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(Stroke. 2009;40:1553.)
© 2009 American Heart Association, Inc.

Editorials

To Phase 3 or Not to Phase 3?

Warren W. Wasiewski, MD

From Neurobiological Technologies, Inc, Edgewater, NJ.

Correspondence to Warren W. Wasiewski, MD. E-mail Runnerw3@yahoo.com

Key Words: clinical trials • statistical models • stroke care

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

See related article, pages 1803–1810.

Decisions to progress new chemical entities, biologicals, or new treatment modalities into Phase 3 are usually based on small Phase 2 studies that are designed to assess safety and to explore efficacy.^1–3 Based on these Phase 2 safety studies, both large and small companies have launched large Phase 3 programs that include 2 concurrently run studies, ie, Stroke-Acute Ischemic NXY Treatment (SAINT) I and SAINT II ASP I and Ancrod Stroke Program (ASP) II. When Phase 3 studies have failed to demonstrate efficacy for the whole population under study, subgroup analysis to identify patients who may have benefited from treatment has led to additional Phase 3, subsequently negative studies.⁴ In part as a result of this approach, the number of failed studies for treatment of acute ischemic stroke, especially for neuroprotection, has become legendary.

In this issue, Mandava and Kent⁵ present a model to predict if the results of a single study are different from a pooled control population. The model calculates expected outcome using a pooled control population and the ±95% "prediction interval surfaces" using the baseline variables of the National Institutes of Health Stroke Scale and age. The outcome variables assessed in the model are mortality and the 90-day modified Rankin Scale (mRS) score of 0 to 2. Using this model, they correctly predict the recent failure of SAINT II⁶ based on the results of SAINT I,⁷ because the treatment group outcome in SAINT I was no different from the outcome of . . . [Full Text of this Article]

Related Article:

A Method to Determine Stroke Trial Success Using Multidimensional Pooled Control Functions

Pitchaiah Mandava and Thomas A. Kent
Stroke 2009 40: 1803-1810. [Abstract] [Full Text] [PDF]