Understanding the Placebo Effect in Clinical Trials for Ménière Disease

Introduction: The placebo effect seen in clinical trials complicates the efforts to find better treatments for Meniere’s Disease. The purpose is to assess the scope of the placebo effect for various experimental treatments for Meniere’s Disease.

Methods: A comprehensive literature search in PubMed, SCOPUS, CINAHL, and Cochrane was conducted from inception to September 2022. Randomized controlled trials (RCTs) of adults with MD were included. We calculated mean differences (MD) with 95% confidence interval (CI)for Pure Tone Audiometry (PTA), Speech Discrimination Score (SDS), American Academy of Otolaryngology Functional Level (AAO-FL) and proportion difference for vertigo frequency. Risk of bias in RCTs was assessed using the Cochrane Risk of Bias Tool.

Results: Nine RCT studies involving 545 patients were included in the meta-analysis. Significant improvement was seen in both the experimental group and the placebo group for AAO FL (MD -1.6, [-2.1, -1.1], p< 0.00001) and (MD -0.6, [95% CI -1.2, 0.1], p=0.02), respectively and significant reduction of vertigo frequency at 2 months for experimental group (MD -0.1 [-0.2, -0.0], p=0.001) and placebo group (MD -0.1, [-0.2, -0.0], p=0.008). No significant difference for PTA, SDS, and vertigo frequency at 1 and 3 months. Patient-reported vertigo episodes improved in the experimental group (90.1% [39.2, 65.5]) compared to the placebo group (52.5% [39.2, 65.5]) by 37.6% [21.8, 51.3] (p < 0.0001). Patients who received placebo treatment reported worsening vertigo frequency (17.4% [2.1, 43.0]) compared to those who received experimental treatment (4.2% [0.8, 12.2]) by 13.2% [2.0, 25.3] (p=0.019).

Conclusions: The placebo effect in Meniere’s Disease clinical trials is associated with improvement in functional impact at 1 month, vertigo frequency at 2 months and overall rate of vertigo episodes. Given the influence of follow-up duration, we propose evaluating symptoms for at least 6 months and expanding the arsenal of tools to better assess treatment response. The extent and strength of the placebo effect continues to be a hurdle in the search for better treatment options.