In traditional Chinese medicine (TCM) clinical research, patients often have strong preferences for TCM therapies. In addition, non-pharmacological interventions such as acupuncture and tuina make effective blinding of patients and practitioners difficult, which may introduce Hawthorne effects and resentful demoralization. Conventional randomized controlled trials also face challenges, including poor recruitment, high dropout rates, and increased bias risk, which limit research efficiency and evidence quality. The Zelen design provides a promising methodological solution to these issues.

This study presents a methodological analysis of the Zelen design for TCM real-world studies, with three focal contributions: (Ⅰ) in-depth feasibility analysis of the Zelen design tailored to the complexities of TCM interventions; (Ⅱ) a simulated TCM trial including a worked example of complier average causal effect (CACE) analysis, with discussion of its idealized assumptions and the need for sensitivity analyses; and (Ⅲ) an in depth examination of ethical safeguards and statistical methods for managing contamination. Key considerations reviewed include trial registration, ethical requirements, sample size calculation, blinding, appropriate applications, and TCM-specific outcome measures.

This analysis identifies key barriers to broader implementation of the Zelen design for evaluating TCM efficacy evaluation, including ethical and regulatory uncertainty surrounding the randomization-before-consent process, a lack of dedicated methodological guidelines and statistical tools, and the inherent complexity of TCM interventions, which heightens contamination risk and complicates compliance definition, while also assessing the overall value of design. Despite these challenges, the Zelen design demonstrates clear advantages in improving patient recruitment and treatment adherence while preserving the benefits of randomization.

The Zelen design offers a balanced pathway that integrates scientific rigor with clinical practicality, and further refinement of design strategies tailored to TCM characteristics is warranted. Future efforts should prioritize methodological innovation and standardization to improve the overall quality of real-world studies in TCM.

In recent years, guidelines and consensus statements have recommended Chinese patent medicines (CPMs) for the treatment of functional constipation (FC). The latest Chinese Health Care Directory also lists CPMs for FC; however, the supporting evidence remains insufficient. In this study, we aimed to evaluate the effectiveness and safety of CPMs in the treatment of FC using a network-meta-analysis (NMA).

We searched for eligible randomized controlled trials (RCTs) published in the databases of PubMed, Cochrane Library, Embase, SinoMed, China National Knowledge Infrastructure, Wanfang, and Chinese Scientific Journals Database. Bayesian NMA and pairwise comparisons were performed to determine the frequency of spontaneous bowel movements, clinical effects, recurrence rate, dyschezia score, and defecation time score.

A total of 61 studies were included. The methodological quality of the included studies was relatively poor, and the reliability of the synthetic outcomes was low. Our findings indicate that in older individuals, according to the self-established clinical efficacy criteria, Liuwei Anxiao combined with prokinetics demonstrated superior clinical effectiveness compared to prokinetic monotherapy (risk ratio [RR]: 1.46, 95% confidence interval [CI]: 1.17, 1.96), with lower scores for defecation times (mean difference: −0.30, 95% CI: −0.60, −0.02). Dalitong granules combined with prokinetics showed better clinical efficacy than prokinetic monotherapy (RR: 1.59, 95% CI: 1.03, 2.53). In older participants, based on published clinical efficacy criteria, Shouhui Tongbian capsule combined with an osmotic laxative exhibited superior clinical effectiveness compared to osmotic laxative monotherapy (RR: 1.21, 95% CI: 1.00, 1.48). Reported adverse events included stomachache, diarrhea, and nausea.

Several positive outcomes were observed, including better clinical effects across different criteria and lower defecation frequency scores. However, the quality of the included studies and the conclusions on CPM coverage areas were limited. Future research should include more high-quality studies directly comparing the effects of different CPMs.

To evaluate the effectiveness and safety of fire needling for herpes zoster from randomized clinical trials (RCTs).

We searched Cochrane Central Register of Controlled Trials, Pubmed, Sino-Med, CNKI, VIP, WanFang databases, and conference proceedings to November, 2017. RCTs were eligible if they tested fire needling for treating herpes zoster more than 3 times. Two authors screened all references, assessed the risk of bias, extracted data, independently, and analyzed data using Trial Sequential Analysis (TSA). Treatment effects were presented as risk ratio (RR) for binary data and standardized mean difference (SMD) for continuous data with 95% confidence interval (CI).

We included 27 RCTs with a total of 1933 participants. Only one RCT had low risk of bias, and the others were of high or moderate risk of bias. For total effectiveness rate (proportion of total number of people who were cured or significant symptom improved), there was no significant difference between Western medicine (acyclovir, valacyclovir, adenosine cobalamin) and fire needling (risk ratio 1.05, 95% CI 0.98 to 1.12; n = 5). For pain relief (VAS scale): fire needling used alone showed lower scores than Western medicine (SMD -1.37, 95% CI -1.77 to −0.97; n = 2) or external medicine (diclofenac) (SMD-2.23, 95% CI -2.81 to −1.64; n = 1). Combination of fire needling and Western medicine was better than Western medicine alone in relieving pain (VAS scale) (SMD-2.19, 95% CI -3.40 to −0.97, I² = 94%; n = 4). Patients receiving fire needling had lower incidence of neuralgia than those receiving Western medicine (3.3% vs 26.7%, RR 0.09, 95% CI 0.01 to 0.82; n = 1) at follow up for 30 days. No serious adverse events such as infection were reported.

Fire needling appears to offer relief for alleviating pain in herpes zoster. As the sample size of included trials was small and the quality of studies was generally low, rigorous clinical trials with robust reporting and appropriate outcome measures are still needed.