OBJECTIVES: This study investigates factors influencing reimbursement for innovative therapies targeting rare bleeding disorders (RBDs). It explores the interplay between clinical development, regulatory approval, health technology assessments (HTAs), and payer perspectives to understand their impact on reimbursement decisions.

METHODS: A mixed-methods approach was used, employing a thematic framework to examine clinical trial outcomes, cost-effectiveness, comparative effectiveness, unmet needs, and study design limitations. HTA reports from England, Scotland, France, Germany, and Canada were systematically retrieved on conditions such as atypical hemolytic uremic syndrome, acquired/idiopathic thrombotic thrombocytopenic purpura, paroxysmal nocturnal hemoglobinuria, hemophilia A, and von Willebrand disease. Unrelated conditions and evaluations, such as polycythemia vera, beta-thalassemia-associated anemia, and anticoagulants reversal, were excluded to maintain a focused analysis on RBDs.

RESULTS: Preliminary findings identified several factors influencing reimbursement outcomes. Positive trial results (e.g., ravulizumab, pegcetacoplan, emicizumab) were pivotal to secure reimbursements. Demonstrating noninferiority or superiority to existing therapies was essential, but uncertainty due to lack of head-to-head trials hindered approvals (e.g., fostamatinib, caplacizumab). Therapies targeting clinical endpoints (e.g., ravulizumab, emicizumab) were more likely reimbursed than those relying on surrogate endpoints (e.g., romiplostim). Poor study design, including issues with real-world evidence and the identification of suitable comparators (e.g., fostamatinib, eculizumab), was linked to negative recommendations. High costs posed significant barriers; effective treatments like eculizumab required substantial price reductions to secure reimbursement. Patient access schemes (PASs) and cost-minimization measures (e.g., eltrombopag) positively influenced decisions. Addressing specific patient needs (e.g., less frequent dosing, reduced transfusions) improved HTA outcomes (e.g., pegcetacoplan, ravulizumab).

CONCLUSIONS: Robust study designs and targeting clinical endpoints improve the chances of positive reimbursement outcomes. High costs often pose barriers, but PASs and cost-minimization measures can positively influence decisions. Continued HTA methods advancements, like CDA-AMC's "Time-Limited Reimbursement Recommendations", could enhance accessibility and affordability of these therapies, ensuring timely and effective treatment for patients with RBDs.