Effect of variability in the 7-day baseline pain diary on the assay sensitivity of neuropathic pain randomized clinical trials: an ACTTION study.
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.
Department of Biostatistics and Epidemiology, Anesthesiology, and Neurology, University of Pennsylvania, Philadelphia, PA, USA University of Pennsylvania, Philadelphia, PA, USA Queen's University, Kingston, ON, Canada Pain Research Informatics, Multimorbidities and Education Center, VA Connecticut Healthcare, New Haven, CT, USA Department of Psychiatry, Yale University, New Haven, CT, USA Analgesic Solutions, Natick, MA, USA Tufts University, Boston, MA, USA United States Food and Drug Administration, Silver Spring, MD, USA California Pacific Medical Center Research Institute, San Francisco, CA, USA University of Washington, Seattle, WA, USA University of Rochester, Rochester, NY, USA.
John T
JT
Farrar
Andrea B
AB
Troxel
Kevin
K
Haynes
Ian
I
Gilron
Robert D
RD
Kerns
Nathaniel P
NP
Katz
Bob A
BA
Rappaport
Michael C
MC
Rowbotham
Ann M
AM
Tierney
Dennis C
DC
Turk
Robert H
RH
Dworkin
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000588:Amines / Q000627:therapeutic use; D000700:Analgesics / Q000627:therapeutic use; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D005260:Female; D000077206:Gabapentin; D006801:Humans; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000188:drug therapy*; D051474:Neuralgia, Postherpetic / Q000188:drug therapy*; D010147:Pain Measurement; D000069583:Pregabalin; D016032:Randomized Controlled Trials as Topic; D057566:Self Report; D016896:Treatment Outcome; D014481:United States; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000627:therapeutic use
D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin
Assay sensitivity; Neuropathic pain; Pain measurement; Randomized controlled trials as topic; Reproducibility of results; Research design; Treatment efficacy