Maximizing yield of the fecal immunochemical test for colorectal cancer screening

描述(申请人提供)：结直肠癌(CRC)是美国癌症死亡的主要原因。结直肠癌筛查降低了结直肠癌死亡率，但美国的筛查率仍然很低。粪便潜血检测(FOBT)是唯一一种建立了效益和风险的积极平衡的结直肠癌筛查方法，是最便宜的，也是近一半患者的首选方法。一种较新的粪便筛查测试，粪便免疫化学测试(FIT)，比FOBT有了显著的改进。与FOBT相比，它更易于使用，在检测结直肠癌和癌前病变方面也更敏感。OC-Micro FIT特别令人感兴趣，因为它具有高度的敏感性和特异性，是美国批准的唯一可以自动处理的FIT测试。因此，OC-Micro是用于大规模筛查项目以提高社区结直肠癌筛查率的最佳方法。然而，OC-Micro之前的研究受到几个限制：它们是在不适合评估美国平均风险患者的筛查性能的人群中进行的，并且研究没有明确确定所需的最佳样本数量和检测阳性的切入点。因此，MY-FIT(最大化粪便免疫化学检测的产量)研究的总体目标是利用研究地点高度集成和广泛的电子病历系统来收集两组独立的数据，当合成后，将提供使用OC-Micro Fit的不同方案的比较患者依从性、敏感性、特异性和成本的详细情况。具体地说，在50-75岁的KPNW成员中，他们是结直肠癌(CRC)的平均风险人群(n=78,000)，我们建议：1.使用不同的阳性测试切入点(n=2100)，比较单样本匹配(1-Fit)和两样本匹配(2-Fit)对结直肠癌和晚期腺瘤(晚期肿瘤)的敏感性、特异性、阳性预测值和阴性预测值。2.比较患者完成1-Fit和2-Fit方案的依从性(n=3000)。3.评估和比较1-Fit和2-Fit方案的每个筛查成本，以及在1-Fit和2-Fit方案中发现的晚期肿瘤的成本(使用不同的阳性测试切点)(n=78,000)。回答上述问题将为在美国普通人群中使用OC-Micro Fit筛查CRC的最佳实践、成本效益高的方法提供急需的强有力的证据基础。 公共卫生相关性：结直肠癌(CRC)是美国癌症死亡的第二大原因，对男性和女性的影响几乎相等。结直肠癌的筛查减少了这种癌症的死亡率，但美国的筛查率仍然很低。该项目旨在提供证据，指导使用一种较新的筛查试验，即粪便免疫化学试验(FIT)，以取代最广泛使用的粪便检测，FOBT。FITS比目前的粪便检测方法更容易使用，更准确，更便宜，是在普通人群中使用的理想方法。然而，这些测试还没有在大量人群中进行过试验。我们的项目将回答有关使用这种改进的结肠癌检测方法的最佳、最准确的方法的问题。

DESCRIPTION (provided by applicant): Colorectal cancer (CRC) is a leading cause of cancer death in the United States. Screening for CRC reduces CRC mortality, yet rates of screening in the United States remain low. Fecal occult blood testing (FOBT) is the only CRC screening method with an established positive balance of benefit and risk, is the least expensive, and is the preferred method for nearly half of patients. A newer fecal screening test, the fecal immunochemical test (FIT), offers significant improvements over the FOBT. It is easier to use and is more sensitive at detecting both CRC and precancerous adenomas than the FOBT. The OC-Micro FIT is of particular interest because it is highly sensitive and specific and it is the only FIT test approved in the US that can be processed in an automated manner. Thus, the OC-Micro is an optimal method for use in mass screening programs to improve community CRC-screening rates. However, prior studies of OC-Micro suffer from several limitations: they were conducted in populations not optimal for assessing screening performance in average risk patients in the U.S. and the studies did not clearly establish optimal number of samples required and cut-points for test positivity. Therefore, the overall goal of the MY-FIT (Maximizing the Yield of Fecal Immunochemical Tests) study is to capitalize on the highly integrated and extensive electronic medical record system of the study site to collect two separate sets of data that, when synthesized, will provide a thorough picture of the comparative patient adherence to, sensitivity, specificity, and costs of different protocols for using the OC-Micro FIT. Specifically, among KPNW members aged 50-75 who are at average risk for colorectal cancer (CRC) and who are due for CRC screening (n=78,000), we propose to: 1. Compare the sensitivity, specificity, positive predictive value, and negative predictive value for colorectal cancer and advanced adenoma (advanced neoplasia) between a single-sample FIT (1-FIT) and a two- sample FIT (2-FIT) using varying cut points for a positive test (n=2100). 2. Compare patient adherence to completion of a 1-FIT versus a 2-FIT protocol (n=3000). 3. Assess and compare cost per screen for a 1-FIT versus a 2-FIT protocol, and the cost per advanced neoplasia detected in a 1-FIT versus a 2-FIT protocol (using varying cut points for a positive test) (n=78,000). Answering the above questions will provide a much-needed strong evidence base for a best-practice, cost- effective method of using the OC-Micro FIT to screen for CRC in a general U.S. population. PUBLIC HEALTH RELEVANCE: Colorectal cancer (CRC) is the second leading cause of cancer death in the United States, and affects men and women almost equally. Screening for CRC reduces deaths from this cancer, yet rates of screening in the United States remain low. This project aims to provide evidence to guide use of a newer screening test, the fecal immunochemical test (FIT), to replace the most widely used fecal test, the FOBT. FITs are easier to use, more accurate, and cheaper than current methods of fecal testing, and are ideal for use in the general population. However, these tests have not been tried in large populations. Our project will answer questions about the best, most accurate way to use this improved test for colon cancer.