Impact of Syndrome Differentiation on Treatment Effects and side Effects of Chinese Herbal Medicine in Randomized Controlled Trials: A Meta-Epidemiological Study

Abstract

Objective: In Traditional Chinese medicine (TCM), syndrome differentiation is considered to be an essential diagnostic process for tailoring Chinese herbal medicine (CHM) treatments to individual patients. We conducted a meta-epidemiological study to evaluate the potential impact of syndrome differentiation on improving effect estimates in randomized controlled trials (RCTs). Study Design and Setting: Seven databases were searched to identify systematic reviews (SRs) published between 2021 and 2022 that pooled RCTs evaluating CHM treatment effects or side effects. Meta-epidemiological analyses were conducted using a two-step approach. Subgroup analyses were performed based on the disease category, outcome nature, and funding. Results: We included 137 SRs comprising 2,064 RCTs. The results demonstrated small and statistically nonsignificant differences in both treatment effects (ROR: 0.93, 95% confidence interval (CI): 0.86 to 1.00, P = .04 for binary outcomes; dSMD: −1.44, 95% CI: −3.95 to 1.08, P = .26 for continuous outcomes) and side effects (ROR: 1.13, 95% CI: 0.66 to 1.92, P = .66) between RCTs that incorporated syndrome differentiation and those did not. Subgroup analysis showed RCTs of gastrointestinal disease that incorporated syndrome differentiation exhibited a larger magnitude of side effects than that did not. For binary outcomes, subgroup analyses of RCTs of circulatory diseases or those reporting subjective outcomes showed that syndrome differentiation led to a statistically significantly smaller treatment effect. Conclusion: Individualizing CHM treatments through syndrome differentiation provide no significant evidence of improvement in TCM practice outcomes in RCTs. Furthermore, subgroup analyses suggest that syndrome differentiation may be associated with a smaller treatment effect among RCTs of CHM for circulatory diseases and a possible trend toward increased side effects in patients with gastrointestinal diseases.