Introduction: Obtaining informed consent from acute ischemic stroke patients poses many challenges, especially in the context of a research setting. Specifically, consenting for alternative acute ischemic stroke treatments to the standard of care, Tissue Plasminogen Activator (tPA), can cause delays leading to increased time to reperfusion and worse outcomes. Objectives: We sought to investigate the experiences of researchers in existing active-control trials in acute ischemic stroke comparing investigational therapy to tPA in order to identify the approaches and challenges in obtaining informed consent in this unique patient population. Methods: Out of 401 articles evaluated, 14 trials met inclusion criteria of patients receiving IV tPA vs alternative treatment within 4.5 hours of onset of symptoms for acute ischemic stroke. Trial representatives were emailed by the study team with a request for a copy of their patient consent form, other documents related to informed consent, and to complete a survey concerning aspects of the consent process. Results: Of the 6 trials conducted across 6 continents that completed the survey in its entirety, 2 were ongoing, 4 were published between 2009 and 2016, and the median NIHSS for each published trial was at least an 8. All published trials in the sample stated that informed consent was obtained, but only half reported involvement of a research ethics committee. Although 3 trials performed in Europe or Asia reported directly consenting 75-100% of enrolled patients, the median NIHSS for these trials represented a moderate stroke. Trials with 75-100% of patients directly consented had shorter door to treatment (DTT) times than trials that directly consented less than 50% of enrolled patients. 5 trials allowed consent by proxy, but only 2 of those trials also required patient assent. 4 trials had translators available and translated consent documents, and these trials had longer DTT times. All trials relied on experienced providers or dedicated research coordinators to obtain informed consent; however, only 2 of 6 trials mentioned specific training with regards to informed consent skills. Conclusions: The current informed consent process is not transparent and poses challenges to investigators in the USA directly comparing tPA to an alternative treatment. International differences in the standards of informed consent, such as deferred consent, may have allowed more patients with moderate strokes to provide direct consent after treatment administration without delaying DTT time. While targeted and innovative approaches for informed consent are needed to improve patient outcomes, we must balance protecting the autonomy of individuals whose willing involvement enables such pivotal discoveries. The stroke community must aim for efficiency, transparency, and inclusion of patients of diverse backgrounds in the informed consent process so that therapeutic advances are possible.

中文翻译：

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国际临床试验中急性缺血性卒中的知情同意过程中的伦理考虑

简介：获得急性缺血性中风患者的知情同意构成许多挑战，尤其是在研究环境中。具体来说，同意采用替代标准的急性缺血性脑卒中治疗方法，即组织纤溶酶原激活物（tPA），可能会导致延误，导致再灌注时间延长和结果恶化。目的：我们试图研究研究人员在急性缺血性卒中的现有主动对照试验中的经验，并与tPA进行比较，以便确定在这种独特的患者群体中获得知情同意的方法和挑战。方法：在评估的401篇文章中，有14项试验符合在急性缺血性卒中症状发作后4.5小时内接受IV tPA与替代治疗的患者的纳入标准。研究团队通过电子邮件向试验代表发送了一份请求，要求其提供患者同意书的副本，与知情同意有关的其他文件，并完成有关同意过程各方面的调查。结果：在6个大洲进行的6项试验全部完成了调查，其中2项正在进行中，4项在2009年至2016年之间发表，每项公开试验的NIHSS中位数至少为8例。指出获得了知情同意，但是只有一半的人报告说有研究伦理委员会的参与。尽管在欧洲或亚洲进行的3项试验报告了直接同意的入组患者为75-100％，但这些试验的中位NIHSS代表中度卒中。与直接同意纳入研究的患者少于50％的试验相比，直接同意接受治疗的患者中有75-100％的试验的门诊时间（DTT）短。5项试验允许代理人同意，但其中只有2项试验还需要患者同意。4个试验有翻译员可用并翻译了同意书，并且这些试验的DTT时间更长。所有试验均依赖经验丰富的提供者或专门的研究协调员来获得知情同意；但是，在6项试验中，只有2项提到了有关知情同意技巧的专门培训。结论：当前的知情同意程序并不透明，并且直接将tPA与替代疗法进行比较给美国的研究人员带来了挑战。知情同意标准的国际差异，例如延期同意，可能允许更多中度卒中患者在治疗后获得直接同意，而不会延迟DTT时间。虽然需要有针对性的创新方法来获得知情同意，以改善患者的治疗效果，但我们必须权衡保护愿意参与这些关键发现的个人的自主权。中风社区必须致力于在知情同意过程中提高效率，透明度并将不同背景的患者纳入其中，以便有可能进行治疗。