本综述的目的是总结和评估药物流行病学研究的研究方法、新发现和未来方向，评估药物治疗对不同虚弱程度老年人的益处和危害。体弱的老年人健康状况不佳和药物治疗产生不良反应的风险较高。然而，由于体弱老年人的入组不足以及临床试验中缺乏经过验证的虚弱评估，目前的证据有限。最近在管理索赔和电子健康记录（数据库衍生的虚弱评分）测量虚弱方面取得的进展使研究人员能够识别虚弱的患者，并使用常规医疗保健数据根据患者的虚弱程度评估治疗效果的异质性。在选择数据库衍生的衰弱评分时，研究人员必须考虑数据类型（例如，不同的编码系统）、预测因子评估周期的长度、针对临床验证的衰弱测量的验证程度，以及由于以下原因而产生的监测偏差的可能性：获得护理的机会不平等。我们回顾了 2013 年至 2023 年在 PubMed 上发表的 13 项药物流行病学研究，这些研究根据虚弱程度评估了心血管药物、糖尿病药物、抗肿瘤药物、抗精神病药物和疫苗的益处和危害。这些研究表明，虽然更严重的虚弱与不良治疗结果呈正相关，但虚弱的老年人仍然可以从药物治疗中受益。因此，我们建议在药物流行病学研究中常规进行衰弱亚组分析。尽管数据和设计存在局限性，但此类研究的结果可能会为整个衰弱谱系的老年人制定药物治疗提供信息。© 2024。作者，获得 Springer Nature Switzerland AG 的独家许可。

The objective of this review is to summarize and appraise the research methodology, emerging findings, and future directions in pharmacoepidemiologic studies assessing the benefits and harms of pharmacotherapies in older adults with different levels of frailty. Older adults living with frailty are at elevated risk for poor health outcomes and adverse effects from pharmacotherapy. However, current evidence is limited due to the under-enrollment of frail older adults and the lack of validated frailty assessments in clinical trials. Recent advancements in measuring frailty in administrative claims and electronic health records (database-derived frailty scores) have enabled researchers to identify patients with frailty and to evaluate the heterogeneity of treatment effects by patients' frailty levels using routine health care data. When selecting a database-derived frailty score, researchers must consider the type of data (e.g., different coding systems), the length of the predictor assessment period, the extent of validation against clinically validated frailty measures, and the possibility of surveillance bias arising from unequal access to care. We reviewed 13 pharmacoepidemiologic studies published on PubMed from 2013 to 2023 that evaluated the benefits and harms of cardiovascular medications, diabetes medications, anti-neoplastic agents, antipsychotic medications, and vaccines by frailty levels. These studies suggest that, while greater frailty is positively associated with adverse treatment outcomes, older adults with frailty can still benefit from pharmacotherapy. Therefore, we recommend routine frailty subgroup analyses in pharmacoepidemiologic studies. Despite data and design limitations, the findings from such studies may be informative to tailor pharmacotherapy for older adults across the frailty spectrum.© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.