Clinical Importance of Drug-Drug Interactions

描述(由申请人提供)：药物-药物相互作用(DDIS)是一个重大的临床和公共卫生负担，特别是对老年人。随着人口老龄化和多元制药化程度的增加，这一负担将进一步增加。有关DDIS的知识来自许多来源，严格的基于人群的临床结果研究提供了最有用的临床信息。因为很少进行人群DDI研究，所以DDI汇编之间对于哪些药物对导致临床上重要的DDIS存在严重的分歧。此外，哪些潜在的DDI在临床上很重要，这一点还不确定 阻碍了减轻DDIS影响的努力，例如计算机化的决策支持。因此，迫切需要对DDIS的临床效应进行人群研究，并应将其与DDIS的生物学基础研究结合起来。在这一更新申请中，我们建议以两种重要和创新的方式将我们的方法扩展到人口DDI研究：1)积极和明确地纳入机械性考虑；2)实施一种顺序方法，初步识别和量化风险，然后在必要的情况下，根据这一步骤，进一步确定重要的DDI的特征，目标是为未来的工作提供基础，以降低风险。基于确定研究重点的广泛和结构化的咨询过程，我们建议使用5个州的大型医疗补助/医疗保险数据集进行一系列人口DDI研究。这些研究将检验涉及降脂药物、抗凝血药物和口服抗糖尿病药物的假设相互作用，这三类药物与老年人密切相关，并具有导致临床重要DDIS的高可能性。因此，我们将研究具有重大临床和公共卫生重要性的潜在DDIS，特别是对老年人，并在此过程中开发有助于阐明这些潜在DDIS的机制的数据。 公共卫生相关性：药物-药物相互作用(DDIS)是一个重大的临床和公共卫生负担，特别是对老年人来说。然而，对大多数潜在的DDIS的临床重要性知之甚少。我们将对潜在的DDIS影响降脂、抗凝和抗糖尿病治疗的临床重要性进行大规模人群研究，解决具有重大临床和公共卫生重要性的潜在DDIS。

DESCRIPTION (provided by applicant): Drug-drug interactions (DDIs) are a significant clinical and public health burden, especially for older adults. This burden will increase further as the population ages and the degree of polypharmacy increases. Knowledge about DDIs comes from many sources, with rigorous population-based studies of clinical outcomes providing the most clinically useful information. Because very few population DDI studies have been performed, there is profound disagreement among the DDI compendia about which drug pairs cause clinically important DDIs. Further, uncertainty about which potential DDIs are clinically important has hampered efforts to mitigate the effects of DDIs, such as computerized decision support. Population studies of the clinical effects of DDIs are therefore badly needed, and should be integrated with research on the biological basis of DDIs. In this renewal application, we propose to extend our approach to population DDI studies in two important and innovative ways: 1) by actively and explicitly incorporating mechanistic considerations; and 2) by implementing a sequential approach of initially identifying and quantifying risk, then, where warranted based on this step, characterizing important DDIs further, with the goal of providing the basis for future efforts to mitigate risk. Based on an extensive and structured consultative process to identify research foci, we propose to conduct a series of population DDI studies using a large 5-state Medicaid/Medicare dataset. These studies will examine hypothesized interactions involving lipid lowering drugs, anti-clotting drugs, and oral anti-diabetic drugs, three drug classes with enormous relevance for older adults, and with high potential for causing clinically important DDIs. Thus, we will study potential DDIs of great clinical and public health importance, especially to older adults, and in the process develop data that will help elucidate the mechanisms of these potential DDIs. PUBLIC HEALTH RELEVANCE: Drug-drug interactions (DDIs) are a significant clinical and public health burden, especially for older adults. However, little is known about the clinical importance of most potential DDIs. We will conduct large population studies of the clinical importance of potential DDIs affecting lipid lowering, anti-clotting, and anti-diabetic therapies, addressing potential DDIs of great clinical and public health importance.