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

项目概述：结肠癌和直肠癌是癌症死亡的第二大原因， 美国，但通过早期发现浸润性或癌前病变可能可以预防。的 结肠镜检查是目前推荐的筛查平均风险人群的测试，是最常用的 在美国，但基于粪便的测试，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为这些决定提供重要的信息。 相互竞争的筛选策略，导致政策团体提出相互矛盾的建议， 加拿大工作组建议不要使用结肠镜检查进行常规筛查。微观模拟 研究报告称，FIT和结肠镜检查可以达到相似的总体寿命有效性，但基于 在真实的实践中无法实现的疗效和坚持定期筛查的假设。一个额外 挑战是缺乏完善的统计方法，可以解释不同程度的 依从性、使用模式（如交叉）和时间依赖性混杂， 结直肠癌（CRC）筛查试验的有效性。我们提出的一系列研究旨在：1）估计 与无筛查相比，FIT在降低CRC死亡风险方面的有效性，以及2） 比较FIT相对于筛查结肠镜检查在降低死于CRC风险方面的有效性。我们 还将根据人种/种族、性别和社会经济地位评估潜在效应改变。我们将使用一个 嵌套病例对照设计，在2014年至2018年的历史研究中约有2000例病例和8000例对照 大约200万符合筛查条件的人在Kaiser Permanente北方和南方接受护理 加州。本研究的病例将是死亡日期为52-89岁的男性和女性， CRC，每个健康计划内匹配的四个随机选择的控制基于年龄，性别，入组 历史和地理区域。作为次要的方法论目标，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 不完全依从性和从FIT到结肠镜检查的交叉; 2）评估病例队列设计的使用， 为今后的研究提供信息。作为一个探索性的目标，我们将描述用FIT或 结肠镜检查作为未来微观模拟研究的输入。我们的研究中心提供了癌症的完整连续性 从筛查到生命结束的护理，并提供有关CRC筛查的信息， 与大量人群的诊断和特定原因死亡率数据相联系。我们将确认收到 在参考日期前10年的窗口期内进行结肠镜检查和FIT筛查， 从诊断程序中筛选出选定的图表审核，以确认结肠镜检查筛选适应症。 这将是第一个解决这些关键的科学，临床和政策问题的观察性研究。的 该项目将由一个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.