Systematic review and meta-analysis of placebo/sham controlled randomised trials of spinal cord stimulation for neuropathic pain

Abstract

The aims of this review were to systematically identify the current evidence base of placebo (or "sham") randomised controlled trials (RCTs) of spinal cord stimulation (SCS) for neuropathic pain and to undertake a meta-analysis to investigate the effectiveness of SCS when compared with a placebo comparator arm. Electronic databases were searched from inception until January 2019 for RCTs of SCS using a placebo/sham control. Searches identified 8 eligible placebo-controlled randomised trials of SCS for neuropathic pain. Meta-analysis shows a statistically significant reduction in pain intensity during the active stimulation treatment periods compared with the control treatment periods, pooled mean difference -1.15 (95% confidence interval -1.75 to -0.55, P = 0.001) on a 10-point scale. Exploratory study-level subgroup analysis suggests a larger treatment effect in RCTs using a placebo control (defined as studies where the device was inactive and at least one of the study procedures was different between the arms) than a sham control (defined as all study procedures being equal between arms including SCS device behaviour). Our findings demonstrate limited evidence that SCS is effective in reducing pain intensity when compared with a placebo intervention. Our analyses suggest that the magnitude of treatment effect varies across trials and, in part, depends on the quality of patient blinding and minimisation of carryover effects. Improved reporting and further methodological research is needed into placebo and blinding approaches in SCS trials. Furthermore, we introduce a differentiation between placebo and sham concepts that may be generalisable to trials evaluating surgical or medical procedures.