Clinical Importance of Drug-Drug Interactions

描述(由申请人提供)：药物-药物相互作用(DDIS)是一个重要的公共卫生问题，特别是在老年人中，他们是药物的最大消费者。几乎所有关于潜在DDIS临床重要性的现有知识都来自药代动力学研究或病例报告，这两种研究对识别临床上重要的DDIS的效用有限。因此，在大多数潜在的DDIS的临床重要性方面，标准的DDI参考文献之间存在着很大的分歧。寻求改善药物使用的系统性努力，如药物利用审查程序和计算机化医嘱输入，完全依赖于一套有效的临床规则，因此受到这种知识差距的严重阻碍。为了解决现有对DDIS临床重要性的认识上的这些关键差距，研究人员将对基于咨询临床医生和临床药剂师专家小组的正式程序选择的高优先级潜在DDIS进行受控流行病学研究。我们将使用和扩展现有的非常大的药物流行病学数据库，该数据库由来自五个大型项目的医疗补助数据组成，并辅之以医疗保险数据，以确保完全捕获老年人的结果，以及来自英国的全科医学研究数据库。我们将使用病历审查来检查我们结果衡量标准的有效性。我们的研究策略将包括嵌套病例对照和病例交叉设计，并将产生相对风险、风险差异和需要伤害的数量(NNH)。将研究与患者和治疗因素有关的相关不良后果。这项研究的结果将对公共卫生、临床护理和阐明DDIS的药理学具有重要意义，并将作为未来研究未记录在行政和医疗记录数据中的因素的基础。

DESCRIPTION (provided by applicant): Drug-drug interactions (DDIs) are an important public health problem, especially in the elderly, who are the largest consumers of medications. Nearly all existing knowledge about the clinical importance of potential DDIs comes from pharmacokinetic studies or case reports, both of which have limited utility for identifying clinically important DDIs. As a result, there is a great deal of disagreement among standard DDI reference texts regarding the clinical importance of most potential DDIs. Systematic efforts such as drug utilization review programs and computerized physician order entry that seek to improve medication use depend entirely upon a valid set of clinical rules, and are thus severely hampered by this knowledge gap. To address these critical gaps in existing knowledge of the clinical importance of DDIs, the investigators will perform controlled epidemiologic studies of high-priority potential DDIs that have been selected based on a formal process involving consultation with an Expert Panel of clinicians and clinical pharmacologists. We will use and expand upon an existing, very large pharmacoepidemiologic database consisting of Medicaid data from five large programs, supplemented by Medicare data to ensure complete capture of outcomes in the elderly, together with the General Practice Research Database from the UK. We will examine the validity of our outcome measures using medical record review. Our research strategy will include nested case-control and case-crossover designs, and will yield relative risks, risk differences, and number needed to harm (NNH). Patient and treatment factors associated with developing the adverse outcome of interest will be studied. The results of this study will have important implications for public health, clinical care, and the elucidation of the pharmacology of DDIs, and will serve as a basis for future studies examining factors not recorded in administrative and medical records data.