Cost-Effectiveness Analysis of Age-and Gender-Based Colorectal Cancer Screening

描述（由申请人提供）：在了解晚期腺瘤的患病率如何导致结直肠癌的发病率和死亡率以及这种因果关系如何在年龄和性别上存在差异方面存在巨大差距。这一差距的持续存在是一个重要的问题，因为直到它被填补，选择更好的结直肠癌筛查策略，以不同的人群亚组，其特征在于年龄类别和性别，导致成本效益高的以患者为中心的结直肠癌筛查将仍然在很大程度上无法实现。长期目标是确定CRC筛查是否可以主要根据预测的晚期腺瘤患病率为个体患者定制，这些患者不存在其他CRC风险。在这个特定的应用程序的目的是预测，通过离散事件微观模拟，CRC的发病率，死亡率和成本效益的应用推荐的筛查策略，以不同的年龄-性别亚组。最近在一些临床观察性研究中显示了年龄和性别的CRC风险差异。然而，它们还没有被任何指南组织纳入筛查指南的制定中。核心假设是，根据年龄和性别定制的筛查建议比非定制策略更有效和更具成本效益。这一假设是基于最近几项描述晚期腺瘤的年龄和性别特异性患病率的研究，包括我们的初步研究。这项研究的基本原理是，通过将筛查结肠镜临床数据纳入CRC自然史模型，并比较代表性筛查策略的增量成本效益比，我们可以提出令人信服的基于年龄和性别的政策建议。在我们团队每个成员的良好记录和我们过去成功合作的保证下，这一假设将通过追求两个具体目标进行测试：1）估计CRC自然史的年龄和性别特异性参数，例如，腺瘤的发病率和进展率; 2）评价年龄和性别为基础的人群亚组的代表性筛查策略的比较有效性和成本效益。在第一个目标下，模拟年龄和性别依赖性CRC自然史的离散事件模拟模型将用我们可用的筛选结肠镜观察数据进行校准。在第二个目标下，将使用定制的模拟来估计相对成本、风险和收益， 在第一个目标下获得，在不同年龄-性别亚组的代表性筛查策略中。该研究方法具有创新性，因为它应用离散事件模拟来进行更复杂的CRC自然史建模和更详细的筛查策略建模。拟议的研究是重要的，因为它将提供所需的知识，导致个性化的CRC筛查。最终，这些知识有可能为以患者为中心的CRC筛查的指南制定提供信息，这将有助于提供更有效和更具成本效益的CRC预防和控制。

DESCRIPTION (provided by applicant): There is a substantial gap in understanding how prevalence of advanced adenomas leads to incidence and mortality of colorectal cancer and how such causality differs in age and gender. Continued existence of this gap represents an important problem because until it is filled, selection of preferable colorectal cancer screening strategies for distinct population subgroups characterized by age category and gender that lead to cost-effective patient-centered colorectal cancer screening will remain largely unachievable. The long-term goal is to determine whether CRC screening may be tailored based primarily on the predicted prevalence of advanced adenomas for individual patients who do not present other CRC risks. The objective in this particular application is to predict, via discrete-event microsimulation, CRC incidence, mortality, and cost-effectiveness of applying recommended screening strategies to distinct age-gender subgroups. The differences in CRC risk by age and gender have recently been shown in a number of clinical observational studies. However, they have not been incorporated in screening guideline development by any guideline organization. The central hypothesis is that screening recommendations tailored by age and gender are more effective and cost- effective than non-tailored strategies. This hypothesis has been formulated on the basis of several recent studies describing age- and gender-specific prevalence of advanced adenomas, including our preliminary study. The rationale for the proposed research is that by incorporating screening colonoscopy clinical data into CRC natural history modeling and comparing incremental cost-effectiveness ratios among representative screening strategies, we can make convincing age- and gender-based policy recommendations. Ensured by the strong track record of each member on our team and our successful collaborations in the past, this hypothesis will be tested by pursuing two specific aims: 1) Estimate the age- and gender-specific parameters of the natural history of CRC, e.g., adenoma incidence and progression rates; and 2) Evaluate the comparative effectiveness and cost-effectiveness of representative screening strategies for age- and gender-based population subgroups. Under the first aim, a discrete-event simulation model that mimics the age- and gender- dependent CRC natural history will be calibrated with screening colonoscopy observational data available to us. Under the second aim, relative costs, risks, and benefits will be estimated with the tailored simulation, obtained under the first aim, among representative screening strategies for distinct age-gender subgroups. The approach in the proposed research is innovative, because it applies discrete-event simulation to conduct more complex modeling of CRC natural history and more detailed modeling of screening strategies. The proposed research is significant, because it will provide the knowledge required to lead to individualization of CRC screening. Ultimately, such knowledge has the potential to inform the guideline development of patient- centered CRC screening that will help to delivery more efficient and cost-effective CRC prevention and control.