Modeling the Disease Burden and Cost-Effectiveness of Screening and Treatment for Non-Alcoholic Fatty Liver Disease in Type 2 Diabetes Patients

模拟 2 型糖尿病患者非酒精性脂肪肝筛查和治疗的疾病负担和成本效益

• 批准号: 10474392
• 负责人: Srinivasan Dasarathy
• 金额: $ 38.92万
• 依托单位: CLEVELAND CLINIC FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10474392
• 关键词: Modeling; Disease; Burden; Cost; Effectiveness

Project Summary/Abstract In the US, type 2 diabetes (T2D) is a major cause of morbidity and mortality due to microvascular and macrovascular complications. Nonalcoholic fatty liver disease (NAFLD) is another common co-morbidity but its burden in patients with T2D is poorly studied. Although NAFLD affects 50-70% of T2D patients, there is neither a screening guideline nor established treatment for NAFLD. Besides weight loss, pioglitazone – an old diabetes drug – is the only drug recommended by the American Association for the Study of Liver Diseases for treating NASH, the more progressive form of NAFLD, in patients with T2D. In addition, liraglutide (in phase 2 trials) and obeticholic acid (with phase 3 interim data) appear effective for improving NASH and advanced fibrosis. At least 4 other drugs (making a total of 5) are undergoing phase 3 trials and up to 50 drugs are in phase 2 trials. As new drugs become available in the near future, physicians and patients will face difficult tradeoffs among long-term benefits, risks, and costs. Given the widespread nature of NAFLD in patients with T2D, screening to identify those with NASH, who are at high-risk of advance liver disease, for early intervention may help patients live longer with a better quality life. Yet, the lack of comparative effectiveness and cost- effectiveness analyses of screening for NAFLD has resulted in conflicting clinical guidelines. Choosing the best treatment and screening strategy for NAFLD is complicated and can be aided by the use of computer-based models. Unfortunately, existing diabetes models do not include NAFLD, and NAFLD models do not account for diabetes and its complications. The objective of this study is to develop a computer simulation model of NAFLD in T2D to estimate its burden, and evaluate treatment and screening options for NASH. Specific aims are: 1) Develop and validate a microsimulation model of the natural history of NAFLD, including NASH; 2) Estimate and project the burden of NAFLD-associated liver complications in patients with T2D until 2030; 3) Assess the cost-effectiveness of treatments for NASH in patients with T2D; and 4) Evaluate the cost-effectiveness of screening for NASH in patients with T2D. This proposal builds upon our inter-disciplinary team’s strong foundation of constructing decision models to assist clinical decision making and studying the epidemiology of diabetes and NAFLD. Our model will provide a better understanding of a prevalent, important, yet underappreciated diabetes complication, using an innovative approach to diabetes and liver disease modeling. The study also establishes the groundwork for future evaluation of new treatment regimens and screening modalities for patients with T2D and NAFLD, which will advance the prevention and treatment of both diseases for millions of patients each year.

项目概要/摘要 在美国，2 型糖尿病 (T2D) 是由于微血管和糖尿病引起的发病和死亡的主要原因。 大血管并发症。非酒精性脂肪肝 (NAFLD) 是另一种常见的合并症，但其 T2D 患者的负担研究很少。尽管 NAFLD 影响 50-70% 的 T2D 患者，但 NAFLD 的筛查指南或既定治疗方法。除了减肥，吡格列酮——一种老药 糖尿病药物——是美国肝病研究协会推荐的唯一药物 治疗 T2D 患者的 NASH（NAFLD 的更进展形式）。此外，利拉鲁肽（2期 试验）和奥贝胆酸（具有 3 期中期数据）似乎可有效改善 NASH 和晚期 纤维化。至少有 4 种其他药物（总共 5 种）正在进行 3 期试验，多达 50 种药物正在研究中 第二阶段试验。随着新药的出现，医生和患者将面临困难 长期利益、风险和成本之间的权衡。鉴于 NAFLD 在患者中的广泛性 T2D，筛查以确定患有晚期肝病高风险的 NASH 患者，以便进行早期干预 可以帮助患者延长寿命并提高生活质量。然而，缺乏比较有效性和成本 NAFLD 筛查的有效性分析导致了相互矛盾的临床指南。选择最好的 NAFLD 的治疗和筛查策略很复杂，可以通过使用基于计算机的 模型。不幸的是，现有的糖尿病模型不包括 NAFLD，而 NAFLD 模型也没有考虑到 NAFLD。 糖尿病及其并发症。本研究的目的是开发 NAFLD 的计算机模拟模型 评估 T2D 的负担，并评估 NASH 的治疗和筛查方案。具体目标是：1） 开发并验证 NAFLD（包括 NASH）自然史的微观模拟模型； 2) 预估 并预测到 2030 年 T2D 患者与 NAFLD 相关的肝脏并发症的负担； 3）评估 T2D 患者 NASH 治疗的成本效益； 4) 评估成本效益 T2D 患者 NASH 筛查。该提案建立在我们跨学科团队强大的基础上 构建辅助临床决策的决策模型和研究流行病学的基础 糖尿病和 NAFLD。我们的模型将更好地理解流行的、重要的但 使用创新的糖尿病和肝病建模方法来解决被低估的糖尿病并发症。 该研究还为未来评估新治疗方案和筛查奠定了基础 针对 T2D 和 NAFLD 患者的治疗方法，这将促进这两种疾病的预防和治疗 每年为数百万患者服务。