Comparison of a Target Trial Emulation Framework vs Cox Regression to Estimate the Association of Corticosteroids With COVID-19 Mortality.
Comparison of a Target Trial Emulation Framework vs Cox Regression to Estimate the Association of Corticosteroids With COVID-19 Mortality.
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DOI：
10.1001/jamanetworkopen.2022.34425
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发表时间：
2022-10-03
影响因子：
13.8
通讯作者：
Diaz, Ivan
中科院分区：
文献类型：
--
作者：
Hoffman, Katherine L.;Schenck, Edward J.;Satlin, Michael J.;Whalen, William;Pan, Di;Williams, Nicholas;Diaz, Ivan
在估计皮质类固醇与中重度COVID-19患者死亡率的相关性时，现代统计推断方法与临床文献中常见的方法相比如何？在一项使用3298名住院COVID-19患者的回顾性数据的队列研究中，使用双重稳健估计程序的目标试验模拟成功地从随机临床试验的荟萃分析中恢复了基准。相比之下，临床研究文献中常见的分析方法通常无法恢复基准。这些发现表明，基于观察数据的临床研究可以用于估计与随机临床试验相似的结果;然而，这些估计的正确性需要根据与临床研究现行标准不同的原则设计和分析数据集。这项队列研究比较了使用观察数据进行统计推断的方法，以复制随机临床试验荟萃分析的结果。现代研究设计和分析技术的交流和采用对于从观察数据中改进临床研究非常重要。比较现代统计推断方法（包括目标试验仿真框架和双重稳健估计）与临床文献中常见的方法（如考克斯比例风险模型）。这项回顾性队列研究使用纵向电子健康记录数据来评估纽约、纽约多中心医院系统住院后28天的结局。参与者包括2020年3月1日至5月15日期间住院的成年患者，他们患有COVID-19，并且没有长期使用皮质类固醇。数据分析时间为2021年10月至2022年3月。皮质类固醇暴露定义为24小时内超过0.5 mg/kg甲基强的松龙当量。对于靶向试验模拟，如果患者符合重度缺氧与无皮质类固醇的标准，则暴露皮质类固醇6天。对于临床文献中常见的方法，考克斯回归模型中用于变量的治疗定义因研究设计而异（无时间范围、重度缺氧后1天和5天）。主要结局是从住院开始的28天死亡率。使用世界卫生组织（WHO）对皮质类固醇随机临床试验的荟萃分析作为基准，评估了皮质类固醇与中重度COVID-19患者死亡率的相关性。共评估了3298例患者（中位[IQR]年龄，65 [53 - 77]岁; 1970例[60%]男性），包括423例在住院期间任何时间点接受皮质类固醇的患者和699例在住院后28天内死亡的患者。靶试验模拟分析发现，皮质类固醇与28天死亡率降低相关，从32.2%（95% CI，30.9%-33.5%）降至25.7%（95% CI，24.5%-26.9%）。该估计值与WHO荟萃分析比值比0.66（95% CI，0.53 - 0.82）在性质上相同。使用与当前皮质类固醇研究方法相当的方法，风险比的大小和方向范围为0.50（95%CI，0.41 - 0.62）至1.08（95%CI，0.80 - 1.47）。这些结果表明，基于观察数据的临床研究可以用于估计与随机临床试验相似的结果;然而，这些估计的正确性需要根据与临床研究现行标准不同的原则设计研究和分析数据。
How do modern methods for statistical inference compare with approaches common in the clinical literature when estimating the association of corticosteroids with mortality for patients with moderate to severe COVID-19? In a cohort study using retrospective data for 3298 hospitalized patients with COVID-19, target trial emulation using a doubly robust estimation procedure successfully recovers a benchmark from a meta-analysis of randomized clinical trials . In contrast, analytic approaches common in the clinical research literature generally cannot recover the benchmark. These findings suggest that clinical research based on observational data can be used to estimate findings similar to those from randomized clinical trials; however, the correctness of these estimates requires designing and analyzing the data set on principles that are different from the current standard in clinical research. This cohort study compares methods for statistical inference using observational data in replicating findings from a meta-analysis of randomized clinical trials. Communication and adoption of modern study design and analytical techniques is of high importance for the improvement of clinical research from observational data. To compare a modern method for statistical inference, including a target trial emulation framework and doubly robust estimation, with approaches common in the clinical literature, such as Cox proportional hazards models. This retrospective cohort study used longitudinal electronic health record data for outcomes at 28-days from time of hospitalization within a multicenter New York, New York, hospital system. Participants included adult patients hospitalized between March 1 and May 15, 2020, with COVID-19 and not receiving corticosteroids for chronic use. Data were analyzed from October 2021 to March 2022. Corticosteroid exposure was defined as more than 0.5 mg/kg methylprednisolone equivalent in a 24-hour period. For target trial emulation, exposures were corticosteroids for 6 days if and when a patient met criteria for severe hypoxia vs no corticosteroids. For approaches common in clinical literature, treatment definitions used for variables in Cox regression models varied by study design (no time frame, 1 day, and 5 days from time of severe hypoxia). The main outcome was 28-day mortality from time of hospitalization. The association of corticosteroids with mortality for patients with moderate to severe COVID-19 was assessed using the World Health Organization (WHO) meta-analysis of corticosteroid randomized clinical trials as a benchmark. A total of 3298 patients (median [IQR] age, 65 [53-77] years; 1970 [60%] men) were assessed, including 423 patients who received corticosteroids at any point during hospitalization and 699 patients who died within 28 days of hospitalization. Target trial emulation analysis found corticosteroids were associated with a reduced 28-day mortality rate, from 32.2%; (95% CI, 30.9%-33.5%) to 25.7% (95% CI, 24.5%-26.9%). This estimate is qualitatively identical to the WHO meta-analysis odds ratio of 0.66 (95% CI, 0.53-0.82). Hazard ratios using methods comparable with current corticosteroid research range in size and direction, from 0.50 (95% CI, 0.41-0.62) to 1.08 (95% CI, 0.80-1.47). These findings suggest that clinical research based on observational data can be used to estimate findings similar to those from randomized clinical trials; however, the correctness of these estimates requires designing the study and analyzing the data based on principles that are different from the current standard in clinical research.
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影响因子：
2.7
作者：
Gerds, TA;Schumacher, M
通讯作者：
Schumacher, M
DOI：
10.1016/j.cmi.2020.09.014
发表时间：
2021-01
期刊：
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
影响因子：
--
作者：
Bartoletti M;Marconi L;Scudeller L;Pancaldi L;Tedeschi S;Giannella M;Rinaldi M;Bussini L;Valentini I;Ferravante AF;Potalivo A;Marchionni E;Fornaro G;Pascale R;Pasquini Z;Puoti M;Merli M;Barchiesi F;Volpato F;Rubin A;Saracino A;Tonetti T;Gaibani P;Ranieri VM;Viale P;Cristini F;PREDICO Study Group
通讯作者：
PREDICO Study Group
影响因子：
5
作者：
Hernan, Miguel A.;Robins, James M.
通讯作者：
Robins, James M.
用于事件时间数据的参数G形式：直觉和有效的示例。
DOI：
10.1097/ede.0000000000000160
发表时间：
2014-11
期刊：
Epidemiology (Cambridge, Mass.)
影响因子：
--
作者：
Keil AP;Edwards JK;Richardson DB;Naimi AI;Cole SR
通讯作者：
Cole SR
DOI：
10.1183/13993003.02808-2020
发表时间：
2020-12
期刊：
The European respiratory journal
影响因子：
--
作者：
Edalatifard M;Akhtari M;Salehi M;Naderi Z;Jamshidi A;Mostafaei S;Najafizadeh SR;Farhadi E;Jalili N;Esfahani M;Rahimi B;Kazemzadeh H;Mahmoodi Aliabadi M;Ghazanfari T;Sattarian M;Ebrahimi Louyeh H;Raeeskarami SR;Jamalimoghadamsiahkali S;Khajavirad N;Mahmoudi M;Rostamian A
通讯作者：
Rostamian A