Joshua Fink, Roy Freeman, Birol Emir, Bruce Parsons

Greater understanding of factors associated with the high placebo-response rates noted in recent neuropathic pain trials may improve trial design. This study investigated placebo response and its predictors in pregabalin trials in patients with diabetic peripheral neuropathy (DPN) or postherpetic neuralgia. Individual patient data from 16 randomized, placebo-controlled, double-blind trials of pregabalin in 3,053 patients with DPN and 1,460 patients with postherpetic neuralgia were pooled (by condition and all together) in order to investigate the placebo response and its predictors. Univariate and multivariate analyses were performed across all 16 trials to identify predictors of change in pain score in patients. Trials with a >2-point mean reduction in pain score at endpoint with placebo were designated high placebo response and were compared with low placebo-response trials (those with a ≤2-point mean reduction) with respect to patient and study characteristics. Three high placebo-response studies were identified, with all in DPN patients and all conducted postapproval of pregabalin. Younger age, higher mean baseline pain score, longer study duration, higher ratio of patients on active treatment to placebo, and study conducted postapproval were all significantly associated with a higher placebo response (P<0.05). There was a trend towards an increased placebo response in all studies over time without any corresponding change in the response to pregabalin. Consideration of the factors identified here as contributing to a higher placebo response could help improve the sensitivity and accuracy of clinical trials in patients with neuropathic pain.