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(Stroke. 2009;40:1029.)
© 2009 American Heart Association, Inc.

Editorials

Surrogate Outcomes

A Cautionary Note

Joanna M. Wardlaw, MD

From the Division of Clinical Neurosciences, Western General Hospital, Edinburgh, UK.

Correspondence to Joanna M. Wardlaw, Division of Clinical Neurosciences, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK. E-mail joanna.wardlaw@ed.ac.uk

Key Words: outcome • diffusion-weighted imaging • acute ischemic stroke • surrogate outcome • thrombolysis

An extract of the first 250 words of the full text is provided, because this article has no abstract.

See related article, pages 1353–1358.

Drug development for acute stroke treatments is complex, very expensive, very time-consuming, and frequently disappointing. Surrogate outcome theory states that new therapies for stroke could be evaluated with smaller sample sizes than are required when traditional functional outcome measures are used by using surrogate outcomes in clinical trials. This would enable new therapies to be discarded or confirmed as candidates for larger definitive clinical trials more rapidly than at present.

This theory presupposes that surrogate outcomes work by removing the "noise" inherent in all clinically based assessments so that the therapeutic "signal" can be detected more clearly, thus requiring fewer patients to achieve a positive result. It also assumes that the effect of the treatment on the surrogate outcome profiles the therapeutic signal equally and uniformly across all key clinical characteristics (like stroke severity or age). Thus, it assumes that the surrogate mirrors both the beneficial effects and risks so that no systematic bias is inadvertently introduced that might skew the results away from the true therapeutic effect. Smaller samples should reduce costs, speed up drug assessments, and hence enable effective treatments to be found more quickly. It is therefore understandable why surrogates appear attractive, particularly for future trials in acute ischemic stroke, an area in which the discovery of effective new treatments has proved elusive.

Imaging has the potential to provide various surrogate outcome markers for acute ischemic stroke trials. Evidence of ischemic tissue injury is easy to see and appears simple to . . . [Full Text of this Article]

Related Article:

Expediting MRI-Based Proof-of-Concept Stroke Trials Using an Earlier Imaging End Point

Martin Ebinger, Soren Christensen, Deidre A. De Silva, Mark W. Parsons, Christopher R. Levi, Kenneth S. Butcher, Christopher F. Bladin, P. Alan Barber, Geoffrey A. Donnan, Stephen M. Davis for the EPITHET Investigators
Stroke 2009 40: 1353-1358. [Abstract] [Full Text] [PDF]