Outcome measures for adult and pediatric hemophilia patients with inhibitors

Abstract

Recent advancements in almost all aspects of hemophilia treatment have vastly improved patient care and management, and new and emerging treatments hold the promise of further progress. However, there remains a scarcity of data on long-term outcomes in hemophilia, particularly among those patients with inhibitors, for whom no validated outcome assessment tools are currently available. At the 15 th ZürichHaemophilia Forum, an expert panel reviewed the most important outcome measures in inhibitor patients and considered the challenges associated with assessing outcomes in this population. A framework for outcome assessment in inhibitor patients incorporates traditional hemophilia outcome measures, such as bleed frequency and mortality, alongside measures of health, functioning, disability, social participation, quality of life, and economic considerations. It is important to remember that inhibitor patients differ in their clinical needs, perspectives, and priorities according to age, inhibitor status, degree of joint disease, and activity levels; as a result, the relative importance of different outcome measures will change throughout an inhibitor patient's life.Challenges inherent in measuring long-term outcomes in inhibitor patients include the small number of known patients, the subjective nature of many outcome assessment tools, and the risk of overburdening patients with repeated requests to complete questionnaires or participate in studies. Therefore, there is an urgent need to reach | HERMANS Het Malconsensus on the most important and appropriate assessment tools for measuring outcomes in this population. These tools should ideally be standardized, easily applied, and internationally applicable in order to collect and generate quality outcome data.

Annual Bleeding Rates: Pitfalls of Clinical Trial Outcomes in Hemophilia Patients

“…In addition, there is ongoing discussion about the optimal outcome measure and suitability of ABR as an efficacy measure in patients with hemophilia with and without inhibitors. [11][12][13][14][15] In the European Medicine Agency (EMA) guidelines on core summary of product characteristics for human plasma derived and recombinant coagulation factor FVIII and FIX products, it is stated that ABR is not comparable between different factor concentrates and between different clinical studies. 16,17 This statement has been introduced empirically based on the long-standing experience in the regulation of hemophilia therapeutics, however, there is lack of supportive and published evidence.…”

“…It has been demonstrated that there is a substantial range of bleeding frequencies among patients with similar clotting factor levels, confirming the ABR as a more personalized parameter. In addition, there is ongoing discussion about the optimal outcome measure and suitability of ABR as an efficacy measure in patients with hemophilia with and without inhibitors 11–15 . In the European Medicine Agency (EMA) guidelines on core summary of product characteristics for human plasma derived and recombinant coagulation factor FVIII and FIX products, it is stated that ABR is not comparable between different factor concentrates and between different clinical studies 16,17 .…”

Defining patient value in haemophilia care

“…Already, an abundance of tools exists to measure a variety of outcomes, such as joint health status, 13 QoL, 14 activities and participation, 13,15 as well as outcomes specifically for people with inhibitors. 16 However, the quality of these tools differs as well as their availability and applicability globally. 14,15 Therefore, standardization of which tools to use is being advocated.…”

“…Then, these outcomes should be measured appropriately. Already, an abundance of tools exists to measure a variety of outcomes, such as joint health status, QoL, activities and participation, as well as outcomes specifically for people with inhibitors . However, the quality of these tools differs as well as their availability and applicability globally .…”

Cross-Sectional and Longitudinal Construct Validity of the Generic KINDL-A(dult)B(rief) Questionnaire in Adults with Thrombophilia or with Hereditary and Acquired Bleeding Disorders

“…Furthermore, disease-specific questionnaires do not easily allow comparisons between population-based health measures or population-wide health assessments, and they can impede the conduct of comparative cost-benefit and cost-effectiveness analyses [11]. In such situations or when comparisons with patients with other disorders are warranted [12], generic HRQoL measures may add useful information to or partially replace disease-specific health measures. But generic health status measures also have limitations when applied to longitudinal research involving different age groups, especially when studying longitudinal changes of HRQoL through childhood and adolescence into adulthood.…”