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How important is surrogate consent for stroke research?

From the Department of Neurology (M.L.F., D.K., D.W., J.P.B.), University of Cincinnati Academic Health Center, OH; Center for Epidemiology and Biostatistics (J.C.K.), Cincinnati Children’s Hospital Medical Center, OH; and Department of Medicine (J.K.), University of Pennsylvania, Philadelphia, PA.

Address correspondence and reprint requests to Dr. Matthew L. Flaherty, Department of Neurology, University of Cincinnati Academic Health Center, 260 Stetson St., Room 2316, Cincinnati, OH 45267-0525 matthew.flaherty{at}uc.edu

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Abbreviations: FDA = Food and Drug Administration; GOS = Glasgow Outcome Scale; IRB = institutional review board; mRS = modified Rankin Scale; NIHSSS = NIH Stroke Scale score; NINDS = National Institute of Neurological Disorders and Stroke; rt-PA = recombinant tissue plasminogen activator; SACHRP = Secretary’s Advisory Committee on Human Research Protections.

Editorial, page 1562

e-Pub ahead of print on August 27, 2008, at www.neurology.org.

The National Institute of Neurological Disorders and Stroke rt-PA Stroke Trial was funded by the National Institute of Neurological Disorders and Stroke. No support was provided for this analysis.

Disclosures: M.L. Flaherty has received compensation for activities with Novo Nordisk and provided a grand rounds presentation sponsored by an unrestricted educational grant from PhotoThera, Inc. J. Karlawish has received compensation for service on a data safety monitoring board with Myriad Pharmaceuticals. J.P. Broderick has received compensation for activities with Ono Pharmaceuticals, Novo Nordisk, and Boehringer-Ingelheim. He has received financial support/grant support from EKOS Corporation, AstraZeneca, and Genentech. D. Kleindorfer has received honoraria from Boehringer-Ingelheim. The remaining authors have no disclosures.

Received January 3, 2008. Accepted in final form March 11, 2008.

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