Abstract
Background Understanding factors associated with high placebo responses in clinical trials increases the likelihood of detecting a meaningful treatment effect. The aim of the present study was to identify subject-level factors that contribute to placebo variability in patients with neuropathic pain due to spinal cord injury (SCI). Methods Multiple regression analysis of patient data from randomized, double-blind, placebo-controlled trials (duration >4 weeks) involving individuals with SCI was performed. Patient demographics, as well as injury and pain characteristics were examined for their association with changes in pain rating from baseline to the end of the trial (i.e., placebo response). The overall effect of individual predictors was quantified with meta-analysis statistics. Results A total of 276 patients with SCI from six studies were included in the analysis. Based on the meta-analysis of subject-level predictors, larger placebo responses were associated with male subjects (β=0.635; standard error [SE]=0.262; =0.016) and higher baseline pain (β=-0.146; SE=0.073; =0.044). There were no significant effects for injury characteristics (i.e., severity, level, and time since injury) or pain characteristics (i.e., location and evoked). No significant publication bias was detected. Conclusion The current meta-analysis of individual patient data demonstrated the importance of sex and baseline pain intensity on changes in pain ratings in the placebo arm of SCI central neuropathic pain randomized controlled clinical trials. Overall, our findings indicate that placebo responses occur independent of injury characteristics.
Jutzeler, Catherine R