This Article Full Text Full Text (PDF) All Versions of this Article: 36/6/1341    most recent 01.STR.0000165931.77045.eev1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Krams, M. Articles by Berry, D. A. Search for Related Content PubMed PubMed Citation Articles by Krams, M. Articles by Berry, D. A. Related Collections Emergency treatment of Stroke Other Stroke Treatment - Medical

(Stroke. 2005;36:1341.)
© 2005 American Heart Association, Inc.

Emerging Therapies

The Past Is the Future

Innovative Designs in Acute Stroke Therapy Trials

Michael Krams, MD; Kennedy R. Lees, MD Donald A. Berry, PhD

From Pfizer Global Research and Development (M.K.), Groton, Conn; the University Department of Medicine and Therapeutics (K.R.L.), Gardiner Institute, Western Infirmary, Glasgow, UK; and the Department of Biostatistics (D.A.B.), M. D. Anderson, Houston, Tex.

Correspondence to Prof Donald A. Berry, Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 447, Houston, TX 77030. E-mail dberry@mdanderson.org

Section Editors: Marc Fisher MD Antoni Dávalos MD

Key Words: models, theoretical • neuroprotection

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

	Introduction

 
More than 74 000 patients with acute ischemic stroke have been randomized into clinical trials over the past 35 years to investigate new therapies.¹ Only one treatment, thrombolysis with recombinant tissue plasminogen activator, has emerged from these investigations.² Efforts to establish acute neuroprotectant therapies have yet to succeed.^3,4

Have we squandered our resources? Has methodological rigidity delayed development of a new treatment or prolonged investigation of an ineffective therapy? Here we present a flexible and more efficient approach to clinical trial design and analysis. We have the potential to improve the use of scarce patient resources and to accelerate development of promising agents.

In medical practice, we respond to a patient if a dosage seems inadequate by either changing the dosage or switching to another medication. We cautiously change treatment after reviewing new evidence: side effects, intractable symptoms, and poor adherence. We might express our estimate of how much the change may improve the patient’s condition in terms of probability. We repeat this process every time we update the treatment plan in light of new important information. Why not take the same approach to clinical trials?

The proposed approach to the design and conduct of clinical trials uses Bayesian methods that make careful use of high-quality available past (prior) evidence to refine the inference from accumulating evidence in the ongoing clinical trial. This approach may: (1) enhance investigation of single agents or combination therapies; (2) make earlier and more reliable choices of dose for use in pivotal trials; (3) accelerate . . . [Full Text of this Article]

This article has been cited by other articles:

				G. Howard Nonconventional Clinical Trial Designs: Approaches to Provide More Precise Estimates of Treatment Effects With a Smaller Sample Size, but at a Cost Stroke, February 1, 2007; 38(2): 804 - 808. [Abstract] [Full Text] [PDF]

				B. H. Dobkin Rehabilitation and Functional Neuroimaging Dose-Response Trajectories for Clinical Trials Neurorehabil Neural Repair, December 1, 2005; 19(4): 276 - 282. [Abstract] [PDF]