Leveraging Medicare Linkages to Identify New Associations: Prescription Drugs and Digestive Cancer Risk

利用医疗保险联系来确定新的关联：处方药和消化道癌症风险

基本信息

批准号：
10425077
负责人：
Katsiaryna Bykov
金额：
$ 48.8万
依托单位：
SLOAN-KETTERING INST CAN RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-22 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10425077
关键词：
Accounting Address Adult Aging Antineoplastic Agents Benefits and Risks Calibration Chemopreventive Agent Clinical Trials Colorectal Data Data Set Databases Detection Development Disease Drug Prescriptions Drug usage Elderly Epidemiology Goals Health High Prevalence Hybrids Individual Inflammatory Investments Link Liver Long-Term Effects Malignant Neoplasms Medicare Metabolic Metabolism National Cancer Institute Organ Oropharyngeal Outcome Pancreas Pathway interactions Persons Pharmaceutical Preparations Phase Population Population Heterogeneity Predisposition Prevalence Research Resources Risk Role SEER Program Sample Size Scanning Signal Transduction Site Source Stomach Surveys Testing Tissues Translations United States National Institutes of Health Validation absorption active comparator beneficiary cancer risk cancer site carcinogenicity case control cohort design follow-up genome wide association study human old age (65+)innovation interest novel novel anticancer drug novel therapeutics power analysis protective effect

项目摘要

PROJECT SUMMARY Nearly 90% of US adults ages 65 and older use prescription drugs; however, surprisingly little is known about the long-term health effects of these drugs beyond the conditions for which they are indicated. Such unforeseen risks and benefits, particularly for diseases with a long latency period, such as cancer, are not well suited to detection in clinical trials, given that such trials are inadequate in size and duration of follow-up to detect drug-cancer associations. Multiple lines of evidence suggest that use of common prescription drugs may influence the development of various digestive cancers. However, prior studies have largely focused on broad, common classes of drugs, rather than individual drugs. The availability of Medicare linkages—featuring an extremely large diverse population of older adults, detailed prescription drug data, and follow-up for cancer outcomes—enables the comprehensive scan of associations between individual drugs and cancer risk. Given the high prevalence of prescription drug use among older adults and increased risk of cancer in this group, it is especially critical to understand the long-term effects of prescription drugs in aging populations. We will leverage data from the National Cancer Institute Surveillance, Epidemiology, and End Results Program (SEER)-Medicare linked database to discover and follow-up novel associations between prescription drugs and risk of digestive cancer, both overall and specific to the five most common digestive sites (colorectum, pancreas, stomach, oropharynx, and liver). First, we will conduct a Drug-Wide Association Study (‘DrugWAS’) to identify associations between prescription drugs and risk of digestive cancers, using bootstrapping to correct for multiple testing. Second, we will assess the influence of potential confounding by indication by evaluating whether the associations hold when compared directly to drugs taken for the same indication. For associations that remain after applying the steps above, we will perform propensity score calibration using additional data from the Medicare Current Beneficiary Survey (MCBS); this will allow us to estimate associations after accounting for additional sources of confounding. Our proposed hybrid approach—integrating a hypothesis-free framework with careful adjustment for multiple testing and confounding—will identify novel drug signals in older adults and further refine these signals to those that withstand correction for multiple testing and adjustment for confounding. This exploratory study will generate hypotheses of novel drug-cancer associations as well as provide impetus for follow-up in resource- intensive settings. Moreover, we will provide proof of principle for a multi-phased approach that leverages large publicly available datasets created through decades of NIH investment to identify novel and meaningful cancer associations; this approach can be applied in long-term surveillance efforts of drug effects on health.

项目摘要在65岁及以上的美国成年人中，有近90％使用处方药；这些药物的长期健康影响超出了指示的条件。不可预见的风险和利益，特别是对于长期潜伏期的疾病，不好鉴于此类试验的大小和持续时间不足，适合在临床试验中检测检测毒品癌的协会。影响各种消化癌的发展。常见的药物，而不是单独的药物。多样化的老年人种群，详细的处方药数据和癌症的随访结果 - 可以全面扫描单个药物与癌症风险之间的关联。老年人处方药使用的高流行率和这一组癌症的风险增加对于了解处方药在衰老人群中的长期影响特别至关重要。我们将利用国家癌症研究所监视，流行病学和最终结果计划的数据（SEER） - Medicare链接数据库，以发现和随访处方药之间的新型关联以及消化癌的风险，无论是五种最常见的消化系统的总体和特异胰腺，胃，口咽和肝脏）。确定处方药之间的关联和消化癌的风险，使用自举纠正第二个测试。关联是否直接与同样适应症的药物进行比较时。在应用上述步骤后，我们将使用其他数据执行倾向得分校准从Medicare当前的受益人调查（MCB）考虑了其他混淆来源。我们的支撑混合方法融入了一个无假设的框架，并仔细调整多个测试和混淆 - 会在老年人中确定新型药物信号，并进一步完善信号那些承受多次测试和调整的校正。产生新型药物关联的假设，并为资源的随访提供动力此外，我们将为多个附带提供原理证明通过数十年的NIH投资创建的公开可用数据集，以识别Novy和有意义的癌症协会可以将这种方法应用于药物对健康的影响。