Linden P K, Angus D C, Chelluri L, Branch R A
Department of Anesthesiology, University of Pittsburgh Medical Center, PA, USA.
J Crit Care. 1995 Dec;10(4):154-64. doi: 10.1016/0883-9441(95)90007-1.
This study was performed to compare the effect of entry criteria, patient population, and study design on outcome and projected cost-effectiveness of human anti-endotoxin antibody (HA-1A).
Patients with suspected or documented gram-negative bacteremia (GNB) with sepsis syndrome or shock received HA-1A during an open-label protocol. The patient characteristics and outcome measures of this series were compared with those of a placebo-controlled randomized clinical trial (RCT) of HA-1A. Both data sets were subjected to three published cost-effectiveness models of anti-endotoxin therapy, which were derived from RCT data.
One hundred thirty-one patients (43 with gram-negative bacteremia) received HA-1A during a 19-month open-label protocol. Comparison with the RCT results demonstrated greater severity of illness and higher 28-day mortality in the open-label protocol. When projected for open-label recipients, HA-1A was considerably less cost-effective than in the original projections based on RCT-derived data. This reduction in cost-effectiveness was consistent across all three models and their respective sensitivity analyses.
Extrapolating cost-effectiveness from RCT-derived analyses to open-label usage may yield widely inaccurate projections because of only small differences in patient population and the drug administration protocol.
本研究旨在比较入选标准、患者群体和研究设计对人抗内毒素抗体（HA-1A）的疗效及预期成本效益的影响。
患有疑似或确诊革兰氏阴性菌血症（GNB）并伴有脓毒症综合征或休克的患者在开放标签方案期间接受HA-1A治疗。将该系列患者的特征和结局指标与HA-1A的一项安慰剂对照随机临床试验（RCT）的结果进行比较。这两组数据集均采用了三种已发表的抗内毒素治疗成本效益模型，这些模型源自RCT数据。
在一项为期19个月的开放标签方案期间，131例患者（43例患有革兰氏阴性菌血症）接受了HA-1A治疗。与RCT结果比较显示，开放标签方案中的疾病严重程度更高，28天死亡率更高。当对开放标签方案的接受者进行预测时，HA-1A的成本效益比基于RCT数据的原始预测结果要低得多。成本效益的这种降低在所有三种模型及其各自的敏感性分析中都是一致的。
由于患者群体和给药方案仅有微小差异，将基于RCT分析得出的成本效益外推至开放标签使用可能会产生非常不准确的预测。
