Lodise Thomas P, Anzueto Antonio R, Weber David J, Shorr Andrew F, Yang Min, Smith Alexander, Zhao Qi, Huang Xingyue, File Thomas M
Albany College of Pharmacy and Health Sciences, Albany, New York, USA
University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Antimicrob Agents Chemother. 2015 Feb;59(2):1119-26. doi: 10.1128/AAC.03643-14. Epub 2014 Dec 8.
The primary driver of health care costs for patients with community-acquired pneumonia (CAP) is the hospital length of stay (LOS). Unfortunately, hospital LOS comparisons are difficult to make from phase III CAP trials because of their structured designs and prespecified treatment durations. However, an opportunity still exists to draw inferences about potential LOS differences between treatments through the use of surrogates for hospital discharge. The intent of this study was to quantify the time to a clinical response, a proxy for the time to discharge readiness, among hospitalized CAP patients who received either ceftaroline or ceftriaxone in two phase III CAP FOCUS clinical trials. On the basis of the Infectious Diseases Society of America and American Thoracic Society CAP management guidelines and recent FDA guidance documents for community-acquired bacterial pneumonia, a post hoc adjudication algorithm was constructed a priori to compare the time to a clinical response, a proxy for the time to discharge readiness, between patients who received ceftaroline or ceftriaxone. Overall, 1,116 patients (ceftaroline, n=562; ceftriaxone, n=554) from the pooled FOCUS trials met the selection criteria for this analysis. Kaplan-Meier analyses showed that ceftaroline was associated with a shorter time, measured in days, to meeting the clinical response criteria (P=0.03). Of the patients on ceftaroline, 61.0, 76.1, and 83.6% achieved a clinical response by days 3, 4, and 5, compared to 54.3, 69.8, and 79.3% of the ceftriaxone-treated patients. In the Cox regression, ceftaroline was associated with a shorter time to a clinical response (HR, 1.16, P=0.02). The methodology employed here provides a framework to draw comparative effectiveness inferences from phase III CAP efficacy trials. (The FOCUS trials whose data were analyzed in this study have been registered at ClinicalTrials.gov under registration no. NCT00621504 and NCT00509106.).
社区获得性肺炎（CAP）患者医疗费用的主要驱动因素是住院时间（LOS）。遗憾的是，由于III期CAP试验的结构化设计和预先确定的治疗持续时间，很难对住院时间进行比较。然而，通过使用出院替代指标，仍有机会推断不同治疗方法之间潜在的住院时间差异。本研究的目的是在两项III期CAP FOCUS临床试验中，对接受头孢洛林或头孢曲松治疗的住院CAP患者达到临床反应的时间进行量化，这是出院准备时间的一个替代指标。根据美国传染病学会和美国胸科学会的CAP管理指南以及美国食品药品监督管理局（FDA）最近关于社区获得性细菌性肺炎的指导文件，预先构建了一种事后判定算法，以比较接受头孢洛林或头孢曲松治疗的患者达到临床反应的时间，这是出院准备时间的一个替代指标。总体而言，来自汇总的FOCUS试验的1116例患者（头孢洛林组，n = 562；头孢曲松组，n = 554）符合本分析的入选标准。Kaplan-Meier分析表明，以天数衡量，头孢洛林与达到临床反应标准的时间较短相关（P = 0.03）。接受头孢洛林治疗的患者中，分别有61.0%、76.1%和83.6%在第3天、第4天和第5天达到临床反应，而接受头孢曲松治疗的患者这一比例分别为54.3%、69.8%和79.3%。在Cox回归分析中，头孢洛林与达到临床反应的时间较短相关（风险比，1.16；P = 0.02）。这里采用的方法提供了一个框架，以便从III期CAP疗效试验中得出比较有效性的推论。（本研究中分析其数据的FOCUS试验已在ClinicalTrials.gov上注册，注册号为NCT00621504和NCT00509106。）
