Clinical trial outcome in neuropathic pain: relationship to study characteristics.
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.
Katz
Jennifer
J
Department of Psychology, State University of New York College at Geneseo, NY, USA.
Finnerup
Nanna B
NB
Dworkin
Robert H
RH
D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000592:standards / Q000706:statistics & numerical data; D003627:Data Interpretation, Statistical; D006801:Humans; D016015:Logistic Models; D015201:Meta-Analysis as Topic; D009437:Neuralgia / Q000188:drug therapy*; D010148:Intractable Pain / Q000188:drug therapy* / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy*; D015990:Placebo Effect; D012107:Research Design / Q000592:standards / Q000706:statistics & numerical data; D018401:Sample Size; D016896:Treatment Outcome
D000700:Analgesics