Determining medications associated with drug-induced pancreatic injury through novel pharmacoepidemiology techniques that assess causation

通过评估因果关系的新型药物流行病学技术确定与药物引起的胰腺损伤相关的药物

• 批准号: 10638247
• 负责人: Ravy Kuppalapalle Vajravelu
• 金额: $ 38.29万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10638247
• 关键词: Accounting; Address; Biological; Biometry; Case Study; Case/Control Studies; Classification; Clinical; Clostridium difficile; Computers; Controlled Study; Dangerousness; Data; Data Analyses; Data Mart; Data Science; Databases; Dose; Drug Prescriptions; Electronic Health Record; Electronics; Epidemiology; Etiology; Exhibits; Exposure to; Future; Genomics; Goals; Health; Health Personnel; Hospitalization; Incidence; Individual; Infection; Label; Life Style; Linear Regressions; Logistic Regressions; Medical; Medication Management; Methodology; Methods; Modernization; National Institute of Diabetes and Digestive and Kidney Diseases; Observational Study; Outcome; Pancreatic Injury; Pancreatitis; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Pharmacodynamics; Pharmacoepidemiology; Pharmacopoeias; Procedures; Public Health; Randomized, Controlled Trials; Recurrence; Reporting; Research; Research Design; Research Personnel; Retrospective cohort study; Specificity; Strategic Planning; Techniques; Time; Uncertainty; United States; Update; Veterans Health Administration; acute pancreatitis; chronic pancreatitis; clinical data warehouse; design; evidence base; experience; fundamental research; gastrointestinal; improved; individual patient; innovation; insight; interest; novel; patient health information; pharmacologic; pilot test; post-market; prevent; response; side effect; time use; usability

PROJECT SUMMARY Acute pancreatitis causes nearly 300,000 hospitalizations per year in the United States, and its rates are rising. One-third of cases are classified as having unknown cause, leaving patients vulnerable to repeated episodes because they do not know how to alter their lifestyles. Unexpected side effects of prescription medications may be responsible for acute pancreatitis cases with unknown cause. This situation is called drug-induced pancreatic injury (DIPI). Unfortunately, healthcare providers and medical researchers do not know which medications cause DIPI. This is because the majority of research about DIPI comes from descriptions of the experience of individual patients. While these are valuable for providing clues about medications that might cause DIPI, they do not account for other factors that could contribute to acute pancreatitis. Therefore, conclusions from this type of study may falsely label particular medications as dangerous. This may lead to reduced use of medications that are effective for the conditions that they treat, resulting in worse outcomes for patients. There is a critical need to determine which medications do and do not cause DIPI in order to prevent cases of acute pancreatitis and to continue patients on safe essential medications. The recent availability of electronic databases with health information and powerful computer processing has made it possible to study the effects of thousands of medications. Additionally, a new data analysis technique called pharmacopeia-wide association studies (PWAS) has improved the efficiency of these studies. Furthermore, PWAS can be combined with fundamental epidemiology principles to determine whether a study finding demonstrating a medication side effect is true or false. The overall objective of this proposal is to identify medications that cause DIPI by applying PWAS to two large databases of patient health information. Additionally, this proposal will combine PWAS with a research framework called the Bradford Hill criteria to distinguish medications that cause DIPI from false results. The specific aims of this proposal are (1) To identify medications that are strongly associated with DIPI, demonstrate dose response, and exhibit biologic plausibility by applying the PWAS framework to case-control studies; (2) To identify medications that demonstrate consistent temporality and specificity with DIPI through novel applications of the PWAS framework; (3) To identify replicable medication-DIPI associations by repeating Aims 1 and 2 using a second database; and (4) To develop and disseminate an interactive database to integrate the study findings for clinicians and investigators. This research is significant because it will improve patient outcomes by resolving clinical uncertainty about which medications should be stopped after acute pancreatitis and which essential medications are safe to continue. This research is innovative because it combines cutting-edge data analysis techniques with fundamental research principles to comprehensively identify medications that cause DIPI. These techniques will be applied to future studies that aim to identify medications that contribute to other medical conditions.

项目摘要 在美国，急性胰腺炎每年导致近30万住院，其速度正在上升。 三分之一的病例被归类为未知原因，使患者容易受到重复发作的影响 因为他们不知道如何改变自己的生活方式。处方药的意外副作用可能 负责急性胰腺炎病例未知原因。这种情况称为吸毒 胰腺损伤（DIPI）。不幸的是，医疗保健提供者和医学研究人员不知道哪个 药物引起二比。这是因为关于DIPI的大多数研究来自 个别患者的经验。尽管这些对于提供可能的药物线索很有价值 导致DIPI，它们不考虑可能导致急性胰腺炎的其他因素。所以， 这类研究的结论可能会错误地将特定药物标记为危险。这可能会导致 减少对它们治疗疾病有效的药物使用的使用，从而导致更糟的结果 患者。确定哪种药物可以和不会导致DIPI以防止 急性胰腺炎的病例，并继续患者使用安全的基本药物。最近的可用性 具有健康信息和功能强大的计算机处理的电子数据库使学习成为可能 数千种药物的影响。此外，一种称为Pharmacopeia wide的新数据分析技术 协会研究（PWA）提高了这些研究的效率。此外，PWA可以是 结合基本流行病学原则，以确定研究发现是否证明了 药物副作用是对还是错。该提案的总体目的是确定导致的药物 DIPI通过将PWA应用于两个大型患者健康信息数据库。此外，该建议将 将PWA与称为Bradford Hill标准的研究框架相结合，以区分药物 导致虚假结果的dipi。该提案的具体目的是（1）确定 与DIPI密切相关，证明剂量反应，并通过应用 PWAS框架进行病例对照研究； （2）确定表现出一致时间性的药物 通过DIPI的特异性通过PWAS框架的新应用； （3）识别可复制的 使用第二个数据库重复AIM 1和2通过重复AIM 1和2的药物相关性； （4）开发和 传播一个交互式数据库，以整合临床医生和研究人员的研究结果。这 研究很重要，因为它可以通过解决哪些临床不确定性来改善患者的预后 急性胰腺炎后应停止药物，并可以安全地继续使用。 这项研究具有创新性，因为它将尖端数据分析技术与基本相结合 研究原则可全面识别导致DIPI的药物。这些技术将被应用 未来的研究旨在鉴定有助于其他医疗状况的药物。