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: 9221852
• 负责人: OLUSEGUN ISAAC ALATISE
• 金额: $ 40.58万
• 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 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9221852
• 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 risk; Patient-Focused Outcomes; Patients; Phase; Physicians; Polyps; Population; Precancerous Polyp; Premalignant; 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 screening; commercialization; cost; cost effective; follow-up; high risk; low and middle-income countries; metabolomics; mortality; patient stratification; point of care; point-of-care diagnostics; portability; 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，它是第三大常见的癌症。 LMIC的结直肠癌率正在上升。患者的结果 CRC的LMIC较差，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（可以去除）并在早期诊断癌症来降低死亡率 阶段。在高收入国家（HIC）中，筛查方式包括基于凳子的测试和内窥镜。由于 成本，良性直肠出血的高发病率，有限的访问和缺乏护理点（POC）选项，这些 测试很少在LMIC中使用。 LMIC中CRC高危患者的绝大多数患者不会接受任何 CRC测试。因此，未满足的需要具有成本效益的CRC诊断来识别患者 CRC和息肉的风险更高，从而最大程度地减少了昂贵的负面结肠镜检查的数量。 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LMIC中心进行的代谢组学测试，以诊断早期CRC和/或患者 癌性息肉。我们的目标是验证我们敏感，负担得起的手持生物传感器设备。我们有 表明，我们的14米代谢物尿液测试灵敏度为82.3％，CRC诊断为95％。 在UG3阶段，使用450名尼日利亚患者的尿液（150例CRC，150个息肉，150，150 普通结肠），我们将使我们的代谢产物签名完善到3个代谢物，并修改生物传感器以实现它 对尼日利亚患者高度敏感。在UH3阶段，我们将试行测试尼日利亚的生物传感器设备 有75例CRC，息肉和正常结肠患者。然后，我们将在645的尿液上实时使用POC > 40岁的直肠出血，具有CRC家族史或个人诊断的患者 CRC。然后所有患者将接受结肠镜检查。将进行微骨架，以告知一个成本效益 基于世界卫生组织的分析，以具有成本效益或具有成本效益非常有效的世界卫生组织阈值 以当前的预计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的尿液测试有关。 我们的团队由HICS和LMICS的CRC筛查和管理专家组成（纪念Sloan Kettering [MSK]，Obafemi Awolowo大学[OAU]和艾伯塔大学[UA]）。纪念斯隆·凯特林（Sloan Kettering） OAU已经合作进行了2项前瞻性研究。我们还拥有代谢组学，工程学， 开发生物传感器POC测试以及医疗设备的制造和营销（UA和 代谢组学技术公司）。确保该设备适合尼日利亚卫生系统和 全球CRC指南，我们通过癌症护理，CRC筛查和医疗成立了一个咨询委员会 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。