Hemophilia Gene Therapy Value Assessment: Methodological Challenges and Recommendations.

Gene therapy for hemophilia is designed to produce health gains for patients over many years. Rewarding that value creation on the basis of a one-time treatment implies a large upfront cost. This cost can only be justified by long-term health benefits and being cost-effective compared with conventional treatments. Yet, uncertainties about the long-term benefits make it challenging to assess clinical and economic value of gene therapies at launch. We identify and discuss key methodological challenges in assessing the value of gene therapy for hemophilia, including the immaturity of evidence on the durability of benefits, lack of definition and valuation of cure for chronic diseases, absence of randomized controlled trials, limitations of traditional quality of life measures in hemophilia, approach for qualifying cost-savings compared with current treatments, and choice of perspective. The Institute for Clinical and Economic Review has developed a framework for assessing single or short-term therapies (ICER-SST) and has applied it in hemophilia. After reviewing this framework and its application, we recommend the following when assessing the value of hemophilia gene therapies: (1) leveraging expert clinical opinion to justify assumptions on the durability of benefits; (2) using external synthetic controls and lead-in, self-controlled trials to assess comparative effectiveness; (3) addressing limitations of traditional quality of life measures through the use of modified utility collection approaches; (4) adjusting cost offsets from gene therapies with caution; (5) considering outcome-based contracting to address uncertainties about prices and long-term outcomes; and (6) presenting societal and healthcare system perspectives in parallel.

Managed care interventions for improving outcomes in acute heart failure syndromes.

Acute heart failure syndromes (AHFS) are characterized by a gradual or rapid progression of the signs and symptoms of heart failure (HF), resulting in a need for urgent therapy. Patients with AHFS comprise approximately 20% of all HF patients and represent the most severely ill and undermanaged subpopulation of patients with HF. Despite the rising prevalence and costs associated with AHFS, the disease remains largely undermanaged, partially as a result of a failure to initiate treatment with proven therapies, such as beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers, during hospitalization or soon after discharge. Although professional organizations have been striving to improve the state of care for AHFS by providing at least some level of consensus and evidence-based treatment recommendations, the gap between the clinical evidence and actual practice is growing. Appropriate disease assessment, followed by the implementation of life-saving therapies, is the key to improving outcomes. Managed care initiatives, such as improved quality measures, disease management programs, patient education efforts, hospital discharge checklists, and pharmacy-led interventions to enhance medication compliance, provide potential solutions for combating the alarming rise of morbidity, mortality, and costs associated with this disease.