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

ObjectiveIn 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 SettingSeven 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.ResultsWe 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.ConclusionIndividualizing 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.