An Investigation of Factors Contributing to Higher Levels of Placebo Response in Clinical Trials in Neuropathic Pain: A Systematic Review and Meta-Analysis

• Published in: Clinical drug investigation 2015-02, Vol.35 (2), p.67-81
• Main Authors: Arakawa, Akio, Kaneko, Masayuki, Narukawa, Mamoru
• Format: Article
• Language: English
• Subjects: Analgesics - therapeutic use; Clinical Trials as Topic; Double-Blind Method; Humans; Internal Medicine; Medicine; Medicine & Public Health; Neuralgia - drug therapy; Pharmacology/Toxicology; Pharmacotherapy; Placebos; Systematic Review
• ISSN: 1173-2563; 1179-1918
• DOI: 10.1007/s40261-014-0259-1

Background In new drug development in neuropathic pain (NeP), randomized, double-blind, placebo-controlled trials (PCTs) with long treatment durations in a parallel-group design are recommended for confirmatory trials. Objective This study was conducted to identify potential factors contributing to elevated placebo response in parallel-group PCTs for oral drugs with at least a 4-week treatment duration. Methods A literature search was conducted through MEDLINE and EMBASE, and was supplemented with data from ClinicalTrials.gov and US/Japanese regulatory approval review information. Using the 30 or 50 % responder rate (RR), logistic regression analyses were performed to investigate the relationship between the degree of placebo response and several potential influencing factors. Results The search identified 71 trials ( n  = 6,126). The estimated 50 % RRs (95 % confidence intervals) in the placebo group were as follows: peripheral neuropathic pain (P-NeP) 23 % (21, 26 %); central neuropathic pain (C-NeP) 14 % (10, 19 %); postherpetic neuralgia (PHN) 19 % (15, 24 %); painful diabetic peripheral neuropathy (pDPN) 26 % (23, 29 %); posttraumatic peripheral neuropathic pain (PT) 15 % (10, 20 %). From the logistic regression analyses, it was found that there was a significant association between placebo response (50 % RR and 30 % RR) and NeP classification ( P