Using Quantitative Bias Analysis to Adjust for Misclassification of COVID-19 Outcomes: An Applied Example of Inhaled Corticosteroids and COVID-19 Outcomes.

IF 2.4 4区医学 Q3 PHARMACOLOGY & PHARMACY

Pharmacoepidemiology and Drug Safety Pub Date : 2025-01-01 DOI:10.1002/pds.70086

Marleen Bokern, Christopher T Rentsch, Jennifer K Quint, Jacob Hunnicutt, Ian Douglas, Anna Schultze

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引用次数: 0

Abstract

Background: During the pandemic, there was concern that underascertainment of COVID-19 outcomes may impact treatment effect estimation in pharmacoepidemiologic studies. We assessed the impact of outcome misclassification on the association between inhaled corticosteroids (ICS) and COVID-19 hospitalisation and death in the United Kingdom during the first pandemic wave using probabilistic bias analysis (PBA).

Methods: Using data from the Clinical Practice Research Datalink Aurum, we defined a cohort with chronic obstructive pulmonary disease (COPD) on 1 March 2020. We compared the risk of COVID-19 hospitalisation and death among users of ICS/long-acting β-agonist (LABA) and users of LABA/LAMA using inverse probability of treatment weighted (IPTW) logistic regression. We used PBA to assess the impact of non-differential outcome misclassification. We assigned beta distributions to sensitivity and specificity and sampled from these 100 000 times for summary-level and 10 000 times for record-level PBA. Using these values, we simulated outcomes and applied IPTW logistic regression to adjust for confounding and misclassification. Sensitivity analyses excluded ICS + LABA + LAMA (triple therapy) users.

Results: Among 161 411 patients with COPD, ICS users had increased odds of COVID-19 hospitalisations and death compared with LABA/LAMA users (OR for COVID-19 hospitalisation 1.59 (95% CI 1.31-1.92); OR for COVID-19 death 1.63 (95% CI 1.26-2.11)). After IPTW and exclusion of people using triple therapy, ORs moved towards the null. All implementations of QBA, both record- and summary-level PBA, modestly shifted the ORs away from the null and increased uncertainty.

Conclusions: We observed increased risks of COVID-19 hospitalisation and death among ICS users compared to LABA/LAMA users. Outcome misclassification was unlikely to change the conclusions of the study, but confounding by indication remains a concern.

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使用定量偏倚分析校正COVID-19结局的错误分类：吸入皮质类固醇与COVID-19结局的应用实例

背景：在大流行期间，人们担心对COVID-19结局的不充分确定可能影响药物流行病学研究中治疗效果的估计。我们使用概率偏倚分析（PBA）评估了结果错误分类对第一次大流行期间英国吸入皮质类固醇（ICS）与COVID-19住院和死亡之间关联的影响。方法：使用临床实践研究数据链Aurum的数据，我们于2020年3月1日定义了一个慢性阻塞性肺疾病（COPD）队列。我们使用治疗加权逆概率（IPTW） logistic回归比较了ICS/长效β-激动剂（LABA）使用者和LABA/LAMA使用者的COVID-19住院和死亡风险。我们使用PBA来评估非差异结局错误分类的影响。我们将beta分布分配给灵敏度和特异性，并从这些样本中抽取10万次用于总结水平PBA， 10000次用于记录水平PBA。利用这些值，我们模拟了结果，并应用IPTW逻辑回归来调整混淆和误分类。敏感性分析排除了ICS + LABA + LAMA（三联疗法）使用者。结果：在16411例COPD患者中，ICS使用者与LABA/LAMA使用者相比，COVID-19住院和死亡的几率增加(COVID-19住院的OR为1.59 (95% CI 1.31-1.92)；COVID-19死亡的OR为1.63 （95% CI 1.26-2.11）。在IPTW和排除使用三联疗法的患者后，ORs趋于零。QBA的所有实现，包括记录级和摘要级PBA，都适度地将or从null移开，并增加了不确定性。结论：我们观察到ICS使用者与LABA/LAMA使用者相比，COVID-19住院和死亡的风险增加。结果的错误分类不太可能改变研究的结论，但适应症的混淆仍然是一个问题。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacoepidemiology and Drug Safety 医学-药学

CiteScore

4.80

自引率

7.70%

发文量

173

审稿时长

3 months

期刊介绍： The aim of Pharmacoepidemiology and Drug Safety is to provide an international forum for the communication and evaluation of data, methods and opinion in the discipline of pharmacoepidemiology. The Journal publishes peer-reviewed reports of original research, invited reviews and a variety of guest editorials and commentaries embracing scientific, medical, statistical, legal and economic aspects of pharmacoepidemiology and post-marketing surveillance of drug safety. Appropriate material in these categories may also be considered for publication as a Brief Report. Particular areas of interest include: design, analysis, results, and interpretation of studies looking at the benefit or safety of specific pharmaceuticals, biologics, or medical devices, including studies in pharmacovigilance, postmarketing surveillance, pharmacoeconomics, patient safety, molecular pharmacoepidemiology, or any other study within the broad field of pharmacoepidemiology; comparative effectiveness research relating to pharmaceuticals, biologics, and medical devices. Comparative effectiveness research is the generation and synthesis of evidence that compares the benefits and harms of alternative methods to prevent, diagnose, treat, and monitor a clinical condition, as these methods are truly used in the real world; methodologic contributions of relevance to pharmacoepidemiology, whether original contributions, reviews of existing methods, or tutorials for how to apply the methods of pharmacoepidemiology; assessments of harm versus benefit in drug therapy; patterns of drug utilization; relationships between pharmacoepidemiology and the formulation and interpretation of regulatory guidelines; evaluations of risk management plans and programmes relating to pharmaceuticals, biologics and medical devices.