Virologic and regimen termination surrogate end points in AIDS clinical trials
Virologic and regimen termination surrogate end points in AIDS clinical trials
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DOI：
10.1001/jama.285.6.777
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发表时间：
2001-02-14
影响因子：
120.7
通讯作者：
Kuritzkes, DR
中科院分区：
文献类型：
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作者：
Gilbert, PB;DeGruttola, V;Kuritzkes, DR
抑制血浆人类免疫缺陷病毒(HIV)RNA水平已被广泛接受为HIV疾病进展的合适替代终点，目前在许多抗逆转录病毒试验中被用作确定疗效的主要终点。然而，这一终点并不总是衡量治疗的其他重要影响，如诱导多药耐药，这耗尽了未来的治疗选择，以及毒性影响。一种直接影响这些治疗成本的替代方案是复合方案终止终点，其定义为由于病毒学失败或与治疗相关的毒性效应而对方案进行的方案决定的改变。讨论了使用纯病毒学与各种复合初级终点的利弊。结论包括(1)试验的临床目标指导主要终点的选择，(2)纯病毒学终点通常是可取的，(3)在解释研究结果时分析两种终点类型可能很重要，以及(4)需要进行长期临床结果研究以确定最具预测性的替代终点。
Suppression of plasma human immunodeficiency virus (HIV) RNA levels has been widely accepted as an appropriate surrogate end point for HIV disease progression, and it is currently used as the primary end point to determine efficacy in many antiretroviral trials. However, this end point does not always measure other important effects of treatment, such as inducement of multidrug resistance, which depletes future therapy options, and toxic effects. An alternative that directly factors in these treatment costs is a composite regimen termination end point, defined as a protocol-determined change in regimen due to either virologic failure or treatment-related toxic effects. Pros and cons for using purely virologic vs various composite primary end points are discussed. Conclusions include (1) a trial's clinical objective guides the choice of primary end point, (2) a purely virologic end point is often preferable, (3) it may be important to analyze both end point types in interpreting study results, and (4) long-term clinical outcome studies are needed for identifying the most predictive surrogate end points.