Flaherty M L, Karlawish J, Khoury J C, Kleindorfer D, Woo D, Broderick J P
Department of Neurology, University of Cincinnati Academic Health Center, 260 Stetson St., Room 2316, Cincinnati, OH 45267-0525, USA.
Neurology. 2008 Nov 11;71(20):1566-71. doi: 10.1212/01.wnl.0000316196.63704.f5. Epub 2008 Aug 27.
Patients with stroke may have cognitive deficits that impact their capacity to provide informed consent for research. Some institutional review boards restrict surrogate consent to persons who have specific legal authority to provide it. We examined the importance of surrogate consent in the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Trial, the study that led to the only US Food and Drug Administration-approved treatment for acute ischemic stroke.
The NINDS rt-PA Stroke Trial randomized subjects with ischemic stroke to treatment with recombinant tissue plasminogen activator (rt-PA) or placebo. We compared the baseline characteristics and clinical outcomes of subjects enrolled by self-consent with those of subjects enrolled by surrogate consent.
Surrogate consent was used to enroll 439 of 624 (70%) subjects. Subjects enrolled by surrogate consent were older (68.5 vs 63.4 years, p < 0.001), had more severe strokes (median NIH Stroke Scale score 17 vs 9, p < 0.001), and were less likely to make a good recovery (p < 0.001 for all measures) than patients who provided their own consent. There was no interaction between method of consent and response to rt-PA. If the trial had used the same sample size and recruited at the same rate but excluded patients who could not provide their own consent, it would have taken 12.5 years to complete.
The National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator (rt-PA) Stroke Trial would not have been completed in a timely fashion without subjects enrolled by surrogate consent. Furthermore, exclusion of subjects who could not provide their own consent would have severely limited the generalizability and value of trial results.
中风患者可能存在认知缺陷，这会影响他们为研究提供知情同意的能力。一些机构审查委员会将替代同意限制在具有特定法律授权的人员范围内。我们在国立神经疾病与中风研究所（NINDS）的rt-PA中风试验中研究了替代同意的重要性，该试验促成了美国食品药品监督管理局唯一批准的急性缺血性中风治疗方法。
NINDS rt-PA中风试验将缺血性中风患者随机分为接受重组组织型纤溶酶原激活剂（rt-PA）治疗或安慰剂治疗两组。我们比较了通过自主同意入组的受试者与通过替代同意入组的受试者的基线特征和临床结局。
624名受试者中有439名（70%）通过替代同意入组。通过替代同意入组的受试者年龄更大（68.5岁对63.4岁，p<0.001），中风更严重（美国国立卫生研究院中风量表中位数评分17对9，p<0.001），与自主同意的患者相比，康复良好的可能性更小（所有指标p<0.001）。同意方式与对rt-PA的反应之间没有相互作用。如果试验采用相同的样本量并以相同的速率招募，但排除无法自主同意的患者，那么完成试验需要12.5年。
如果没有通过替代同意入组的受试者，国立神经疾病与中风研究所重组组织型纤溶酶原激活剂（rt-PA）中风试验就无法及时完成。此外，排除无法自主同意的受试者将严重限制试验结果的普遍性和价值。
