Broad Genomic Profiling in patients with advanced lung cancer: empirically assessing adoption, clinical utility, and the value of additional evidence in an evolving landscape of cancer care

晚期肺癌患者的广泛基因组分析：实证评估采用、临床效用以及在不断发展的癌症治疗领域中额外证据的价值

• 批准号: 10800129
• 负责人: Michaela Ann Dinan
• 金额: $ 70.67万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-20 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10800129
• 关键词: Address; Adoption; Advanced Malignant Neoplasm; Age; Blue Cross; Blue Shield; Clinical; Clinical effectiveness; Continuity of Patient Care; Data Set; Decision Making; Decision Modeling; Diagnosis; Effectiveness; Epidermal Growth Factor Receptor; FDA approved; Fee-for-Service Plans; Frequencies; Genomics; Geography; Health; Histology; Insurance; Insurance Coverage; KRAS2 gene; Label; Malignant Neoplasms; Malignant neoplasm of lung; Medicare; Modeling; Mutation; Neighborhoods; Non-Small-Cell Lung Carcinoma; Oncology; Outcome; Patient-Focused Outcomes; Patients; Policies; Policy Maker; Population Study; Prevalence; Professional Organizations; Recommendation; Research; Research Personnel; Smoking Status; Socioeconomic Status; Solid Neoplasm; Testing; Time; Treatment Cost; Treatment outcome; Uncertainty; actionable mutation; cancer care; cancer therapy; cancer type; care costs; clinical decision-making; clinical practice; clinically relevant; comorbidity; cost; cost effective; cost effectiveness; cost outcomes; frailty; genetic testing; improved; innovation; large datasets; patient population; personalized cancer therapy; research study; targeted agent; targeted treatment; timeline; treatment pattern

Personalized cancer treatment is becoming a reality. The real-world adoption of broad genomic profiling (BGP) has enabled the simultaneous testing of hundreds of potentially targetable genetic alterations in patients with cancer. Professional societies have endorsed BGP in clinical practice for several cancer types, including advanced stage non-small cell lung cancer (aNSCLC). Yet evidence regarding the impact of BGP on patient outcomes is constantly evolving, with changes in the availability, utilization, and efficacy of targeted agents. As such, BGP use raises a fundamental question in cancer care: how can stakeholders make the most informed decisions in the presence of uncertainty? We posit that Value of Information (VOI) analysis, which explicitly quantifies the trade-off between the benefits of collecting further evidence compared to a decision based on current evidence, can be used to guide decisions regarding BGP. In this proposal, we address the critical need to understand real-world 1) BGP use and its impact on 2) clinical decision-making, 3) treatment outcomes and costs and 4) the value of additional research to empirically inform decisions about the adoption of BGP into cancer care by leveraging the strengths of multiple complementary, real-world datasets. Aim 1: Utilization of BGP across contemporary U.S. cancer care. We will examine BGP use in advanced cancer and drivers of testing within patients with (Aim 1A) Medicare 100% Fee-for-Service and Medicare Advantage and (Aim 1B) Blue Cross Blue Shield insurance coverage. Aim 2: BGP results and their impact on treatment patterns in NSCLC. We will quantify the frequency of actionable mutations among patients with aNSCLC (Aim 2A) and assess the relationship between BGP and cancer management strategy, given that less than half of patients with a targetable mutation may receive the corresponding FDA-approved targeted therapy (Aim 2B). Aim 3: BGP cost and survival. We will determine the relationship between BGP use and cancer care costs (Aim 3A) and overall and cancer-specific survival (Aim 3B). Aim 4: Cost Effectiveness & Value of Information. We will use VOI analysis to determine whether additional evidence/research is needed to support the use of BGP. Specifically, we will compare the long-term health and cost outcomes associated with 1st line BGP in patients with aNSCLC (currently recommended but controversial) with two alternate strategies that focus on a smaller number of genetic tests. We will quantify critical gaps in the evidence that drive uncertainty regarding effectiveness of BGP and quantify the value of conducting additional research on BGP in order to improve decisions about optimal implementation of BGP. The proposed research is significant given uncertainty regarding the use and effectiveness of BGP, innovative given the triangulation across multiple large datasets and incorporation of VOI to guide practice and inform policy, and clinically relevant given the high burden of advanced cancer and the burgeoning use of BGP.

个性化的癌症治疗已成为现实。现实的采用广泛的基因组分析（BGP） 已经实现了数百种潜在靶向遗传改变患者的同时测试 癌症。专业社会已认可了几种癌症类型的临床实践中的BGP，包括 晚期非小细胞肺癌（ANSCLC）。但是有关BGP对患者的影响的证据 结果正在不断发展，随着目标剂的可用性，利用率和功效的变化。作为 这样的BGP使用提出了癌症护理中的基本问题：利益相关者如何使知情 在不确定性面前的决定？我们认为信息的价值（VOI）分析明确 量化收集进一步证据的收益与基于决定的决策之间的权衡 当前的证据可用于指导有关BGP的决策。在此提案中，我们满足了关键需求 了解现实世界1）BGP使用及其对2）临床决策的影响，3）治疗结果和 成本和4）额外研究的价值，以实证为关于BGP采用的决定 通过利用多个互补的现实世界数据集的优势来护理癌症护理。 目标1：在当代美国癌症护理中使用BGP。我们将检查高级BGP的使用 （AIM 1A）Medicare患者中的癌症和测试驱动因素100％支付费用和Medicare 优势和（AIM 1B）蓝十字蓝盾保险范围。 AIM 2：BGP结果及其对NSCLC治疗模式的影响。我们将量化 ANSCLC患者（AIM 2A）的可行突变，并评估BGP和BGP之间的关系 鉴于癌症管理策略不到一半，可靶向突变的患者可能会接受 相应的FDA批准的靶向治疗（AIM 2B）。 目标3：BGP成本和生存。我们将确定BGP使用与癌症护理成本之间的关系 （AIM 3A）以及整体和癌症特异性生存期（AIM 3B）。 目标4：成本效益和信息价值。我们将使用VOI分析来确定是否其他 需要证据/研究来支持BGP的使用。具体而言，我们将比较长期健康和 ANSCLC患者的第一行BGP相关的成本成果（目前建议但 有争议的）具有两种替代策略，重点是较少的基因检测。我们将量化 在证据中，临界差距是推动BGP有效性的不确定性并量化的价值 对BGP进行其他研究，以改善有关BGP最佳实施的决策。 鉴于BGP的使用和有效性不确定性，拟议的研究非常重要 考虑到多个大型数据集的三角剖分以及VOI的合并以指导实践并告知 鉴于晚期癌症的高负担以及BGP的迅速使用，政策以及临床相关。