Abstract
Background
Predicting the nocebo response in randomized controlled trials (RCTs) is crucial as it can help minimize its influence and improve the evaluation of the side effects of interventions for ADHD. The aim of this study is to determine the effect of covariates related to study design, intervention, and patients' characteristics on the nocebo response in patients with Attention Deficit Hyperactivity Disorder (ADHD) using Metaforest, and, ultimately, to investigate Metaforest's performance in predicting nocebo response in ADHD RCTs.
Methods
This study is a secondary analysis of a previously published systematic review. Nocebo response was defined as the proportion of patients experiencing at least one adverse event (AE) while receiving a placebo. We used Metaforest for investigating patient-, intervention-, and study design–related nocebo response moderators in ADHD RCTs.
Results
One hundred and five studies were included. Overall, 55.4% of patients experienced at least one AE while receiving placebo. However, between-study variability in nocebo response was very high, ranging from 4.2% to 90.2%, leading to high statistical heterogeneity (I² = 88.3%). Older patients showed a higher nocebo response. The moderating effects of the year of publication, treatment length, and gender were also significant. The predictive performance of the model was low to moderate (R² test = 0.1922; MSE = 0.0408).
Conclusion
Age was the most important nocebo response modifier, followed by year of publication, treatment length, and gender. Metaforest lacked the capability to accurately predict nocebo responses in future studies.