Centre for Clinical Epidemiology & Evaluation, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.
Pharmacoepidemiol Drug Saf. 2022 Jan;31(1):13-21. doi: 10.1002/pds.5372. Epub 2021 Oct 29.
In drug safety and effectiveness studies based on secondary data, the choice of an appropriate exposure measure for a given outcome can be challenging. Different measures of exposure can yield different estimates of treatment effect and safety. There is a knowledge gap with respect to developing and refining measures of drug exposure, to ensure that the exposure measure addresses the study question and is suitable for statistical analysis.
We present a transparent, step-by-step approach to the development of drug exposure measures involving secondary data. This approach would be of interest to students and investigators with initial training in pharmacoepidemiology. We illustrate the approach using a study about Parkinson's disease.
We described the exposure specifications according to the study question. Next, we refined the exposure measure by linking it to knowledge about four major concepts in drug safety and effectiveness studies: drug use patterns, duration, timing, and dose. We then used this knowledge to guide the ultimate choice of exposure measure: time-varying, cumulative 6-month exposure to tamsulosin (a drug used to treat prostate hyperplasia).
The proposed approach links exposure specifications to four major concepts in drug safety and effectiveness studies. Formulating subject-matter knowledge about these major concepts provides an avenue to develop the rationale and specifications for the exposure measure.
在基于二次数据的药物安全性和有效性研究中，选择合适的暴露测量指标对于特定结局可能颇具挑战。不同的暴露测量指标可能会产生不同的治疗效果和安全性估计值。在开发和完善药物暴露测量指标方面，存在着知识空白，以确保暴露测量指标能够解决研究问题并适合统计分析。
我们提出了一种涉及二次数据的药物暴露测量指标开发的透明、逐步方法。对于初步接受药物流行病学培训的学生和研究人员来说，这种方法可能会引起兴趣。我们使用一项关于帕金森病的研究来举例说明该方法。
我们根据研究问题描述了暴露规范。接下来，我们通过将其与药物安全性和有效性研究中的四个主要概念（药物使用模式、持续时间、时间和剂量）的知识联系起来，对暴露指标进行了细化。然后，我们利用这些知识来指导最终暴露指标的选择：即时间变化的、累积的 6 个月坦索罗辛（一种用于治疗前列腺增生的药物）暴露。
所提出的方法将暴露规范与药物安全性和有效性研究中的四个主要概念联系起来。制定关于这些主要概念的主题知识为制定暴露指标的基本原理和规范提供了途径。
