Making decisions using uncertain evidence: An exploration of health technology assessment (HTA) and subsequent decision-making processes for rare dise

在获得上市许可后，卫生技术，包括罕见病治疗（RDT），在不同的司法管辖区进行卫生技术评估（HTA），目的是在付款人关于技术覆盖和/或报销的决策中提供信息和建议。然而，由于疾病和治疗相关的挑战，RDT通常与有限和不确定的证据基础相关，这使得与其他替代品相比对其益处的判断变得复杂。此外，创新RDT的持续增长导致大量RDT报销申请，HTA系统需要及时响应。这给卫生技术评估人员提出了相当大的挑战，他们试图决定在公共资助的卫生系统内支付什么费用。他们将不得不平衡RDT的不确定证据，同时在有限资源的背景下努力满足庞大而多样化的罕见病患者人群的医疗保健需求。广泛的研究表明，卫生技术评估机构倾向于利用类似的方法来评估所提交的卫生技术证据，但各国的报销建议各不相同。此外，深入分析了卫生技术评估进程中RDT的挑战，以及通过定制方案解决RDT不确定性的方法，在定制方案中，往往接受不太可靠的证据。有时，研究探讨了不同国家的卫生技术评估机构如何考虑或评估不确定性。然而，研究，特别是集中在如何评估的不确定性，在卫生技术评估的RDTs是稀缺的。虽然卫生技术评估中的不确定性总是存在于某种程度上，但卫生技术评估机构如何考虑不确定性取决于具体情况和背景。因此，拟议中的研究旨在了解如何在英国和德国的卫生技术评估过程中解决这些困难和评估RDTs的不确定性，并探讨已被用来克服这些挑战的方法。定量方法将包括从卫生技术评估报告中提取的数据的统计分析，定性方法将包括从卫生技术评估机构，制药商和患者组织的关键线人访谈。我选择英国和德国作为分析的国家，因为这两个司法管辖区都有强大的制药行业，因此可以快速引入新的创新治疗方法。此外，卫生技术评估机构、卫生技术评估机构和卫生保健系统的类型在两个司法管辖区中的作用不同，但对于定价和报销目的同样重要。最后，这两个司法管辖区都将其卫生技术评估报告在网上公开，并且司法管辖区的语言不会对分析构成障碍。鉴于医疗保健部门的可用资源有限，这项研究有助于制定证据，为罕见疾病的资源分配决策提供信息。更好地了解RDTs的HTA中的不确定性可以提供重要的见解，以确保及时，负担得起和公平的患者获得创新治疗，更好地一致性决策RDTs，并改善罕见病患者的健康结果，最终有助于改善整体健康和福祉。应用定量和定性研究方法开发和执行协作，跨学科的研究设计开发卫生技术评估的专业知识，与研究用户建立联系，参与并建立网络，包括来自HTA机构，政策，学术界和罕见疾病患者组织的利益相关者提高可转移和领导技能

After having received marketing authorisation, health technologies, including rare disease treatments (RDTs), undergo health technology assessment (HTA) in different jurisdictions, with the purpose to inform and advise payers in their decision-making about coverage and/or reimbursement of the technology. However, due to disease- and treatment-related challenges, RDTs are typically associated with a limited and uncertain evidence base, which complicates judgements about their benefits in comparison to other alternatives. Additionally, the continuous growth in innovative RDTs is resulting in a high volume of RDT reimbursement applications to which HTA systems need to respond timely. This poses considerable challenges for HTA assessors seeking to make decisions about what to pay for within publicly funded health systems. They will have to balance the uncertain evidence for RDTs, while striving to meet the healthcare needs of a large and diverse rare disease patient population in the context of finite resources. Extensive research demonstrated that HTA bodies tend to draw on similar methodologies for evaluating the submitted evidence for health technologies, but reimbursement recommendations diverge across countries. Moreover, challenges of RDTs in HTA processes and approaches to addressing uncertainty around RDTs through bespoke programmes in which often less robust evidence is accepted have been analysed thoroughly. Occasionally, studies have explored how uncertainties are considered or assessed by HTA agencies in different countries. However, studies focusing particularly on how uncertainty is assessed in HTA for RDTs are scarce. While uncertainties are always present at some level in HTA, how uncertainty is considered by HTA agencies is situation- and context-specific. Therefore, the proposed research seeks to understand how HTA processes in England and Germany address these difficulties and evaluate uncertainty for RDTs, and explore approaches that have been used to overcome these challenges.Quantitative methods will include statistical analyses of extracted data from HTA reports, and qualitative methods will include interviews with key informants from HTA agencies, pharmaceutical manufacturers and patient organisations. I chose England and Germany as countries for analysis as both jurisdictions have a strong pharmaceutical industry presence and thus experience a rapid introduction of new and innovative treatments. In addition, the role of the HTA agencies, HTA practises, and the type of healthcare system are different in both jurisdictions but equally crucial for pricing and reimbursement purposes. Lastly, both jurisdictions make their HTA reports publicly available online and the languages of the jurisdictions for not pose a barrier for analysis.In light of limited available resources in the healthcare sector, this research contributes to the development of evidence that can inform resource allocation decisions for rare diseases. A better understanding about uncertainties in HTA for RDTs can provide important insights towards ensuring timely, affordable, and equitable patient access to innovative treatments, better consistency in decision-making for RDTs, and improve health outcomes of rare disease patients, ultimately contributing to better health and wellbeing overall.How the studentship meets ESRC skill priorities:Applying quantitative and qualitative research methodsDeveloping and executing a collaborative, interdisciplinary research designDeveloping specialized expertise in health technology assessment, and health economics and policyConnecting, engaging and establishing a network with research users, including stakeholders from HTA agencies, policy, academia, and rare disease patient organizationsImproving transferable and leadership skills