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

描述(由申请人提供)：在了解晚期腺瘤的流行如何导致结直肠癌的发病率和死亡率以及这种因果关系在年龄和性别上如何不同方面存在很大差距。这一差距的持续存在是一个重要的问题，因为在填补这一差距之前，为以年龄类别和性别为特征的不同人口亚组选择更好的结直肠癌筛查策略，从而导致以患者为中心的成本效益高的结直肠癌筛查在很大程度上仍是不可能实现的。长期目标是确定是否可以主要根据预测的晚期腺瘤患病率对不存在其他结直肠癌风险的个体患者进行结直肠癌筛查。这一特殊应用的目的是通过离散事件微模拟预测CRC发病率、死亡率和将推荐的筛查策略应用于不同的年龄-性别亚组的成本效益。最近，一些临床观察性研究表明，不同年龄和性别的结直肠癌风险存在差异。然而，它们还没有被任何指南组织纳入筛选指南的制定中。中心假设是，根据年龄和性别量身定做的筛查建议比非量身定制的策略更有效、更具成本效益。这一假说是基于最近几项描述晚期腺瘤的年龄和性别患病率的研究提出的，包括我们的初步研究。拟议研究的基本原理是，通过将筛查结肠镜检查临床数据纳入结直肠癌自然历史模型，并比较代表性筛查策略中的增量成本-效果比，我们可以做出令人信服的基于年龄和性别的政策建议。我们团队中每个成员的良好记录和我们过去的成功合作确保了这一假设，将通过追求两个具体目标来检验这一假设：1)估计结直肠癌自然历史的年龄和性别特定参数，例如腺瘤发生率和进展率；2)评估具有代表性的筛查策略对年龄和性别人口亚组的比较有效性和成本效益。在第一个目标下，一个模拟年龄和性别相关的结直肠癌自然历史的离散事件模拟模型将利用我们可用的结肠镜检查观察数据进行校准。在第二个目标下，将通过量身定制的模拟来估计相对成本、风险和收益， 根据第一个目标，在针对不同年龄-性别分组的代表性筛查战略中获得。所提出的研究方法具有创新性，因为它应用离散事件仿真对CRC自然历史进行了更复杂的建模，并对筛选策略进行了更详细的建模。这项拟议的研究意义重大，因为它将提供导致结直肠癌筛查个体化所需的知识。最终，这些知识有可能为以患者为中心的结直肠癌筛查指南的制定提供信息，这将有助于提供更有效和更具成本效益的结直肠癌预防和控制。

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.