Characterization of health outcomes in patients with hemophilia A and B: Findings from psychometric and health economic analyses

2018-07-26Hemophilia is a hereditary blood disorder characterized by deficiencies in coagulation factors VIII (hemophilia A) and IX (hemophilia B), which imposed significant disease burden on patients, caregivers, and the society. Bleeding is the most important clinical manifestation of hemophilia. Repeated bleeding into the joints leads to irreversible joint damage, impaired health outcomes, and increased health resource utilization. Over the past decades, hemophilia has been treated with factor replacement therapies which replenish the deficient coagulation factors through intravenous infusions on either prophylactic (or prophylaxis) or episodic (or on-demand) regimen. Prophylaxis administers factors regularly to prevent anticipated bleeding; on-demand regimen administers factors ""as-needed"", either after bleeding occurs or as extra doses to prevent breakthrough bleeding occurs at special events (e.g. sports). Prophylaxis has been recommend by the World Federation of Hemophilia as the optimal regimen to preserve joint function and increasingly practiced worldwide especially in children who would benefit most from early initiation of prophylaxis. ❧ Despite tremendous benefits associated with prophylaxis, the high costs and time-consuming nature of it may significantly reduce adherence, which is critical for successful management of hemophilia. Prior studies measure adherence using highly variable methods, underscoring the lack of gold standard measures of adherence in hemophilia research. One of the most widely used subjective measures is the Validated Hemophilia Regimen Treatment Adherence Scales - Prophylaxis (VERITAS-Pro), which is also the only standardized measure of adherence to prophylaxis. VERITAS-Pro is a patient-/parent-reported questionnaire which was developed in 2010 by researchers in the Indiana Hemophilia Treatment Center (IHTC) in the USA. The measure consists of 24 questions under 6 domains, and has been widely used and translated into more than 30 languages. However, VERITAS-Pro have not been fully examined for psychometric properties (i.e. construct validity, predictive validity, rating scale performance, and discriminative ability), which hindered its further applications and raised concerns about the credibility of studies using this measure. ❧ Another emerging issue in hemophilia research is the lack of studies examining health outcomes in adolescents and young adults with hemophilia, who are in transition from childhood to adulthood and experiencing composite clinical and psychosocial challenges not experienced by patients in other age groups. Adherence to prophylaxis was found to be the lowest among adolescents and young adults, however it is still unclear how much of an impact it will have on other important health outcomes such as bleeding and factor utilization. Although national policy makers have identified transition as a priority issue for patients with blood disorders, no studies have ever quantified the impact of transition from childhood to adulthood on health outcomes in hemophilia patients. ❧ My dissertation consists of three studies characterizing health outcomes in persons with hemophilia A and B, using data collected in the Hemophilia Utilization Group Studies (HUGS) in the USA. The first study (Chapter 2) assessed construct validity, rating scale performance, and discriminative ability for VERITAS-Pro and proposed a 18-item modified version (mVERITAS-Pro) with improved psychometric properties based on Rasch analysis. The second study (Chapter 3) found weak concurrent and predictive validities for VERITAS-Pro and mVERITAS-Pro with criterion measures calculated using factor prescription and dispensing records. The third study (Chapter 4) showed that transition from childhood to adulthood was associated with increased bleeding compared to childhood, and increased factor utilization compared to childhood and adulthood using a longitudinal analysis of hemophilia A patients. ❧ Altogether, findings from these studies provided important psychometric and health economic evidence for the characterization of health outcomes in patients with hemophilia A and B. More importantly, they shed light on areas for improvement regarding the measurement of adherence and unmet need in vulnerable hemophilia populations who are in transition from childhood to adulthood. Furthermore, methods developed and used in these studies can be applied in future research of hemophilia as well as other chronic conditions