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

个性化的癌症治疗正在成为现实。广泛基因组分析（BGP）的实际应用 已经能够同时测试数百种潜在的靶向基因改变， 癌专业协会已经认可BGP在几种癌症类型的临床实践中，包括 晚期非小细胞肺癌（aNSCLC）。然而，关于BGP对患者的影响的证据 随着靶向药物的可获得性、利用率和功效的变化，治疗结果也在不断变化。作为 因此，BGP的使用提出了癌症护理中的一个基本问题：利益相关者如何使最知情的 在存在不确定性的情况下做出决策？我们对信息价值（VOI）分析进行了验证， 量化了收集进一步证据的好处与基于以下因素的决策之间的权衡： 目前的证据，可用于指导有关BGP的决策。在本提案中，我们解决了 了解现实世界1）BGP的使用及其对2）临床决策的影响，3）治疗结果， 成本和4）额外的研究的价值，以经验为基础的决定，采用BGP到 通过利用多个互补的真实世界数据集的优势来治疗癌症。 目标1：BGP在当代美国癌症护理中的应用。我们将研究BGP在高级 癌症和患者体内检测的驱动因素（目标1A）Medicare 100%按服务收费和Medicare 优势和（目标1B）蓝十字蓝盾保险范围。 目的2：BGP结果及其对NSCLC治疗模式的影响。我们将量化 aNSCLC患者中的可操作突变（Aim 2A），并评估BGP与 癌症管理策略，因为只有不到一半的具有靶向突变的患者可以接受 相应的FDA批准的靶向治疗（Aim 2B）。 目标3：BGP成本和生存率。我们将确定BGP使用和癌症护理费用之间的关系 (Aim 3A）和总体和癌症特异性生存期（目标3B）。 目标4：成本效益和信息价值。我们将使用VOI分析来确定是否有额外的 需要证据/研究来支持BGP的使用。具体来说，我们将比较长期健康和 与aNSCLC患者中一线BGP相关的成本结局（目前推荐，但 有争议的）与两个替代战略，重点是较少数量的基因测试。我们将量化 证据中的关键差距，导致BGP有效性的不确定性， 对BGP进行额外研究，以改进关于BGP最佳实施的决策。 鉴于BGP的使用和有效性的不确定性，拟议的研究具有重要意义， 考虑到跨多个大型数据集的三角测量和VOI的合并， 鉴于晚期癌症的高负担和BGP的迅速使用，

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.