Assay sensitivity and study features in neuropathic pain trials
An ACTTION meta-analysis
Abstract
Objective:
Our objective was to identify patient, study, and site factors associated with assay sensitivity in placebo-controlled neuropathic pain trials.
Methods:
We examined the associations between study characteristics and standardized effect size (SES) in a database of 200 publicly available randomized clinical trials of pharmacologic treatments for neuropathic pain.
Results:
There was considerable heterogeneity in the SESs among the examined trials. Univariate meta-regression analyses indicated that larger SESs were significantly associated with trials that had 1) greater minimum baseline pain inclusion criteria, 2) greater mean subject age, 3) a larger percentage of Caucasian subjects, and 4) a smaller total number of subjects. In a multiple meta-regression analysis, the associations between SES and minimum baseline pain inclusion criterion and age remained significant.
Conclusions:
Our analyses have examined potentially modifiable correlates of study SES and shown that a minimum pain inclusion criterion of 40 or above on a 0 to 100 scale is associated with a larger SES. These data provide a foundation for investigating strategies to improve assay sensitivity and thereby decrease the likelihood of falsely negative outcomes in clinical trials of efficacious treatments for neuropathic pain.
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Information & Authors
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Copyright
© 2013 American Academy of Neurology.
Publication History
Received: October 3, 2012
Accepted: March 13, 2013
Published online: May 22, 2013
Published in print: July 2, 2013
Disclosure
The views expressed in this article are those of the authors and no official endorsement by the FDA or the pharmaceutical companies that provided unrestricted grants to support the activities of ACTTION should be inferred. R.H. Dworkin has received in the past 2 years research support from the FDA (HHSF 223201000078C; U01 FD004187-01) and the US NIH (1R01 AR059102-01A) and personal compensation for activities involving clinical trial research methods and/or reimbursement of travel expenses associated with these activities from Adynxx, Allergan, Analgesic Solutions, Anika, Astellas, Avanir, Axsome, Bayer, Biogen, Bioness, Bristol-Myers Squibb, Cardiome, Collegium, Depomed, Depuy, Eli Lilly, Epicept, Flexion, Genzyme, Glenmark, Inhibitex, Johnson & Johnson, Medicinova, Merck, MMS Holdings, NeurogesX, Ono, Pfizer, Phillips, Prolong, Q-Med, Regenesis, Sanofi-Aventis, Smith & Nephew, Spinifex, Takeda, Taris, Teva, Theravance, and Xenon. D.C. Turk has received research support from Endo, Johnson & Johnson, Philips Respironics, the US NIH (NIAMS R01AR059102; NIDA 1R01DA032776, 1R01DA026887), and the FDA (HHSF223201000078C; U01 FD004187), and consulting fees from Eli Lilly, Ortho-McNeill Janssen, Pfizer, Philips Respironics, and SK LifeScience in the past 2 years. S. Peirce-Sandner and H. He report no disclosures. M.P. McDermott has served on Scientific Advisory Boards for the ALS Association, Biogen, Isis, and Muscular Dystrophy Association; has received research support from the US Centers for Disease Control and Prevention, FDA, US NIH, and the American Dental Association, Boehringer Ingelheim, Endo, Forest, Medivation, Michael J. Fox Association, Muscular Dystrophy Association, NeuroSearch Sweden, Pfizer, and Spinal Muscular Atrophy Foundation; and has received consulting fees from Bioness, Impax, New York State Department of Health, Smith & Nephew, Synosia, and Teva. J.T. Farrar has served in unpaid roles with the American Pain Society, Institute of Medicine, and National Academy of Science; has received research support from US government grants (UL1-RR024133; U01-AG030644; R01-CA158243; VA-DOD Subcontract D45061; DOD subcontract BD514845; R01-AR064153); and a foundation grant from Altarum, Inc. that serves as a contractor for the NIH Center of Excellence in Pain Education; and a research grant from Depomed, Inc.; and has served as a consultant to AstraZeneca, Bristol-Myers Squibb, Covidien, Dara, Depomed, Dr. Reddy’s Laboratories, Forest, Janssen, Johnson & Johnson, Merck, Prolong, Teva, and United Biosource. N.P. Katz is the owner of Analgesic Solutions, which has multiple pharmaceutical industry clients. A.H. Lin and B.A. Rappaport report no disclosures. M.C. Rowbotham has received consulting income from Abbott, Allergan, Arcion, Bristol-Myers Squibb, Cardiome, Kyowa, Nektar, Xenon, and Zalicus; served on a Scientific Advisory Board for Adynxx, Galderma, and Sanofi; and holds stock options in Afferent Pharmaceuticals. Go to Neurology.org for full disclosures.
Study Funding
Financial support for this project was provided by a research contract (HHSF 223201000078C) from the FDA to the University of Rochester, and by the ACTTION public-private partnership with the FDA, which has received research grants or other revenue from the FDA, various pharmaceutical companies, and other sources.
Authors
Author Contributions
All authors contributed to study concept or design, data interpretation, and critical review and revision of the manuscript. Dr. Dworkin drafted the manuscript except for the statistical analysis section, and Drs. He and McDermott performed the statistical analyses and drafted the statistical analysis section of the manuscript.
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