Department of Global Health and Population, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.
Department of Epidemiology, Department of Immunology and Infectious Diseases, Center for Communicable Disease Dynamics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.
J Med Ethics. 2017 Sep;43(9):625-631. doi: 10.1136/medethics-2015-103220. Epub 2017 Apr 10.
During the 2014-2015 Ebola outbreak in Guinea, Liberia and Sierra Leone, many opposed the use of individually randomised controlled trials to test candidate Ebola vaccines. For a raging fatal disease, they explained, it is unethical to relegate some study participants to control arms. In Zika and future emerging infections, similar opposition may hinder urgent vaccine research, so it is best to address these questions now. This article lays out the ethical case for individually randomised control in testing vaccines against many emerging infections, including lethal infections in low-income countries, even when at no point in the trial do the controls receive the countermeasures being tested. When individual randomisation is feasible-and it often will be-it tends to save more lives than alternative designs would. And for emerging infections, individual randomisation also tends as such to improve care, access to the experimental vaccine and prospects for all participants relative to their opportunities absent the trial, and no less than alternative designs would. That obtains even under placebo control and without equipoise-requiring which would undermine individual randomisation and the alternative designs that opponents proffered. Our arguments expound four often-neglected factors: benefits to non-participants, benefits to participants once a trial is over including post-trial access to the study intervention, participants' prospects before randomisation to arms and the near-inevitable disparity between arms in any randomised controlled trial.
在 2014 年至 2015 年期间，埃博拉疫情在几内亚、利比里亚和塞拉利昂爆发，许多人反对使用个体随机对照试验来测试埃博拉候选疫苗。他们解释说，对于一种肆虐的致命疾病，将一些研究参与者置于对照组是不道德的。在寨卡病毒和未来的新发传染病中，类似的反对意见可能会阻碍紧急疫苗研究，因此最好现在就解决这些问题。本文阐述了针对许多新发传染病（包括低收入国家的致命传染病）测试疫苗时采用个体随机对照试验的伦理理由，即使在试验的任何阶段对照组都不会接受正在测试的对策。当个体随机化可行时——而且通常是可行的——它往往比其他设计方案能挽救更多生命。对于新发传染病，个体随机化也往往会改善护理、获得实验疫苗的机会以及相对于试验外的机会，使所有参与者的前景得到改善，而且不会低于其他设计方案。即使在安慰剂对照且没有均衡（这将破坏个体随机化和反对者提出的替代设计）的情况下也是如此。我们的论点阐述了四个经常被忽视的因素：非参与者的利益、试验结束后参与者的利益，包括试验后获得研究干预措施的机会、参与者在随机分组前进入试验组的前景，以及任何随机对照试验中手臂之间几乎不可避免的差异。
