The Power of Placebo to Restore Neurological Function After Spinal Cord Injury: Implications for Neuromodulation.

Background: Emerging trials demonstrate that neuromodulation, especially spinal cord stimulation, improves function for those with chronic spinal cord injury. Their design - uncontrolled and unblinded - is justified by the claim that sham conditions are unethical and/or impossible. In the absence of controlled trials, the functional benefits of spinal cord stimulation cannot be distinguished from the effects of placebo.

Objectives: To discuss the validity of the claim that placebo control conditions are infeasible in spinal cord stimulation research, and to propose feasible solutions for including sham conditions that would account for placebo effects.

Results: Placebo effects are likely to occur in spinal cord stimulation studies, given the high levels of participant expectations of an effect, natural fluctuations in symptoms associated with spinal cord injury, regression towards the mean, the Hawthorne effect, presence of concurrent interventions, and the absence of blinding in existing studies. Options for placebo control conditions could include adding an "untreated" control group, using "placebo-resistant" outcomes, adding an active comparator group or sham stimulation, or investing in parasthesia-free stimulation. Additionally, wherever feasible, blinding of both participants and assessors should be pursued.

Conclusions: The current evidence base for spinal cord stimulation is undermined by the lack of rigorous sham controls, and the argument that such controls are unethical or unfeasible do not withstand scrutiny. We propose strategies for the inclusion of placebo controls in future trials and encourage investigators to prioritize these approaches to ensure the true benefit of spinal cord stimulation can be determined.