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Pain. 2014 Aug;155(8):1622-31. doi: 10.1016/j.pain.2014.05.009. Epub 2014 May 14.

Effect of variability in the 7-day baseline pain diary on the assay sensitivity of neuropathic pain randomized clinical trials: an ACTTION study.

Author information

  • 1Department of Biostatistics and Epidemiology, Anesthesiology, and Neurology, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: jfarrar@upenn.edu.
  • 2University of Pennsylvania, Philadelphia, PA, USA.
  • 3Queen's University, Kingston, ON, Canada.
  • 4Pain Research Informatics, Multimorbidities and Education Center, VA Connecticut Healthcare, New Haven, CT, USA; Department of Psychiatry, Yale University, New Haven, CT, USA.
  • 5Analgesic Solutions, Natick, MA, USA; Tufts University, Boston, MA, USA.
  • 6United States Food and Drug Administration, Silver Spring, MD, USA.
  • 7California Pacific Medical Center Research Institute, San Francisco, CA, USA.
  • 8University of Washington, Seattle, WA, USA.
  • 9University of Rochester, Rochester, NY, USA.

Abstract

The degree of variability in the patient baseline 7-day diary of pain ratings has been hypothesized to have a potential effect on the assay sensitivity of randomized clinical trials of pain therapies. To address this issue, we obtained clinical trial data from the Food and Drug Administration (FDA) through the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership, and harmonized patient level data from 12 clinical trials (4 gabapentin and 8 pregabalin) in postherpetic neuralgia (PHN) and painful diabetic peripheral neuropathy (DPN). Models were developed using exploratory logistic regression to examine the interaction between available baseline factors and treatment (placebo vs active medication) in predicting patient response to therapy (ie, >30% improvement). Our analysis demonstrated an increased likelihood of response in the placebo-treated group for patients with a higher standard deviation in the baseline 7-day diary without affecting the likelihood of a response in the active medication-treated group, confirming our hypothesis. In addition, there was a small but significant age-by-treatment interaction in the PHN model, and small weight-by-treatment interaction in the DPN model. The patient's sex, baseline pain level, and the study protocol had an effect only on the likelihood of response overall. Our results suggest the possibility that, at least in some disease processes, excluding patients with a highly variable baseline 7-day diary has the potential to improve the assay sensitivity of these analgesic clinical trials, although reductions of external validity must be considered when increasing the homogeneity of the investigated sample.

Copyright © 2014 International Association for the Study of Pain. All rights reserved.

KEYWORDS:

Assay sensitivity; Neuropathic pain; Pain measurement; Randomized controlled trials as topic; Reproducibility of results; Research design; Treatment efficacy

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