Background Recognizing the importance of assessing Chinese herbal medicine (CHM) for effectiveness and safety, the integration of syndrome differentiation (SD) into randomized controlled trials (RCTs) remains limited. A previous meta-epidemiological study found no significant benefits when SD-guided CHM prescription, with concerns arising over increased side effects in gastrointestinal disease RCTs. To address this, a two-part study was conducted.

Methods In Part 1, a two-round Delphi study was conducted to prioritize gastrointestinal diseases sensitive to SD using a GRADE Evidence to Decision framework. The study involved a panel comprising conventional physicians with Chinese medicine training (n=4), Chinese medicine practitioners (n=6), and clinical research methodologists (n=2). Gastroesophageal reflux disease (GERD) emerged as the focal point for Part 2: Network Meta-analysis (NMA). NMA aimed to evaluate the comparative effectiveness and safety of CHM treatments with or without SD (NSD). Primary outcomes included symptom relief rate, with secondary outcomes including symptom score changes assessed by the reflux disease questionnaire (RDQ) or GERD questionnaire (GERDQ), adverse event rate, and recurrence rate. NMA results were interpreted using a minimally contextualized framework, and the quality of evidence was assessed using the GRADE approach.

Results Delphi participants considered the use of SD to potentially impact the effectiveness and safety of treatment in managing GERD, chronic atrophic gastritis, functional dyspepsia, and irritable bowel syndrome with CHM. GERD was selected as the primary focus for NMA. In Part 2, 34 eligible RCTs involving 4,226 participants and 28 different CHM formulas were analyzed. NMA results indicated that CHM prescribed without SD may exhibit greater effectiveness across all measured outcomes, except for changes in GERDQ scores. Among these, Chaishao Liujunzi Tang He Wubei San (NSD) showed potential as the most effective option for symptom relief and RDQ score improvement, albeit with low-certainty evidence.

Conclusions The varied opinions within the Delphi panel highlight uncertainties about SD’s role in CHM treatments. NMA suggests CHM without SD may be more effective for GERD, but further research is needed to understand the value of Traditional Chinese Medicine diagnoses in tailoring CHM interventions for gastrointestinal conditions sensitive to SD.