Powers John H, Das Anita F, De Anda Carisa, Prokocimer Philippe
George Washington University School of Medicine, Washington, DC, USA.
InClin, San Mateo, CA, USA.
Contemp Clin Trials. 2016 Sep;50:265-72. doi: 10.1016/j.cct.2016.08.010. Epub 2016 Aug 13.
Outcome assessments as clinical trial endpoints should be well-defined, reliable, and reflect meaningful treatment benefits. For acute bacterial skin and skin structure infections (ABSSSI) trials, recent recommendations suggest a primary endpoint of reduction in skin lesion area. Objectives were: evaluate ABSSSI lesion area measurement reliability, evaluate impact of various lesion area definitions on treatment effect size, and explore relationships between lesion area and pain.
Data from two randomized, double-blinded Phase 3 trials comparing tedizolid to linezolid in ABSSSI and one open-label, non-comparative Phase 2 study of tedizolid in cellulitis/erysipelas and skin abscess were analyzed. Repeated lesion area measurements were prospectively obtained in all studies. In the open-label study, lesion area was measured by two investigators, using four different definitions. Repeated pain assessments using two patient-reported outcome instruments (Visual Analog Scale [VAS] and Faces Rating Scale [FRS]) were elicited in the randomized trials.
At baseline, lesion size did not correlate with pain intensity: r=0.02 for VAS and r<0.01 for FRS pain scores. However, decreasing lesion size and decreasing pain were strongly associated over time, regardless of initial lesion size or pain intensity (r=0.20 for VAS and r=0.21 for FRS scores at Day 10-13). Each lesion area definition demonstrated high inter-observer reliability (intra-class correlation coefficient>0.95).
Decreasing lesion area (indirect clinician-reported measure of benefit) and pain (direct patient-reported measure of benefit) were strongly associated over time, and lesion area measurements were reliable, regardless of their definition. These findings support both measures as outcome assessments in ABSSSI clinical trials.
Clinicaltrials.govNCT01519778, NCT01170221, and NCT01421511.
作为临床试验终点的结果评估应定义明确、可靠，并能反映有意义的治疗益处。对于急性细菌性皮肤和皮肤结构感染（ABSSSI）试验，近期建议将皮肤病变面积缩小作为主要终点。目标是：评估ABSSSI病变面积测量的可靠性，评估各种病变面积定义对治疗效应大小的影响，并探讨病变面积与疼痛之间的关系。
分析了两项在ABSSSI中将替加环素与利奈唑胺进行比较的随机、双盲3期试验，以及一项替加环素治疗蜂窝织炎/丹毒和皮肤脓肿的开放标签、非对照2期研究的数据。在所有研究中均前瞻性地获取了重复的病变面积测量值。在开放标签研究中，由两名研究人员使用四种不同的定义测量病变面积。在随机试验中，使用两种患者报告结局工具（视觉模拟量表[VAS]和面部表情评分量表[FRS]）进行重复的疼痛评估。
在基线时，病变大小与疼痛强度不相关：VAS评分为r = 0.02，FRS疼痛评分为r < 0.01。然而，随着时间的推移，无论初始病变大小或疼痛强度如何，病变大小的减小与疼痛的减轻都密切相关（第10 - 13天VAS评分为r = 0.20，FRS评分为r = 0.21）。每种病变面积定义均显示出较高的观察者间可靠性（组内相关系数>0.95）。
随着时间的推移，病变面积的减小（临床医生间接报告的益处衡量指标）与疼痛（患者直接报告的益处衡量指标）密切相关，并且病变面积测量是可靠的，无论其定义如何。这些发现支持将这两种测量方法作为ABSSSI临床试验中的结果评估指标。
Clinicaltrials.govNCT01519778、NCT01170221和NCT01421511。
Zotero 插件