Evaluating the Role of High-Dimensional Proxy Data in Confounding Adjustment in Multiple Sclerosis Research: A Case Study.

IF 2.4 4区医学 Q3 PHARMACOLOGY & PHARMACY

Pharmacoepidemiology and Drug Safety Pub Date : 2025-02-01 DOI:10.1002/pds.70112

Mohammad Ehsanul Karim, Md Belal Hossain, Huah Shin Ng, Feng Zhu, Hanna A Frank, Helen Tremlett

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Abstract

Purpose: Given the historical use of limited confounders in multiple sclerosis (MS) studies utilizing administrative health data, this brief report evaluates the impact of incorporating high-dimensional proxy information on confounder adjustment in MS research. We have implemented high-dimensional propensity score (hdPS) and high-dimensional disease risk score (hdDRS) methods to assess changes in effect estimates for the association between disease-modifying drugs (DMDs) and all-cause mortality in an MS cohort from British Columbia (BC), Canada.

Methods: We conducted a population-based retrospective study using linked administrative databases from BC, including health insurance registries, demographics, physician visits, hospitalizations, prescriptions, and vital statistics. The cohort comprised 19 360 individuals with MS, followed from January 1, 1996, to December 31, 2017. DMD exposure was defined as at least 180 days of use for beta-interferon or glatiramer acetate, or at least 90 days for other DMDs. The outcome was time to all-cause mortality. We compared Cox proportional hazards models adjusting for investigator-specified covariates with those incorporating additional empirical covariates using hdPS and hdDRS methods.

Results: In the unadjusted analysis, DMD exposure was associated with a 69% lower risk of mortality (HR 0.31; 95% CI: 0.27-0.36). Adjusting for investigator-specified covariates, the adjusted hazard ratio (aHR) was 0.76 (95% CI: 0.65-0.89). HdPS analyses showed a 20%-23% lower mortality risk (aHRs: 0.77 to 0.80), while hdDRS analyses indicated a 19%-21% reduction (aHRs: 0.79 to 0.81).

Conclusions: Incorporating high-dimensional proxy information resulted in minor variations in effect estimates compared to traditional covariate adjustment. These findings suggest that the impact of residual confounding in the question under consideration may be modest. Further research should explore additional data dimensions and replicate these findings across different datasets.

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评估高维代理数据在多发性硬化症混杂校正研究中的作用：一个案例研究。

目的：考虑到在利用行政健康数据的多发性硬化症（MS）研究中有限混杂因素的历史使用，本简短报告评估了在MS研究中纳入高维代理信息对混杂因素调整的影响。我们实施了高维倾向评分（hdPS）和高维疾病风险评分（hdDRS）方法，以评估来自加拿大不列颠哥伦比亚省（BC）的MS队列中疾病改善药物（dmd）与全因死亡率之间关联的效应估计的变化。方法：我们使用不列颠哥伦比亚省相关的管理数据库进行了一项基于人群的回顾性研究，包括健康保险登记、人口统计、医生就诊、住院、处方和生命统计数据。该队列包括19360名MS患者，随访时间为1996年1月1日至2017年12月31日。DMD暴露定义为使用干扰素或醋酸格拉替默至少180天，或使用其他DMD至少90天。结果是全因死亡率。我们比较了采用hdPS和hdDRS方法调整研究者指定协变量的Cox比例风险模型与那些纳入额外经验协变量的Cox比例风险模型。结果：在未经调整的分析中，DMD暴露与死亡风险降低69%相关(HR 0.31；95% ci: 0.27-0.36)。调整研究者指定的协变量后，调整后的风险比（aHR）为0.76 （95% CI: 0.65-0.89）。HdPS分析显示死亡率降低20%-23% (ahr: 0.77 - 0.80)，而hdDRS分析显示死亡率降低19%-21% （ahr: 0.79 - 0.81）。结论：与传统的协变量调整相比，纳入高维代理信息导致效果估计的变化较小。这些发现表明，在考虑的问题中，残留混淆的影响可能是适度的。进一步的研究应该探索更多的数据维度，并在不同的数据集上复制这些发现。

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.