Establishing Clinical Feasibility of the Raman Assay for Colorectal Cancer

 描述(由申请人提供)：2014年Tibbetts奖获得者ChemImage Corporation与胃肠协会和阿勒格尼消化健康中心合作，提出了一种基于高通量拉曼分子成像(RMI)光谱的结直肠癌(CRC)诊断的颠覆性技术，称为结直肠癌拉曼检测(RACC)。RMI涉及使用有监督的多变量统计分析(即化学计量学)技术收集和评估空间分辨的拉曼光谱。在初步的初步研究中，RACC已经能够在不使用化学试剂的情况下检测干燥的血清成分和蛋白质构象的细微变化。RACC可以区分来自结直肠癌患者和无疾病患者的生物库血清样本，敏感度和特异度约为90%。到目前为止进行的初步研究表明，RACC对早期结直肠癌和息肉(包括晚期腺瘤)的存在是敏感的，如果在技术和临床上被证实是可行的，RACC将作为结直肠癌体外诊断(IVD)的筛查方法具有商业价值。在这个与国家癌症研究所的使命相关的拟议项目中，ChemImage预计将首次展示RACC应用于新鲜临床血清样本的技术和临床可行性。RACC检测的长期目标和预期用途将作为筛查癌前息肉和结直肠癌患者的辅助手段。RACC测试将由筛查结直肠癌的卫生保健专业人员使用，包括胃肠病专家和初级保健医生。在这项第一阶段的研究中，RMI光谱将在低通量下使用785 nm激光激发的拉曼显微镜进行，而不使用试剂。在其成熟的商业形式下，RACC测试将在高通量RACC仪器上进行，该仪器采用自动化检测算法和软件，每干血清样本5分钟，以最大限度地降低每次检测的成本。如果作为CRC筛查试验的预期用途得到验证，我们预计RACC将通过食品和药物管理局(FDA)的上市前批准(PMA)，并将要求医疗保险和医疗补助服务中心(CMS)做出全国覆盖决定。ChemImage已经组建了一个监管事务和报销顾问组，成员包括在FDA、CDRH、IVD和放射健康办公室和CMS拥有多年经验的经验丰富的顾问，他们的目标是增加成功商业化的可能性。RACC具有以与粪便潜血测试(FOBT)相当的成本提供接近结肠镜检查的检测性能的潜力，因为它不使用昂贵的试剂。由于RACC将适用于血清样本，预计在目标患者人群中有非常高的遵从率，因此提高了护理质量，并降低了管理结直肠癌的成本。同样具有重要意义的是，由于结直肠癌对非裔美国人患者的影响不成比例，这种检测方法的成功开发将有助于缩小这种医疗差距。

 DESCRIPTION (provided by applicant): ChemImage Corporation, a 2014 Tibbetts Award recipient, in collaboration with GastroIntestinal Associates and the Allegheny Center for Digestive Health, proposes a disruptive technology based on high throughput Raman Molecular Imaging (RMI) spectroscopy for colorectal cancer (CRC) diagnosis called the Raman Assay for Colorectal Cancer (RACC). RMI involves the collection and evaluation of spatially resolved Raman spectra using supervised multivariate statistical analysis (i.e. chemometric) techniques. In preliminary Pilot Studies, RACC has been able to detect subtle changes in dried blood serum composition and protein conformation without the use of chemical reagents. RACC can differentiate between biobanked blood serum samples from patients with colorectal cancer versus those who are disease free with sensitivity and specificity of approximately 90%. Pilot studies conducted to date suggest RACC is sensitive to early stage CRC and the presence of polyps, including advanced adenomas, and if validated as technically and clinically feasible, RACC would have commercial value as a CRC screening in vitro diagnostic (IVD) assay. In this proposed project which is relevant to the mission of the National Cancer Institute, ChemImage anticipates undertaking the first demonstration of the technical and clinical feasibility of RACC applied to fresh clinical blood serum samples. The longer term objective and intended use of the RACC Test will be as an aid in screening patients for pre-cancerous polyps and CRC. The RACC Test will be used by health care professionals who screen for CRC, including gastroenterologists and primary care physicians. In this Phase 1 study, RMI spectroscopy will be performed at low throughput using a Raman microscope operating with 785nm laser excitation without the use of reagents. In its mature commercial form, the RACC Test would be performed on a high throughput RACC instrument enabled by automated detection algorithms and software in =5 min per dried blood serum sample to minimize cost per assay. If validated for Intended Use as a CRC screening assay, we anticipate RACC will undergo Food and Drug Administration (FDA) premarket approval (PMA) and will require Centers for Medicare & Medicaid Services (CMS) National Coverage Decision. ChemImage has assembled a Regulatory Affairs & Reimbursement Advisory Group, with participation of experienced consultants having years of past experience within the FDA, CDRH, Office of IVD & Radiological Health, and CMS, whose goal is to increase the likelihood of successful commercialization. RACC has the potential to provide the detection performance approaching colonoscopy at costs comparable to fecal occult blood tests (FOBT), because it operates without the use of costly reagents. Since RACC would be applicable to blood serum samples, it is anticipated to have a very high compliance rate among target patient populations, and as a result improve the quality of care, and reduce the cost of managing CRC disease. Also of significance, as CRC disproportionally affects African American patients, the successful development of this assay would help reduce this healthcare disparity.