Inserm U897, Research Centre for Epidemiology and Biostatistics, Bordeaux, France.
Clin Trials. 2010 Feb;7(1):19-35. doi: 10.1177/1740774509356117.
In many fields, the choice of a primary endpoint for a trial is not always the ultimate clinical endpoint of interest, but rather some surrogate endpoint believed to be relevant for predicting the effect of the intervention on the clinical endpoint. The classic example of such a field is clinical HIV treatment research, where a variety of primary endpoints are used to evaluate the efficacy of new antiretroviral drugs or new combinations of existing drugs. The choice of endpoint reflects either the goal of therapy as recommended by treatment guidelines (e.g. rapid virological suppression) or the licensing requirements of official drug approval organizations (e.g. time to loss of virological response [TLOVR]).
To review the diversity of endpoints used in recent clinical trials in HIV infection and highlight the methodological issues.
We identified articles relating to antiretroviral therapy by searching PubMed and through hand searches of relevant conference abstracts. We restricted the search to randomized controlled trials conducted in HIV-infected adults published/presented from January 2005 until March 2008.
We identified 28 trials in antiretroviral-naive patients (i.e. patients who were starting antiretroviral therapy for the first time at the time of randomization) and 23 trials in antiretroviral-experienced patients. Most trials were performed for purposes of drug licensing, but others were focused on strategies of using approved drugs. Most trials (40 of 51) used a composite primary endpoint (TLOVR in 13). Of note, 22 of these 40 studies reported that they had used a purely virological efficacy endpoint, but the primary endpoint was actually a composite one due to the way in which missing data and treatment switches were considered as failures.
Examples are restricted to HIV clinical trials.
Whilst most current HIV clinical trials use composite primary endpoints, there are substantial differences in the components that make up these endpoints. In HIV and other fields where precise definitions are variable, guidelines for standardization of definition and reporting would greatly improve the ability to compare trial results.
在许多领域，试验的主要终点并不总是最终的临床关注终点，而是一些被认为与预测干预对临床终点影响相关的替代终点。这种情况的典型例子是临床 HIV 治疗研究，其中使用各种主要终点来评估新抗逆转录病毒药物或现有药物新组合的疗效。终点的选择反映了治疗指南推荐的治疗目标（例如快速病毒学抑制）或官方药物批准机构的许可要求（例如病毒学应答丧失时间 [TLOVR]）。
综述 HIV 感染近期临床试验中使用的终点多样性，并强调方法学问题。
我们通过在 PubMed 上搜索以及查阅相关会议摘要，确定了与抗逆转录病毒治疗相关的文章。我们将搜索范围限制为 2005 年 1 月至 2008 年 3 月发表/报告的在 HIV 感染成人中进行的随机对照试验。
我们确定了 28 项在初治患者（即在随机分组时首次开始接受抗逆转录病毒治疗的患者）中的试验和 23 项在经治患者中的试验。大多数试验是为了药物许可目的进行的，但也有一些侧重于使用已批准药物的策略。大多数试验（51 项中的 40 项）使用了复合主要终点（13 项中的 TLOVR）。值得注意的是，这 40 项研究中有 22 项报告说他们使用了纯粹的病毒学疗效终点，但由于缺失数据和治疗转换被视为失败的方式，主要终点实际上是复合终点。
示例仅限于 HIV 临床试验。
虽然目前大多数 HIV 临床试验使用复合主要终点，但这些终点的组成部分存在很大差异。在 HIV 和其他定义变量较大的领域，制定标准化定义和报告的指南将极大地提高比较试验结果的能力。
