Effectiveness of screening for colorectal cancer in average risk adults: Colonoscopy vs FIT

项目摘要：结肠癌和直肠癌是我国癌症死亡的第二大原因。 但通过早期发现侵袭性或癌前病变可能是可以预防的。的 目前推荐用于筛查中等风险人群的检查，结肠镜检查是最常用的 在美国，但基于粪便的检测，如粪便免疫化学测试(FIT)，是最常见的 全球使用。然而，目前还没有强有力的证据来为这些具有重大影响的决定提供依据。 相互竞争的筛选策略，这导致政策小组提出相互矛盾的建议，包括 加拿大特别工作组建议不要将结肠镜检查用于常规筛查。微观模拟 研究报告称，FIT和结肠镜检查可以达到类似的总体终生效果，但基于 关于有效性和坚持定期筛查的假设在实际操作中是不可能实现的。添加了一条 挑战是缺乏完善的统计方法来解释不同水平的 依从性、交叉等使用模式，以及在估计 结直肠癌(CRC)筛查试验的有效性。我们提出的一系列研究的目的是：1)估计 与不筛查相比，FIT在降低死于结直肠癌风险方面的有效性，以及2) 比较FIT与筛查结肠镜在降低死于结直肠癌风险方面的有效性。我们 还将评估种族/民族、性别和社会经济地位的潜在影响修改。我们将使用 嵌套病例对照设计，2014-2018年间约2000例病例和8000例对照 约200万名符合筛查条件的患者在凯撒永久医院接受护理 加利福尼亚。这项研究的对象为男性和女性，他们在死于 CRC，每个在健康计划内与根据年龄、性别、登记人数随机选择的四个对照相匹配 历史和地理区域。作为第二个方法论目标，我们将：1)应用新的统计方法 评估FIT-结肠镜检查在不同现实生活筛查模式中的比较有效性，包括 从FIT到结肠镜检查的不完全坚持和交叉；以及2)评估病例队列设计的使用 通知未来的研究。作为一项探索性目标，我们将对筛选所需的资源进行描述 结肠镜检查作为未来微模拟研究的输入。我们的研究站点提供了完整的癌症连续体 从筛查到临终关怀，并提供有关结直肠癌筛查的信息， 与大量人口的诊断和特定原因死亡率数据相联系。我们将确认收据 筛查结肠镜检查和筛查符合在参考日期之前的10年窗口，区分 通过精选的图表审核从诊断程序中进行筛选，以确认结肠镜检查的适应症。 这将是解决这些关键的科学、临床和政策问题的第一项观察性研究。这个 该项目将由一支经验丰富的高影响力科学家团队实施。

PROJECT SUMMARY: Cancers of the colon and rectum are the second leading cause of cancer deaths in the United States, but are potentially preventable through early detection of invasive or precancerous lesions. Of the currently recommended tests for screening average risk people, colonoscopy is the most commonly used in the United States, but stool-based tests such as fecal immunochemical tests (FIT), are the most commonly used globally. However, there is currently no strong evidence to inform highly consequential decisions on these competing screening strategies, which contributes to conflicting recommendations from policy groups including a Canadian task force recommendation against using colonoscopy for routine screening. Microsimulation studies report that FIT and colonoscopy can achieve similar overall lifetime effectiveness, but are based on assumptions of efficacy and adherence to regular screening that are not attainable in real practice. An added challenge is the paucity of well-developed statistical approaches that can account for varying levels of adherence, patterns of use such as cross-overs, and time-dependent confounding when estimating the effectiveness of colorectal cancer (CRC) screening tests. Our proposed series of studies aim to: 1) estimate the effectiveness of FIT in reducing the risk of dying from CRC when compared with no screening, and 2) compare the effectiveness of FIT in reducing the risk of dying from CRC relative to screening colonoscopy. We will also assess for potential effect modification by race/ethnicity, sex, and socioeconomic status. We will use a nested case-control design with about 2000 cases and 8000 controls between 2014 and 2018 in a historical cohort of about 2 million screening-eligible people receiving care at Kaiser Permanente Northern and Southern California. Cases for the study will be men and women who were 52-89 years old at the date of death from CRC, each matched within health plan to four randomly selected controls based on age, sex, enrollment history, and geographic region. As secondary methodological aims, we will: 1) apply novel statistical methods to estimate FIT-colonoscopy comparative effectiveness in varying real-life screening patterns including imperfect adherence and crossover from FIT to colonoscopy; and 2) assess the use of a case-cohort design to inform future studies. As an exploratory aim, we will characterize the resources required to screen with FIT or colonoscopy as inputs for future microsimulation studies. Our study sites provide the full continuum of cancer care ranging from screening through end of life, and provide access to information on CRC screening that can be linked to diagnosis and cause-specific mortality data on large numbers of people. We will identify receipt of screening colonoscopy and screening FIT in the 10-year window prior to the reference date, differentiating screening from diagnostic procedures with selected chart audits to confirm colonoscopy screening indications. This will be the first observational study to address these critical scientific, clinical, and policy questions. The project will be implemented by an experienced team of high-impact scientists.