Luce J M
Department of Medicine, University of California, San Francisco.
Crit Care Med. 1993 Aug;21(8):1233-41. doi: 10.1097/00003246-199308000-00026.
HA-1A, a monoclonal antibody against endotoxin, was thought to be effective in treating patients with Gram-negative sepsis. Because of this possibility, many clinicians felt obligated to use the drug and assumed that its product license application would be approved by the U.S. Food and Drug Administration (FDA). Nevertheless, the efficacy of HA-1A was not conclusively demonstrated by a first clinical trial. The FDA rejected the product license application and requested a second clinical trial, which was suspended after excess mortality was noted in patients treated with HA-1A. This review of the history of the drug was prepared to provide clinicians and sepsis investigators with information about HA-1A and, by extension, the process by which new technology is introduced into critical care practice.
Data used to prepare this review were obtained from the author's personal files as well as the computerized MEDLINE database.
Studies were selected for their relevance to the history of HA-1A and their relevance to the introduction of potentially useful medical technology.
The author extracted all applicable data.
Although the first clinical trial of HA-1A suggested that the drug was effective in treating patients with Gram-negative bacteremia with or without shock, further analysis by the FDA indicated a benefit only for bacteremic patients with shock. Furthermore, the original study design was not followed, leading in part to the FDA's refusal of the product license application. Concern also was raised over the issue of identifying which patients should receive HA-1A and the cost of the drug, which would have put it past the reach of some American hospitals and thereby, would have conflicted with the ethical principle of social justice. Finally, the second trial suggested that HA-1A might be harmful.
Due to the FDA's action, the issues raised about HA-1A, and the results of the two clinical trials, clinicians should not use the drug. The history of HA-1A provides insights about how new technology is and will be introduced into critical care practice.
HA-1A是一种抗内毒素单克隆抗体，曾被认为对治疗革兰氏阴性菌败血症患者有效。鉴于这种可能性，许多临床医生觉得有义务使用该药，并认为其产品许可申请会得到美国食品药品监督管理局（FDA）的批准。然而，首次临床试验并未确凿地证明HA-1A的疗效。FDA拒绝了该产品许可申请，并要求进行第二次临床试验，但在使用HA-1A治疗的患者中发现有过高死亡率后，第二次试验被暂停。撰写本药物历史回顾是为了向临床医生和败血症研究人员提供有关HA-1A的信息，并进而介绍将新技术引入重症监护实践的过程。
用于撰写本回顾的数据来自作者的个人文件以及计算机化的MEDLINE数据库。
选择的研究需与HA-1A的历史相关，以及与引入潜在有用的医疗技术相关。
作者提取了所有适用数据。
尽管HA-1A的首次临床试验表明该药对治疗伴有或不伴有休克的革兰氏阴性菌血症患者有效，但FDA的进一步分析表明仅对伴有休克的菌血症患者有益。此外，未遵循原始研究设计，这在一定程度上导致FDA拒绝该产品许可申请。对于确定哪些患者应接受HA-1A以及药物成本的问题也引发了关注，这会使一些美国医院无力承担，从而与社会正义的伦理原则相冲突。最后，第二次试验表明HA-1A可能有害。
鉴于FDA的行动、有关HA-1A提出的问题以及两项临床试验的结果，临床医生不应使用该药。HA-1A的历史为新技术如何以及将如何引入重症监护实践提供了见解。
