Meinert Curtis L, Breitner John C S
Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD, USA.
Alzheimers Dement. 2008 Jan;4(1 Suppl 1):S7-S14. doi: 10.1016/j.jalz.2007.10.007. Epub 2007 Dec 21.
A randomized trial is a randomized trial. The basic ingredients do not change with different purposes whether for treatment or prevention of disease. Likewise, the problems and difficulties are mostly the same. But there are differences in approach and philosophy. Here we discuss problems in trials focused on healthy people to determine whether drugs can delay or prevent adverse health events, with the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT) as an example. An important difference separating treatment trials from prevention trials is the length of time needed to demonstrate a difference with treatment. Related to this is the risk-benefit calculus of the trial. Treatment trials are aimed at "curing" or ameliorating disease, for example, as with trials involving people with Alzheimer's disease (AD) dementia to determine whether treatment is useful in dealing with the AD-induced dementia. Like other treatment trials, those targeting AD dementia balance these benefits against the risks of treatment. But by contrast, benefit in prevention trials, if any, will be found only in the absence or delay in disease onset, often after years of continuous treatment. As in ADAPT, the separation in timing of risk versus benefit often brings difficult decisions about how long to continue the trial in the absence of any apparent benefit to treatment. Other difficulties similarly relate to the length of prevention trials. In hopes that some lessons learned from ADAPT will assist future prevention trials, especially in the elderly, we describe several conundrums and problems experienced in this trial and attempt when possible to extend our observations to the larger class of long-term drug prevention trials.
随机试验就是随机试验。无论目的是治疗还是预防疾病，其基本要素都不会因目的不同而改变。同样，问题和困难大多是相同的。但在方法和理念上存在差异。在此，我们以阿尔茨海默病抗炎预防试验（ADAPT）为例，讨论针对健康人群以确定药物是否能延缓或预防不良健康事件的试验中的问题。区分治疗试验和预防试验的一个重要差异在于证明治疗效果所需的时间长度。与此相关的是试验的风险效益计算。治疗试验旨在“治愈”或改善疾病，例如，涉及阿尔茨海默病（AD）痴呆患者的试验，以确定治疗对治疗AD所致痴呆是否有用。与其他治疗试验一样，针对AD痴呆的试验会在这些益处与治疗风险之间进行权衡。但相比之下，预防试验中的益处（如果有的话）只有在疾病未发生或发病延迟时才能发现，通常是在多年持续治疗之后。就像在ADAPT试验中一样，风险与益处的时间分离常常会带来关于在没有任何明显治疗益处的情况下试验要持续多久的艰难决策。其他困难同样与预防试验的时长有关。希望从ADAPT试验中学到的一些经验教训能帮助未来的预防试验，尤其是针对老年人的试验，我们描述了该试验中遇到的几个难题和问题，并尽可能将我们的观察结果推广到更广泛的长期药物预防试验类别中。
