Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
Pharmacoepidemiol Drug Saf. 2020 Aug;29(8):939-950. doi: 10.1002/pds.5071. Epub 2020 Jul 13.
In pharmacoepidemiologic studies, estimating medication adherence, persistence, and exposure patterns is critical. Constructing medication treatment episodes from prescription claims data involves assumptions related to grace period, carry-over, and lag effect, but there are no guidelines for these assumptions. We evaluated reporting and variability of these parameters in pharmacoepidemiology studies, using a case study of antihyperglycemic medications and major adverse cardiovascular events (MACE).
We conducted a systemic review using MEDLINE and EMBASE for studies published prior to January 2, 2020 comparing the risk of MACE between dipeptidyl peptidase 4 (DPP-4) inhibitors and active comparators. We extracted study characteristics and results, including grace period, carry-over, and lag effect. Risk of bias was assessed by the Newcastle-Ottawa scale, and assessments for prevalent user, immortal time, time lag, and time window biases.
A total of 14/1850 studies identified were included. Grace period was not reported in 5 (35.7%) studies and ranged from 0 days to 180 days when reported. Carry-over was not reported in 10 studies (71.4%). Lag effect was not reported in nine (71.4%) studies and ranged from 0 days to 180 days when reported. No studies conducted sensitivity analyses examining the effects of these assumptions on study findings. Predominant biases were inadequate follow-up time, comparability of cohorts, prevalent use, and lag time bias.
Use of grace period, carry-over, and lag effect were poorly reported and highly variable. Future pharmacoepidemiology studies should improve reporting, justify ranges for these parameters, and conduct sensitivity analyses to evaluate effects of these assumptions.
在药物流行病学研究中，评估药物的依从性、持续性和暴露模式至关重要。从处方索赔数据构建药物治疗期涉及与宽限期、延续效应和滞后效应相关的假设，但这些假设没有指南。我们使用抗高血糖药物和主要不良心血管事件（MACE）的案例研究评估了这些参数的报告和变异性。
我们使用 MEDLINE 和 EMBASE 进行了系统综述，检索了截至 2020 年 1 月 2 日之前发表的比较二肽基肽酶 4（DPP-4）抑制剂与活性对照药物治疗 MACE 风险的研究。我们提取了研究特征和结果，包括宽限期、延续效应和滞后效应。使用纽卡斯尔-渥太华量表评估偏倚风险，并评估了现患用户、不朽时间、时间滞后和时间窗口偏倚。
共纳入 14/1850 项研究。5 项（35.7%）研究未报告宽限期，报告的宽限期范围为 0 天至 180 天。10 项（71.4%）研究未报告延续效应。9 项（71.4%）研究未报告滞后效应，报告的滞后效应范围为 0 天至 180 天。没有研究进行敏感性分析，以检查这些假设对研究结果的影响。主要偏倚包括随访时间不足、队列可比性、现患使用和滞后时间偏倚。
宽限期、延续效应和滞后效应的使用报告不佳且差异很大。未来的药物流行病学研究应改善报告，为这些参数确定合理的范围，并进行敏感性分析，以评估这些假设的影响。
