Sleep improvement for restless legs syndrome patients. Part IV: meta-analysis comparison of effect sizes of vibratory stimulation sham pads and placebo pills

Abstract

Purpose:

To determine whether sham pads used as controls in randomized clinical trials of vibratory stimulation to treat patients with sleep loss associated with restless legs syndrome perform differently than placebo pills used in comparable restless legs syndrome drug trials.

Patients and methods:

Sham pad effect sizes from 66 control patients in two randomized clinical trials of vibratory stimulation were compared with placebo responses from 1,024 control patients in 12 randomized clinical drug trials reporting subjective sleep measurement scales. Control patient responses were measured as the standardized difference in means corrected for correlation between beginning and ending scores and for small sample sizes.

Results:

For parallel randomized clinical trials, sham effects in vibratory stimulation trials were not significantly different from placebo effects in drug trials (0.37 and 0.31, respectively, Q_{between subgroups} =0.25, P_Q≥0.62). Placebo effect sizes were significantly smaller in crossover drug trials than sham effect sizes in parallel vibratory stimulation trials (0.07 versus 0.37, respectively, Q_{between subgroups} =4.59, P_Q≤0.03) and placebo effect sizes in parallel drug trials (0.07 versus 0.31, respectively, Q_{between subgroups} =5.50, P_Q≤0.02).

Conclusion:

For subjective sleep loss assessments in parallel trials, sham pads in vibratory stimulation trials performed similarly to placebo pills in drug trials. Trial design (parallel versus crossover) had a large influence on control effect sizes. Placebo pills in crossover drug trials had significantly smaller effect sizes than sham pads in parallel vibratory stimulation trials or placebo pills in parallel drug trials.

Keywords::

• sham effect
• placebo effect
• trial design
• crossover study
• parallel study
• counterstimulation

Disclosure

Financial support for the study was provided by Sensory Medical, Inc, San Clemente, CA, USA. The author is the Chief Executive Officer of Sensory Medical, Inc, and a minority shareholder. The author reports no other conflicts of interest.