On the use of laboratory markers as surrogates for clinical endpoints in the evaluation of treatment for HIV infection.
On the use of laboratory markers as surrogates for clinical endpoints in the evaluation of treatment for HIV infection.
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关于使用实验室标志物作为临床终点的替代物来评估 HIV 感染的治疗。
DOI：
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发表时间：
1990
期刊：
影响因子：
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通讯作者：
Susan S. Ellenberg
中科院分区：
文献类型：
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作者：
S. G. Machado;Mitchell H. Gail;Susan S. Ellenberg
加快就人类免疫缺陷病毒(艾滋病毒)感染的新疗法的疗效作出决定是有强烈的伦理和实际理由的。一种策略是在评估新疗法时，使用疾病进展的早期标记物，如CD4+淋巴细胞水平，作为最终临床终点的替代品，如获得性免疫缺陷综合征(AIDS)的发展或死亡。我们使用了一个简单的三种健康状态之间的转换模型(很好；活着，但有不利的标志物；以及经历了一个明确的临床终点)来检查基于替代终点的治疗比较预测最终临床益处的程度。通过选择参数来模拟HIV感染的治疗，临床试验的计算机模拟表明，通过使用替代终点，可以节省大量时间。然而，如果治疗有延迟毒性或只有短暂的益处，依赖代用品会导致对最终临床益处的严重高估。同样，当治疗对从良好状态到标记物状态的转变没有影响，但确实降低了从标记物状态到最终临床终点和直接从良好状态到最终临床终点的转换率时，对替代物的依赖导致对最终临床益处的严重低估。
There are strong ethical and practical reasons for hastening decision-making about the efficacy of new treatments for human immunodeficiency virus (HIV) infection. One strategy is to use early markers of disease progression, such as CD4+ lymphocyte levels, as surrogates for ultimate clinical endpoints, such as the development of acquired immune deficiency syndrome (AIDS) or death, in the evaluation of new therapies. We used a simple model of transitions among three health states (well; alive but with an adverse marker; and having experienced a definitive clinical endpoint) to examine the extent to which treatment comparisons based on the surrogate endpoint predict ultimate clinical benefits. With parameters chosen to model the treatment of HIV infection, computer simulations of clinical trials demonstrated substantial time savings by use of the surrogate endpoint. However, reliance on the surrogate led to serious overestimates of ultimate clinical benefit if treatment entailed delayed toxicity or had only transient beneficial effects. Likewise, reliance on the surrogate led to serious underestimates of ultimate clinical benefit when the treatment had no effect on the transition from well to the marker state but did reduce the rates of transition from the marker state to the ultimate clinical endpoint and directly from the well state to the ultimate clinical endpoint.