Diabetes, Medications and the Cost-Effectiveness of Screening for Colorectal Neoplasia

项目摘要/摘要：应聘者的长期职业目标是成为一名独立调查员 在癌症流行病学、生物医学信息学、药物流行病学和 健康经济建模与评价。有重点的教学培训、指导和体验式学习 通过本奖项建议的研究活动，将促进在追求以下目标的关键技能的发展 告知和改进癌症预防和筛查的知识。这位候选人的研究动机是 认识到2型糖尿病(T2 DM)患者患结直肠癌的风险增加30%-40% 癌症(CRC)，而抗糖尿病药物也可能改变CRC的风险。因此，这一高风险群体呈现出 提供有针对性的筛查和早期发现结直肠癌的机会。目前，结直肠癌筛查是根据年龄和 家族史，不考虑包括T2 DM在内的合并症。以她以前在癌症方面的工作为基础 流行病学，候选人寻求确定T2 DM与结直肠息肉风险之间的关联： 总体而言，按亚型和病变严重程度分类，分别反映不同的分子途径(目标1)； 检查与抗糖尿病治疗相关的结直肠息肉的风险：总体、按亚型和按病变 严重性(目标2)。这些目标将通过利用现有结肠镜检查的丰富资源来实现- 华盛顿大学医学中心(UWMC)胃肠病诊所建立的队列 2003-2011年间。人口统计学、选定的生活方式因素和详细的组织病理学 摘自UWMC的电子病历(EMR)数据库。候选人提议延长这一期限 队列到2017年(N~38,000)，并通过将现有数据与糖尿病相关变量从 使用生物医学信息学(例如，自然语言处理、临床文本挖掘)的电子病历数据库 评估结直肠肿瘤的风险。使用从目标1和目标2得出的这些经验估计， 候选人随后将建立一个微观模拟模型，预测T2 DM患者发生结直肠肿瘤的风险， 解释了他们的糖尿病治疗。替代筛查和治疗策略，包括改变 在T2 DM患者中筛查开始年龄、修改糖尿病治疗或改变筛查方式将是 对其成本效益进行评估(目标3)。这项工作可能有助于提供有针对性的筛查建议。 这反过来可以降低T2 DM患者中结直肠癌的发病率和死亡率，并提高成本- 结直肠癌筛查的有效性。候选人提出了一项培训和职业发展计划， 她在癌症流行病学方面的先前技能基础上获得了在生物医学信息学方面的经验和熟练程度， 药物流行病学、卫生经济建模和评估，包括成本效益 接近了。由国家和国际专家组成的跨学科指导小组将 提供必要的专业知识，以确保此提案的成功，并促进候选人的 转变为癌症预防和筛查领域的独立翻译研究员。

Project Summary/Abstract: The candidate's long-term career goal is to become an independent investigator with transdisciplinary expertise in cancer epidemiology, biomedical informatics, pharmacoepidemiology, and health economic modeling and evaluation. The focused didactic training, mentorship, and experiential learning through research activities proposed in this award will facilitate the development of critical skills in the pursuit of knowledge to inform and improve cancer prevention and screening. The candidate's research is motivated by the recognition that type-2 diabetes mellitus (T2DM) patients are at a 30-40% increased risk for colorectal cancer (CRC), and that anti-diabetic drugs may also alter CRC risk. Thus, this high-risk group presents an opportunity for targeted screening and early detection of CRC. Currently, CRC screening is based on age and family history, with no consideration for comorbidities, including T2DM. Building on her previous work in cancer epidemiology, the candidate seeks to determine the association between T2DM and risk of colorectal polyps: overall, by subtypes, and by lesion severity, individually reflecting different molecular pathways (Aim 1); and to examine the risk for colorectal polyps associated with anti-diabetic therapy: overall, by subtypes, and by lesion severity (Aim 2). These aims will be addressed by leveraging the rich resources of an existing colonoscopy- based cohort at the University of Washington Medical Center's (UWMC) Gastroenterology clinic established during 2003-2011. Demographics, select lifestyle factors, and detailed histopathology have been previously abstracted from UWMC's electronic medical records (EMR) database. The candidate proposes to extend this cohort through 2017 (N~38,000), and enhance it by linking existing data with diabetes-related variables from the EMR database using biomedical informatics (e.g., natural language processing, clinical text mining) to estimate the risk for colorectal neoplasia. Using these empirical estimates derived from Aims 1 and 2, the candidate will then build a microsimulation model projecting the risk for colorectal neoplasia in T2DM patients, accounting for their diabetes therapy. Alternative screening and treatment strategies, including altering the screening start-age, modifying diabetes treatment, or altering screening modality among T2DM patients, will be evaluated for their cost-effectiveness (Aim 3). This work may help inform targeted screening recommendations that could, in turn, lower the incidence and mortality of CRC among persons with T2DM, and improve the cost- effectiveness of CRC screening. The candidate has proposed a training and career development plan that builds upon her prior skills in cancer epidemiology to gain experience and proficiency in biomedical informatics, pharmacoepidemiology, and health economic modeling and evaluation, including cost-effectiveness approaches. The transdisciplinary mentorship team, comprised of national and international experts, will provide the necessary expertise to ensure the success of this proposal, as well as facilitate the candidate's transition into an independent translational investigator in the field of cancer prevention and screening.