Impact of Different Dosage Forms of Orally Administered Chinese Herbal Medicine on Treatment and Adverse Effect Estimates in Randomized Controlled Trials: A Meta-Epidemiological Study.

AIM: In traditional Chinese medicine, different dosage forms of orally administered Chinese herbal medicine (CHM) may introduce bias in estimating treatment and adverse effects. This meta-epidemiological study aimed to evaluate whether the use of different orally administered CHM dosage forms is associated with overestimation or underestimation of treatment and adverse effects in randomized controlled trials (RCTs).

METHODS: Seven electronic databases were searched to identify potentially eligible meta-analyses (MAs) of RCTs evaluating CHM interventions. A two-step meta-epidemiological analysis was performed, using ratios of odds ratios for binary outcomes and differences in standardized mean differences for continuous outcomes. These metrics assessed whether different orally administered CHM dosage forms-including CHM decoctions, Chinese patent medicines (CPMs), and CHM granules influenced the magnitude of reported treatment effects or adverse effects.

RESULTS: Eighty-two MAs comprising 1263 RCTs were analyzed. Overall, there was no consistent evidence that any oral dosage form systematically overestimated or underestimated treatment effects or adverse effects. Sensitivity analyses confirmed these findings, with the exception that CHM decoctions showed slightly larger binary treatment effects compared to CPMs after adjusting for incomplete outcome data. However, when adjusted for all confounders, CPMs yielded significantly greater continuous treatment effects than CHM decoctions. Additionally, CHM granules were associated with larger continuous treatment effects than CHM decoctions after adjusting for RCT funding. Subgroup analyses indicated that RCTs on digestive diseases tended to report larger effect estimates when using CHM decoctions, whereas RCTs on endocrine, nutritional, and metabolic diseases tended to report larger effect estimates when using CPMs.

CONCLUSIONS: This meta-epidemiological study suggests that while oral dosage forms of CHM are associated with minimal differences in reported treatment and adverse effect estimates, specific dosage forms may offer advantages in certain contexts. Subgroup analyses indicate that digestive disease trials tend to report larger estimates with CHM decoctions, and endocrine/metabolic disease trials with CPMs. When adjusting for confounders, CPMs yield greater continuous treatment effects compared with CHM decoctions, while CHM granules are associated with larger estimates than CHM decoctions after adjusting for RCT funding. Further research is needed to confirm their clinical relevance and guide formulation choices in CHM practice.