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.

项目总结/摘要 结直肠癌（CRC）已成为低收入和中等收入国家（LMIC）的主要公共卫生问题; 在全球范围内，它是第三大常见癌症。低收入国家的结直肠癌发病率正在上升。患者预后 在LMIC中，CRC的发病率很低，主要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）和早期诊断癌症来降低死亡率 阶段在高收入国家（HIC），筛查方式包括粪便检测和内窥镜检查。由于 成本，良性直肠出血的高发生率，有限的访问，以及缺乏床旁（POC）的选择，这些 LMIC中很少使用测试。LMIC中的大多数CRC高风险患者不接受任何治疗。 CRC测试。因此，存在对成本有效的CRC诊断的未满足的需求，以在不需要的情况下识别患者。 CRC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一种独特的基于尿液的POC 代谢组学测试，可以在LMIC的中心进行，以诊断早期CRC患者和/或 癌前息肉我们的目标是验证我们的灵敏，负担得起的手持生物传感器设备。我们有 结果表明，我们的14-代谢物尿液检测灵敏度为息肉诊断的82.3%和CRC诊断的95%。 在UG 3阶段，使用来自450名尼日利亚患者（150名CRC患者，150名息肉患者和150名 正常结肠），我们将把我们的代谢物特征细化为3种代谢物，并修改生物传感器以使其 对尼日利亚患者非常敏感。在UH 3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。然后我们将在645年的尿液中实时使用POC 年龄>40岁的直肠出血患者，有CRC家族史，或个人诊断为 《儿童权利公约》。所有患者将接受结肠镜检查。将进行微成本计算，以提供具有成本效益的 根据世界卫生组织的成本效益或非常成本效益阈值，对POC进行分析 以目前预计的价格对每个研究组进行测试。最后，我们将确定信念和障碍 与CRC尿检有关。 我们的团队由HIC和LMIC的CRC筛查和管理专家组成（Memorial Sloan Kettering [MSK]、Obafemi Awolowo大学[OAU]和阿尔伯塔大学[UA]）。Memorial Sloan Kettering 与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，以及制造和销售医疗器械（UA和 Metabolomics Technologies，Inc.）。确保该器械适用于尼日利亚卫生系统， 根据全球CRC指南，我们成立了一个咨询委员会，负责癌症护理、CRC筛查和医疗保健。 设备开发专家。我们的POC生物传感器将降低低收入国家的CRC死亡率， 目前没有替代品。