Assessing the generalisability of heart failure medication trials in a real-world population – a large-scale registry-based analysis in the Swedish heart failure registry (SwedeHF)

评估现实世界人群心力衰竭药物试验的普遍性——瑞典心力衰竭登记处 (SwedeHF) 的大规模登记分析

• 批准号: 535014557
• 负责人: Dr. Benedikt Beer
• 金额: --
• 依托单位: Karolinska Institutet
• 依托单位国家: 德国
• 项目类别: WBP Fellowship
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/535014557?language=en
• 关键词: Assessing; generalisability; heart; failure; medication

Heart failure is a global pandemic with a 1-year mortality of approximately 36%. The prevalence in Germany, Italy and Sweden is roughly 2% - and rising in an ageing population. A better understanding of heart failure’s pathophysiology has paved the way for prognosis improving medical drugs like beta blockers, renin-angiotensin system inhibitors, mineralocorticoid receptor antagonists, SGLT2 inhibitors as well as by Vericiguat in selected patients and potentially Omecamtiv mecabil in the future. Randomised controlled trials are today’s gold standard for the assessment of such therapeutical interventions. They are able to describe causal relationships between an intervention and a defined outcome and are therefore the foundation of evidence-based medicine. There are two main quality indicators of trial quality: internal and external validity. Internal validity captures the trial’s capability to rule out other than the intervention’s influence on the outcome. It is impaired by both systematic and random errors. These challenges can be encountered by, e.g., a proper sample size. Increasing the sample size, on the other hand, results in considerable increase of the trial’s expenditure, longer duration of study participant recruitment and exposure of more participants to potential safety issues. Thus, enrichment strategies have been developed by study sponsors and endorsed by regulative authority bodies. However, these strategies may come at the cost of external validity. External validity describes the extent to which a trial’s results can be applied to the target population and can thus be generalised in clinical practice. The aspect of external validity has not been in the scope of clinical research until recently. As a consequence, only current trials have been investigated with a focus on the generalisability of their results to the target population, yet. Therefore, it is of interest to (re-) assess older trials which are still relevant for nowadays guideline recommendations on heart failure medication about their generalisability to a real-world heart failure population. The applicant plans to do so employing the unique Swedish Heart Failure Registry (SwedeHF): SwedeHF is designed as a nationwide continuous health quality and research registry; it was founded in 2000 and until 2003 implemented in the whole of Sweden. Vastly more than 100,000 registrations and 60,000 patients have been included added by approximately 10,000 further registrations of both known and new patients each year. In this project, the applicant aims to: (1) gain insight into registry-based heart failure research, (2) analyse the generalisability of past HFrEF trials, (3) propose a pragmatic trial design in heart failure research between the poles of internal and external validity and (4) learn fundamentals in registry-based randomised trials and assessing their potential for future evidence-based medicine in heart failure.

心力衰竭是一种全球性的流行病，1年死亡率约为36%。德国、意大利和瑞典的患病率约为2%，随着人口老龄化，这一比例还在上升。对心力衰竭病理生理学的更好了解为改善预后的药物铺平了道路，如β受体阻滞剂、肾素-血管紧张素系统抑制剂、盐皮质激素受体拮抗剂、SGLT2抑制剂以及Vericiguat在选定患者中的应用，以及未来可能使用的Omecamtiv Mecabil。随机对照试验是当今评估此类治疗干预措施的黄金标准。它们能够描述干预措施和确定的结果之间的因果关系，因此是循证医学的基础。审判质量主要有两个质量指标：内部效度和外部效度。内部有效性体现了试验排除干预对结果的影响以外的其他因素的能力。它受到系统误差和随机误差的影响。这些挑战可以通过例如适当的样本量来遇到。另一方面，增加样本量会导致试验支出大幅增加，招募研究参与者的时间更长，并使更多参与者暴露在潜在的安全问题中。因此，研究赞助者制定了浓缩战略，并得到监管机构的认可。然而，这些策略可能是以外部有效性为代价的。外部有效性描述了试验结果可以在多大程度上应用于目标人群，从而可以在临床实践中推广。外部效度直到最近才进入临床研究的范围。因此，目前只对目前的试验进行了调查，重点是其结果对目标人群的普适性。因此，(重新)评估旧的试验是有意义的，这些试验仍然与当今关于心力衰竭药物的指南建议有关，即它们对现实世界心力衰竭人群的普适性。申请者计划使用独特的瑞典心力衰竭登记处(SwedeHF)：瑞典心力衰竭登记处是一个全国性的持续健康质量和研究登记处；它成立于2000年，直到2003年在整个瑞典实施。超过100,000个注册和60,000名患者被包括在内，每年新增约10,000个已知和新患者的注册。在这个项目中，申请者的目标是：(1)深入了解基于登记的心力衰竭研究，(2)分析过去HFrEF试验的概括性，(3)在心力衰竭研究中提出介于内部和外部有效性两极之间的务实试验设计，以及(4)在基于登记的随机试验中学习基础知识，并评估其在未来心力衰竭循证医学中的潜力。