Introduction of new technology into critical care practice

Objectives 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 Sources Data used to prepare this review were obtained from the author's personal files as well as the computerized MEDLINE database. Study Selection Studies were selected for their relevance to the history of HA-1A and their relevance to the introduction of potentially useful medical technology. Data Extraction The author extracted all applicable data. Data Synthesis 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. Conclusions Due to the FDA's action, the issues raised about HA-1A, and the results of the two clincial 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.(Crit Care Med 1993; 21:1233–1241)