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From the Department of Psychology (J.K.), State University of New York College at Geneseo; the Departments of Anesthesiology (J.K., R.H.D.) and Neurology (R.H.D.), University of Rochester School of Medicine and Dentistry, NY; and the Department of Neurology (N.B.F.), Aarhus University Hospital, Denmark.
Address correspondence and reprint requests to Dr. Robert H. Dworkin, Department of Anesthesiology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 604, Rochester, NY 14642 robert_dworkin{at}urmc.rochester.edu
Background: Several recent randomized clinical trials have found that the medications being evaluated for neuropathic pain did not significantly differ from placebo for the primary efficacy endpoint, despite encouraging results from prior preclinical and clinical studies. It is unclear whether these trials were unsuccessful because the medications truly lack efficacy or whether characteristics of the trials compromised the demonstration of treatment benefits.
Objective: To identify factors associated with positive (i.e., favors medication) vs negative outcomes of placebo-controlled neuropathic pain trials.
Methods: We examined study characteristics associated with positive vs negative clinical trial outcomes for neuropathic pain treatments using the information provided in a comprehensive meta-analysis and additional ratings for 106 clinical trials.
Results: Univariate analyses indicated that the results of medication vs placebo comparisons were more likely to be positive when medication response rates were greater, placebo response rates were lower, and studies were published earlier. In a multivariate analysis performed to identify independent contributions of study characteristics to trial outcomes, greater medication response, reduced placebo response, and larger sample sizes were each uniquely associated with positive outcomes. In addition, greater medication response rates and parallel groups designs were each independently associated with greater placebo response rates.
Conclusions: The results suggest that study characteristics may contribute to the outcomes of clinical trials of treatments for neuropathic pain and provide an impetus for investigating strategies for decreasing placebo response rates and thereby possibly increasing the likelihood of positive outcomes in trials of efficacious treatments.
Abbreviations: NNT = numbers needed to treat; NRS = numerical rating scale; VAS = visual analogue scale.
Supplemental data at www.neurology.org
Editorial, page 250
e-Pub ahead of print on October 3, 2007, at www.neurology.org.
Disclosures: The authors shared responsibility for performing the analyses reported in this article, and no support was received from any external source for this research or its publication. N.B.F. has received research support or honoraria in the past year from Neurosearch A/S and UCB Nordic. R.H.D. has received research support, consulting fees, or honoraria in the past year from Allergan, CombinatoRx, Dara, Dov, Eli Lilly, Endo, EpiCept, Fralex, GlaxoSmithKline, GW Pharmaceuticals, Johnson & Johnson, KAI Pharmaceuticals, Merck, NeurogesX (also stock options), Novartis, Pfizer, Schwarz Pharma, Supernus, US Food and Drug Administration, US National Institute of Health, US Veterans Administration, Wyeth, and XTL Biopharmaceuticals. J.K. reports no potential conflicts of interest.
Received January 19, 2007. Accepted in final form May 22, 2007.
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