Neaton J D, Wentworth D N, Rhame F, Hogan C, Abrams D I, Deyton L
Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis 55414.
Stat Med. 1994;13(19-20):2107-25. doi: 10.1002/sim.4780131919.
In most clinical trials of antiretroviral therapy for patients infected with HIV, the major outcome variable has been the combined clinical endpoint of any new or recurrent AIDS defining event. We review features of combined endpoints and use data from the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) to evaluate this outcome measure in terms of relevance, diagnostic certainty and sensitivity. We conclude that this endpoint is not relevant because: (i) the 19 different events constituting the combined endpoint are equally weighted in analyses even though they vary considerably in terms of risk of death; and (ii) events after the first are ignored, thus the event profile of patients is not taken into account in making treatment comparisons. We also conclude that power may be low with use of this endpoint if treatments under study do not have an immediate impact on disease progression, if some events which occur soon after randomization represent a disease process that has already begun to incubate, or if treatment differences for the various events constituting the combined endpoint are differentially effected by treatment. Since the ease and certainty of diagnosis of each of the 19 events also vary, we recommend that survival be the primary endpoint of antiretroviral trials, and that all opportunistic events experienced by patients, not just the first, be collected and summarized. Trial reports should include comparisons of incidence of each event by treatment group so that readers can rank events as they please. A single summary measure which considers severity and the entire event profile, as described here, would also be useful for assessing the impact of treatments on quality of life. Further research on approaches for weighting and combining multiple outcome measures is needed.
在大多数针对感染HIV患者的抗逆转录病毒疗法临床试验中，主要结局变量一直是任何新的或复发性艾滋病定义事件的综合临床终点。我们回顾了综合终点的特征，并使用艾滋病临床研究特里·贝恩社区项目（CPCRA）的数据，从相关性、诊断确定性和敏感性方面评估这一结局指标。我们得出结论，这个终点不相关，原因如下：（i）构成综合终点的19种不同事件在分析中被同等加权，尽管它们在死亡风险方面差异很大；（ii）首次事件之后的事件被忽略，因此在进行治疗比较时没有考虑患者的事件概况。我们还得出结论，如果所研究的治疗方法对疾病进展没有立即影响，如果随机分组后不久发生的一些事件代表已经开始潜伏的疾病过程，或者如果构成综合终点的各种事件的治疗差异受到治疗的不同影响，那么使用这个终点时检验效能可能较低。由于这19种事件中每种事件的诊断难易程度和确定性也各不相同，我们建议生存应作为抗逆转录病毒试验的主要终点，并且应收集和汇总患者经历的所有机会性事件，而不仅仅是首次事件。试验报告应包括按治疗组对每种事件发生率的比较，以便读者可以根据自己的意愿对事件进行排序。如本文所述，一种考虑严重程度和整个事件概况的单一汇总指标，对于评估治疗对生活质量的影响也将是有用的。需要对加权和合并多个结局指标的方法进行进一步研究。
