Economic evaluations of hemophilia A interventions in Canada

Abstract

BACKGROUND: Hemophilia A is an X-linked disorder defined by a lack of clotting factor VIII within the blood. The current standard of care for hemophilia A is prophylaxis through injection of clotting factors. There are many varieties of clotting factors currently available on the Canadian market including standard half-life, extended half-life, non-factor replacement proteins, and second-generation extended half-life options. No matter what option is chosen, the cost is extremely high, primarily due to the cost of clotting factors, which have been cited as representing over 92% of the cost of hemophilia A treatment. For decades, gene therapy has been in development for those with hemophilia A. So far, none have been approved for use in Canada. Gene therapy is expected to last for at least 5 years without requiring supplemental injections. Gene therapy has an incredibly high short-term cost. Health technology assessments can be used to evaluate the cost-effectiveness of a treatment. There is currently no hemophilia A gene therapy cost-effectiveness study in the Canadian context. OBJECTIVE: The objective of this thesis was to analyze the economic environment of hemophilia A interventions in Canada and to determine if gene therapy would be cost-effective. This thesis completed 1) a population-level retrospective study on health utilities, 2) an economic analysis of the existing prophylaxis options, 3) a healthcare system cost analysis, 4) a narrative review on the diagnosis and treatment pathway for women with hemophilia A, and 5) cost-effectiveness analysis for hemophilia A gene therapy for men in Canada including re-dosable gene therapy. METHODS: Health utilities were retrieved from the Canadian Bleeding Disorders Registry (CBDR) and were analyzed with a multivariable regression model. A microsimulation model was built to analyze the cost-effectiveness of the currently available options (SHL, EHL, non-factor protein, second generation EHL). Healthcare system resource use costs were determined through health administrative data analysis. The microsimulation model was expanded allowing for the inclusion of gene therapy and the dynamics were analyzed. An incremental cost-effectiveness ratio (ICER) value comparing gene therapy to multiple methods of prophylaxis was computed and the most cost-effective treatment was identified. RESULTS: The feasibility study demonstrated, in a perfect scenario, gene therapy could be cost-effective in Canada. The feasibility study also highlighted significant sensitivity to cost and utility data. The population-based, cross-sectional study of health utilities provided the average utility values (and standard deviations) for patients with hemophilia A in Canada 0.79 (0.17), 0.76 (0.20), and 0.77 (0.19) for patients with severe, moderate, and mild hemophilia. The study of health utilities also illustrated that chronic pain was a significant factor in lowered hemophilia A utility. The economic evaluation of modern prophylaxis interventions demonstrated that to be dominant in the Canadian market EA would require a 50% price reduction, even though it significantly improved long-term joint health outcomes. The population-level retrospective study of healthcare costs in Ontario demonstrated, even with hemophilia treatment, there remains an increased healthcare system cost for those living with hemophilia A, regardless of sex. The narrative review on the experiences of women and girls with hemophilia demonstrated that barriers to diagnosis and care remain, and further research is necessary to determine how best to address these barriers. The economic analysis of gene therapy identified very similar outcomes in terms of life-expectancy and utility values to emicizumab. At current list prices, gene therapy has similar quality-adjusted life years to emicizumab and costs ~350K CAD more over a lifelong time horizon. With a 7.5 % price reduction, gene therapy may become the dominant strategy. CONCLUSION/IMPLICATIONS: This provides more insight to decision-makers on whether gene therapy should be reimbursed for hemophilia A patients in Canada while providing a deeper understanding of the health burden of hemophilia A in Canada.