Choosing an Index Date for Untreated Patients in External Comparator Studies.

IF 3.8 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Luis Antunes, Gerd Rippin, Eleanor Ralphs, Artis Luguzis, Kellyn Arnold, Hopin Lee
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引用次数: 0

Abstract

Background and objective: Selecting an index date (also called time zero or baseline) can be challenging for External Comparator (EC) studies when comparing against untreated patients. Existing literature addresses methods for defining an index date for untreated patients in observational studies generally, but not for EC studies specifically, which are likely to benefit from customized approaches.

Methods: A simulation study was performed to assess different index date assignments and analytical approaches in terms of bias and other performance characteristics: The first approach took the time from a major clinical event (say, diagnosis date) to treatment start as observed in the treated cohort and randomly assigned these times to the untreated cohort to derive the index dates. This approach was applied without and with the condition that the emulated index dates in the untreated cohort needed to be before the observed event times (index date emulation [IDE] and modified index date emulation approach [mIDE]). The second approach was to start the follow-up period at the diagnosis date (early index date approach [EID]) and to perform an analysis according to a time-dependent Cox model (or its generalization, e.g., a Marginal Structural Cox Model). This model was applied both in a traditional but also in a modified manner (modified early index date approach, mEID), where the modified model coded the treatment cohorts before the true (treated patients) and emulated (untreated patients, using IDE) treatment start dates to belong to a third treatment category. This allowed the treatment comparison of interest to be restricted to the time after the true and emulated treatment start dates.

Results: The IDE and mEID approaches were shown to be unbiased with identical performance, while mIDE and EID exhibited significant bias.

Conclusions: We showed that our EC analysis approach based on emulated index dates for untreated patients constitutes a valid concept, which may be advantageous for many external comparator studies.

在外部比较研究中选择未治疗患者的索引日期。
背景和目的:当与未治疗的患者进行比较时,外部比较器(EC)研究选择索引日期(也称为时间零或基线)可能具有挑战性。现有文献讨论了在观察性研究中为未治疗患者定义索引日期的方法,但没有专门针对EC研究,这可能受益于定制方法。方法:进行模拟研究,以评估不同的索引日期分配和分析方法的偏差和其他性能特征:第一种方法从治疗队列中观察到的主要临床事件(例如,诊断日期)到治疗开始的时间,并将这些时间随机分配给未治疗队列,以得出索引日期。该方法的应用没有且有一个条件,即未处理队列中的模拟索引日期需要在观察到的事件时间之前(索引日期模拟[IDE]和修改的索引日期模拟方法[mIDE])。第二种方法是在诊断日期开始随访(早期索引日期法[EID]),并根据时间相关的Cox模型(或其推广,例如边际结构Cox模型)进行分析。该模型既以传统方式应用,也以修改后的方式(修改的早期索引日期方法,mEID)应用,其中修改后的模型在真实(治疗患者)和模拟(未经治疗的患者,使用IDE)治疗开始日期之前编码治疗队列,属于第三种治疗类别。这允许将感兴趣的治疗比较限制在真实和模拟治疗开始日期之后的时间。结果:IDE和mEID方法表现出相同的无偏性,而mIDE和EID表现出显著的偏倚。结论:我们表明,基于未治疗患者的模拟索引日期的EC分析方法是一个有效的概念,这可能有利于许多外部比较研究。
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
Drug Safety
Drug Safety 医学-毒理学
CiteScore
7.60
自引率
7.10%
发文量
112
审稿时长
6-12 weeks
期刊介绍: Drug Safety is the official journal of the International Society of Pharmacovigilance. The journal includes: Overviews of contentious or emerging issues. Comprehensive narrative reviews that provide an authoritative source of information on epidemiology, clinical features, prevention and management of adverse effects of individual drugs and drug classes. In-depth benefit-risk assessment of adverse effect and efficacy data for a drug in a defined therapeutic area. Systematic reviews (with or without meta-analyses) that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement. Original research articles reporting the results of well-designed studies in disciplines such as pharmacoepidemiology, pharmacovigilance, pharmacology and toxicology, and pharmacogenomics. Editorials and commentaries on topical issues. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in Drug Safety Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.
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