Nocebo response intensity and influencing factors in the randomized clinical trials of functional dyspepsia: A systematic review and meta-analysis.

OBJECTIVES

In this study we aimed to evaluate the nocebo response rate in patients with functional dyspepsia (FD) and to explore its influencing factors.

METHODS

A literature search of the EMBASE, PubMed, and Cochrane Library databases was conducted for all articles published up to March 2021. Randomized, parallel-designed, placebo-controlled trials on pharmacological interventions for patients with FD were included. A meta-analysis that utilized random effects to analyze the incidence of adverse events (AEs) among participants who were given placebo was conducted, and the correlation between trial characteristics and the magnitude of the nocebo response rate was analyzed.

RESULTS

Altogether, 27 studies including 1866 paitents were deemed eligible and included in the analysis. The total nocebo response rate was 26% (95% confidence interval [CI] 18%-33%). The most frequently reported AEs included nasopharyngitis (9%), constipation (6%), headache (5%), and diarrhea (3%). There were significant differences in nocebo response rates among studies conducted in different country or region, treatment duration, types of medication, sponsorship and different versions of the Rome criteria used for FD diagnosis. While number of centers engaged in the study, types of FD diagnosis and dosing frequency were not significantly associated with the nocebo response rate.

CONCLUSIONS

Patients with FD exhibit notable nocebo response strength in clinical trials. The researchers should adopt a more careful approach when analyzing the relationships between AEs and interventions in such trials.