A preliminary application of a haemophilia value framework to emerging therapies in haemophilia.

INTRODUCTION: Emergence of new therapies are anticipated to improve clinical outcomes and quality of life of persons with haemophilia. Challenges in conducting randomized clinical trials in rare diseases have resulted in a lack of direct head-to-head comparisons to support value-based decision-making between different treatments. METHODS: We conducted a literature review for new and emerging haemophilia A and B therapies (extended half-life [EHL] replacement factor, non-replacement therapies [NRT], and gene therapies [GT]) to identify differentiating patient-centred outcomes defined previously in a haemophilia value framework. Since the literature included all publication types (e.g., surveys, modelling studies, commentaries/reviews), collected data were assigned level of evidence scores. RESULTS: Across different classes of therapies, bleeding was determined as the most frequently reported differentiating outcome, with EHL, NRT, and GT each demonstrating an advantage over comparator replacement therapies. EHL therapies for haemophilia A and B and NRT for haemophilia A showed good representation across Tier 1 outcomes (health status achieved/retained), while more publications were identified with Tier 2 (process of recovery) outcomes for NRT than EHL or GT. In Tier 3 (sustainability of health), frequency of breakthrough bleeds represented a differentiating outcome for EHL (both haemophilia A and B), NRT (haemophilia A only), and GT (haemophilia B only), whereas sustained good health was differentiating for most comparisons. CONCLUSIONS: We demonstrate the utility of the haemophilia value framework as a common core outcome set for effectively comparing therapies. Application of this framework will serve as a useful decision-making tool for patients, clinicians, and within health technology assessments. KEY POINTS OF CONSIDERATION: With the emergence of high-cost, paradigm changing treatments across multiple areas of medicine, we, the haemophilia community, need to be equipped to meet the growing demands for more rigorous evidence-based value assessments using the tools expected by assessors. The traditional access toolbox needs to evolve to meet the paradigm shift in treatment options. Value can no longer be defined by annualized bleed rates alone. To realize the full impact of new therapies, we need to utilize tools, such as a value framework, to organize evidence, identify data gaps, and assess patient-defined, meaningful outcomes across a multi-faceted dimension. The haemophilia value framework is an effective tool for organizing the available evidence and identifying gaps in the evidence. This can be used for assessing the value of emerging therapies in haemophilia utilizing data generated through randomized clinical trials and real world evidence generation. This is a call for incorporating the Value Framework into official submissions to authorities, as it captures a broader range of outcomes, including patient meaningful outcomes, in ways that better assess the potential benefits of new therapies.

Preparing for tomorrow: Defining a future agenda.

Gene therapy will be the first long-term therapy with potential to produce a functional cure for haemophilia. As a single dose ('once-and-done') therapy with significant uncertainties regarding impact and duration of factor expression, flexibility and adaptability of (1) value framework, (2) health technology assessment (HTA) methodology, and (3) development of alternative payment models will be needed for adoption of this new technology and to facilitate transparent decision-making to support its implementation. The responsibility for each of these currently lies with distinct entities, underscoring a need for enhanced collaboration between all stakeholders, as expanded engagement by key stakeholders will be critical to optimizing the assessment of value, enabling an optimised approach to HTA, and opening receptivity to new and innovative payment models. This supplement issue describes important considerations for a gene therapy 'toolkit', highlighting key considerations for each of the aforementioned tools, which will be useful for guiding decision-making regarding gene therapy as a novel treatment modality. In this article, we outline how the tools presented in this supplement can be applied as part of a framework to address the requirements of the relevant stakeholders, including payers, manufacturers, treaters, and patients. The paper also provides an illustrative example of how to understand the features of alternative payment models depending on the organization of and payment for healthcare.

Internal medicine resident knowledge of transfusion medicine: results from the BEST-TEST international education needs assessment.

BACKGROUND: Blood transfusion is the most common hospital procedure performed in the United States. While inadequate physician transfusion medicine knowledge may lead to inappropriate practice, such an educational deficit has not been investigated on an international scale using a validated assessment tool. Identifying specific deficiencies is critical for developing curricula to improve patient care. STUDY DESIGN AND METHODS: Rasch analysis, a method used in high-stakes testing, was used to validate an assessment tool consisting of a 23-question survey and a 20-question examination. The assessment tool was administered to internal medicine residents to determine prior training, attitudes, perceived ability, and actual knowledge related to transfusion medicine. RESULTS: A total of 474 residents at 23 programs in nine countries completed the examination. The overall mean score of correct responses was 45.7% (site range, 32%-56%). The mean score for Postgraduate Year (PGY)1 (43.9%) was significantly lower than for PGY3 (47.1%) and PGY4 (50.6%) residents. Although 89% of residents had participated in obtaining informed consent from a patient for transfusion, residents scored poorly (<25% correct) on questions related to transfusion reactions. The majority of residents (65%) would find additional transfusion medicine training "very" or "extremely" helpful. CONCLUSION: Internationally, internal medicine residents have poor transfusion medicine knowledge and would welcome additional training. The especially limited knowledge of transfusion reactions suggests an initial area for focused training. This study not only represents the largest international assessment of transfusion medicine knowledge, but also serves as a model for rigorous, collaborative research in medical education.