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

• 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
• 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

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 近90%的65岁及以上的美国成年人使用处方药;然而，令人惊讶的是， 这些药物的长期健康影响超出了它们所适用的条件。等 不可预见的风险和收益，特别是对于潜伏期较长的疾病，如癌症， 适合在临床试验中检测，因为此类试验的规模和随访时间不足， 检测药物与癌症的关联多种证据表明，使用普通处方药可能 影响各种消化道癌症的发展。然而，先前的研究主要集中在广泛的， 药物种类，而不是单个药物。Medicare链接的可用性-具有 非常大的不同老年人群体，详细的处方药数据和癌症随访 结果-能够全面扫描个体药物和癌症风险之间的关联。给定 老年人中处方药使用的高流行率和这一群体患癌症的风险增加， 对于了解处方药在老龄化人群中的长期影响尤为重要。 我们将利用国家癌症研究所监测、流行病学和最终结果项目的数据 （SEER）-Medicare链接数据库，用于发现和跟踪处方药之间的新关联 和消化道癌症的风险，无论是总体还是特定于五个最常见的消化部位（结直肠， 胰腺、胃、口咽和肝脏）。首先，我们将进行药物广泛关联研究（DrugWAS） 确定处方药和消化道癌症风险之间的关联，使用自助法纠正 进行多次测试。其次，我们将通过评估适应症来评估潜在混杂的影响， 当直接与用于相同适应症的药物进行比较时，相关性是否成立。为社团 在应用上述步骤后，我们将使用其他数据进行倾向评分校准 医疗保险当前受益人调查（MCBS）;这将使我们能够估计 考虑到额外的混杂源。 我们提出的混合方法-整合一个无假设的框架，并仔细调整多个 测试和混淆-将确定老年人的新药物信号，并进一步完善这些信号， 那些经受多次测试校正和混杂调整的。这项探索性研究将 产生新的药物-癌症关联的假设，并为后续资源提供动力， 密集设置。此外，我们将为多阶段方法提供原理证明，该方法利用了大量 通过NIH数十年的投资创建的公开数据集，以识别新的和有意义的癌症 这种方法可以应用于药物对健康影响的长期监测工作。