Point of care, real-time urine metabolomics test to diagnose colorectal cancers and polyps in low- and middle-income countries

护理点实时尿液代谢组学测试可诊断低收入和中等收入国家的结直肠癌和息肉

• 批准号: 10173098
• 负责人: OLUSEGUN ISAAC ALATISE
• 金额: $ 76.7万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-15 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10173098
• 关键词: Advanced Malignant Neoplasm; Advisory Committees; Age-Years; Alberta province; Bedside Testings; Belief; Benign; Biological Assay; Biosensor; Businesses; Canada; Cancer Control; Cancer Diagnostics; Clinical Trials; Clinics and Hospitals; Colonoscopy; Colorectal Cancer; Colorectal Polyp; Cost Effectiveness Analysis; Country; DNA; Data; Databases; Death Rate; Development; Device or Instrument Development; Devices; Diagnosis; Diagnostic tests; Disease; Endoscopy; Engineering; Ensure; Excision; Exposure to; Family history of; Feces; Goals; Grant; Guidelines; Health Priorities; Health system; Hemorrhage; Hospitals; Incidence; Income; Industry; Malignant Neoplasms; Marketing; Measures; Medical Device; Medical center; Medicine; Microfluidic Microchips; Modality; Morbidity - disease rate; Nigeria; Nigerian; Nuclear Magnetic Resonance; Outcome; Patient-Focused Outcomes; Patients; Phase; Physicians; Polyps; Population; Precancerous Polyp; Price; Prospective Studies; Public Health; Recording of previous events; Research; Research Personnel; Risk; Risk Factors; Scientist; Ships; Specificity; Specimen; Teaching Hospitals; Technology; Testing; Time; United Nations; United States National Institutes of Health; Universities; Update; Urine; Validation; World Health Organization; advanced disease; base; biobank; cancer care; cancer diagnosis; college; colon cancer patients; colorectal cancer prevention; colorectal cancer risk; colorectal cancer screening; commercialization; cost; cost effective; follow-up; high risk; low and middle-income countries; metabolomics; microcosting; mortality; patient stratification; point of care; point-of-care diagnostics; portability; premalignant; prevent; programs; prospective; rectal; screening; time use; validation studies

PROJECT SUMMARY/ABSTRACT Colorectal cancer (CRC) has become a major public health issue in low- and middle-income countries (LMIC); globally, it is the third most common cancer. Colorectal cancer rates are rising in LMICs. Outcomes of patients with CRC are poor in LMICs, largely because patients have advanced disease. Colorectal cancer screening lowers mortality by identifying precancerous polyps (which can be removed) and diagnosing cancer at an early stage. In high-income countries (HIC), screening modalities include stool-based tests and endoscopies. Due to cost, high incidence of benign rectal bleeding, limited access, and lack of point of care (POC) options, these tests are rarely used in LMICs. The large majority of patients at high-risk for CRC in LMIC do not undergo any CRC testing. Thus, there is an unmet need for a cost-effective CRC diagnostic to identify patients at higher risk for CRC and polyps, thereby minimizing the number of costly negative colonoscopies. We propose using the research network we have built in Nigeria to implement a unique urine-based POC metabolomics test that can be performed in centers in LMICs to diagnose patients with early-stage CRC and/or precancerous polyps. Our goal is to validate our sensitive, affordable handheld biosensor device. We have shown that our 14-metabolite urine test sensitivity is 82.3% for polyp diagnosis and 95% for CRC diagnosis. During the UG3 phase, using urine from 450 Nigerian patients (150 with CRC, 150 with polyps, and 150 with normal colons), we will refine our metabolite signature to 3 metabolites and modify the biosensor to make it highly sensitive for Nigerian patients. During the UH3 phase, we will pilot test the biosensor device in Nigeria with 75 patients with CRC, polyps, and normal colons. We will then use the POC in real-time on urine from 645 patients >40 years of age with rectal bleeding, with a family history of CRC, or with a personal diagnosis of CRC. All patients will then receive a colonoscopy. Microcosting will be conducted to inform a cost-effective analysis, based on World Health Organization thresholds for cost-effective or very cost-effective, of the POC testing for each study group at the current projected price. Finally, we will determine beliefs and barriers related to urine testing for CRC. Our team is comprised of experts in CRC screening and management in HICs and LMICs (Memorial Sloan Kettering [MSK], Obafemi Awolowo University [OAU], and University of Alberta [UA]). Memorial Sloan Kettering and OAU have collaborated on 2 prospective studies. We also have experts in metabolomics, engineering, development of biosensor POC tests, and manufacturing and marketing of medical devices (UA and Metabolomics Technologies, Inc.). To ensure the device is appropriate for the Nigerian health system and global CRC guidelines, we have created an advisory committee with cancer care, CRC screening, and medical device development experts. Our POC biosensor will reduce CRC mortality in LMICs, where there are currently no alternatives.

项目摘要/摘要 结直肠癌(CRC)已成为中低收入国家(LMIC)的主要公共卫生问题； 在全球范围内，它是第三种最常见的癌症。LMIC中的结直肠癌发病率正在上升。病人的转归 结直肠癌患者的LMIC较差，很大程度上是因为患者患有晚期疾病。结直肠癌筛查 通过识别癌前息肉(可以切除)并及早诊断癌症来降低死亡率 舞台。在高收入国家，筛查方式包括基于粪便的检测和内窥镜检查。由于 成本、良性直肠出血的高发生率、有限的通路以及缺乏护理点(POC)选项，这些因素 测试很少在LMIC中使用。在LMIC中，绝大多数结直肠癌高危患者没有接受任何 CRC测试。因此，对具有成本效益的CRC诊断以识别患者的需求尚未得到满足 结直肠癌和息肉的风险更高，从而最大限度地减少昂贵的阴性结肠镜检查的数量。 我们建议使用我们在尼日利亚建立的研究网络来实施独特的基于尿液的POC 可以在LMICs的中心进行的代谢组学测试，以诊断早期结直肠癌和/或患者 癌前息肉。我们的目标是验证我们灵敏、实惠的手持生物传感器设备。我们有 我们的14代谢物尿检对息肉诊断的敏感性为82.3%，对结直肠癌的诊断敏感性为95%。 在UG3阶段，使用450名尼日利亚患者的尿液(150名结直肠癌患者，150名息肉患者和150名 ，我们将把我们的代谢物特征提炼为3种代谢物，并修改生物传感器以使其 对尼日利亚患者高度敏感。在UH3阶段，我们将在尼日利亚对生物传感器设备进行试点测试 75例结直肠癌、息肉和正常结肠患者。然后，我们将对645起的尿液实时使用PoC 40岁有直肠出血、有结直肠癌家族史或个人诊断为结直肠癌的患者。 CRC。然后所有患者都将接受结肠镜检查。将进行微观成本计算，以告知具有成本效益的 基于世界卫生组织对具有成本效益或非常成本效益的POC的阈值的分析 按当前预计价格为每个研究小组进行测试。最后，我们将确定信念和障碍 与结直肠癌的尿液检测有关。 我们的团队由HIC和LMIC(纪念斯隆)的CRC筛查和管理专家组成 凯特林[MSK]、Obafemi Awolowo大学[非统组织]和艾伯塔大学[UA])。纪念斯隆·凯特林 和非统组织合作进行了两项前瞻性研究。我们也有代谢组学、工程学、 开发生物传感器POC测试，以及医疗器械的制造和营销(UA和 代谢组学技术公司)。以确保该设备适用于尼日利亚的卫生系统，并 根据全球CRC指南，我们创建了一个咨询委员会，负责癌症护理、CRC筛查和医疗 设备开发专家。我们的POC生物传感器将降低LMIC中的CRC死亡率， 目前没有其他选择。