel interventions in individual patients and should cover the wide range of consequences of hemophilia. 6 …”

“…1 Appropriate patient-reported outcomes are essential to evaluate these and novel interventions in individual patients and should cover the wide range of consequences of hemophilia. 6 Patient Reported Outcomes Measurement Information System (PROMIS) is a set of universal, person-centered item banks that evaluates and monitors physical, mental, and social health in adults and children, currently available in many languages (eg, English, Dutch, German, Spanish, French, Hebrew, Chinese, and Korean). 7 Other than Classical Test Theory (CTT)-based legacy instruments like the Haemophilia Activities List (HAL) and RAND-36, with sum and component scores that are a sum of all individual ordinal items of the questionnaire, PROMIS item banks were developed according to the Item Response Theory (IRT).…”

Variability of treatment modalities and intensity in patients with severe haemophilia A on prophylaxis: Results from the Italian national registry

“…In addition to age, we need data on body weight, bleeding pattern, status of the musculoskeletal system, intensity and timing of physical activity, coagulation factor pharmacokinetic, targeted trough level and age (with inherent different individual FVIII pharmacokinetic). Furthermore, defining the outcomes (eg bleeding rate, joint physical examination, quality of life) 31 and the related variables necessary to assess the quality and value of care is even more fundamental. This process of outcomes’ and variables’ definition requires an action by the haemophilic clinical and scientific community; whilst the development of a tool necessary to register these variables, assessing the value produced and the changes over time can be developed by improving the available Italian NRCC established at the ISS (Decree of March 3, 2017 “Identification of surveillance systems and registries of mortality, cancer and other diseases”) and the other registries in use at the Italian HTCs that have been developed with different aims compared to the value‐based healthcare approach that we are suggesting.…”

Enhanced Half-Life Recombinant Factor VIII Concentrates for Hemophilia A: Final Results from Extension Studies

“…In the frame of a multidisciplinary approach to hemophilia care, it should be mandatory to improve outcome assessment going beyond ABR and consumption data, also considering imaging, functional, and patient-reported outcomes. 8…”