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(Stroke. 2006;37:2878.)
© 2006 American Heart Association, Inc.

Letters to the Editor

Differences in Response to Reperfusion Therapies in Acute Stroke Between Men and Women: Mediated by Sex or by Chance?

Institute for Clinical Research and Health Policy Studies, Tufts-New England Medical Center, Boston, Mass

Michael D. Hill, MD, MS

Foothills Hospital, Calgary, Alberta, Canada

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

To the Editor:

Drs Sandercock and Lewis remind us of some of the very real hazards of subgroup analysis. Performing multiple "one-variable-at-time" subgroup analyses will inevitably yield spurious results.^1,2 This problem of spurious false-positive results, however, is not one that is directly addressed by increased sample size or statistical power, as they imply. Further, they seem to argue that the proper response to the risk of spurious false-positive results is to cease all analyses on variation in the effect of thrombolysis in stroke until the IST-3 Trial is completed. We respectfully disagree.

Although multiple "one-variable-at a-time" subgroup analyses may sometimes yield misleading results, for treatments with both risks and benefits such as recombinant tissue plasminogen activator for stroke, reporting only the summary result is also likely to be misleading, because the average effect might not even reflect the risk-benefit trade-offs seen in typical patients within the trial.^1–3 This is a true dilemma, and we believe that both terms of this dilemma deserve respect (because patients are harmed by type II as well as by type I error). Although completely satisfactory solutions to this dilemma may not be possible, one approach that we believe has promise is the use of extant databases to develop multivariate risk-benefit models.^1–3 These models, informed in part by subgroup analyses such as ours, can then be used to explore treatment-effect heterogeneity when future randomized clinical trial data become available. Hypothesis-generating analyses on "old data" can guide a priori hypothesis-driven analyses on new data (as Sandercock and . . . [Full Text of this Article]

This article has been cited by other articles:

				D. M. Kent, A. M. Buchan, and M. D. Hill The gender effect in stroke thrombolysis: Of CASES, controls, and treatment-effect modification Neurology, September 30, 2008; 71(14): 1080 - 1083. [Abstract] [Full Text] [PDF]