Abstract Traditional Chinese medicine (TCM) needs credible evidence that meets international evidence-based medicine standards to achieve global credibility and acceptance. A fundamental and crucial task is to conduct high-quality randomized controlled trials (RCTs). To achieve global credibility, TCM RCTs should meet universal standards of scientific rigor, such as addressing clinically important questions, achieving sufficient sample size and minimizing risk of bias, and enhance generalizability through appropriate multicenter and pragmatic designs, including Western centers, populations and trialists. In addition, TCM RCTs face unique challenges. Addressing these challenges through rigorous trial methodology and TCM-specific methodological innovation will be essential for establishing globally credible evidence and facilitating the international integration of TCM.
Introduction 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. Methods 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. Results 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. Conclusion 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.
Introduction Anweiyang capsules, a Chinese patent medicine, are used to reinforce qi, resolve toxic substances, and promote healing. In this study, we aimed to conduct the first meta-analysis comprehensively evaluating the clinical effectiveness and safety of Anweiyang capsules combined with Western medicine for the treatment of peptic ulcer disease (PUD). Methods Eight databases were systematically searched up to July 2025 and the further updated to May 1, 2026. The Cochrane risk of bias (ROB) 2.0 tool was used to assess the risk of bias in the included randomized controlled trials (RCTs), and evidence quality was evaluated using the GRADE tool. Results Thirty-six RCTs involving 3858 patients were included. In subgroup meta-analyses based on the background Western medicine regimen, the addition of Anweiyang capsules was associated with a higher clinical effectiveness rate compared with Western medicine alone (standard quadruple therapy: risk ratio [RR] = 1.19, 95% confidence interval [CI]: 1.13, 1.24; standard triple therapy: RR = 1.11, 95% CI: 1.06, 1.16; other regimens: RR = 1.20, 95% CI: 1.16, 1.25). Similar associations were observed for Helicobacter pylori eradication (quadruple: RR = 1.24, 95% CI: 1.17, 1.31; triple: RR = 1.16, 95% CI: 1.10, 1.23; and other: RR = 1.20, 95% CI: 1.13, 1.27). Owing to heterogeneity, gastrointestinal hormones, cytokines, and angiogenic markers were analyzed descriptively, demonstrating reductions in gastrin, motilin, and interleukin-6, along with increased vascular endothelial growth factor levels. Traditional Chinese medicine treatment was also associated with reductions in epigastric pain scores and peptic ulcer recurrence rates. No significant differences in adverse events were observed between the groups. However, most studies showed “some concerns” regarding risk of bias based on ROB 2.0 and low GRADE evidence quality. Conclusion Although this study suggests Anweiyang capsules combined with Western medicine is effective and safe for PUD, further high-quality, large-scale RCTs are warranted for confirmation. Registration: The study protocol was registered with the International Prospective Register of Systematic Reviews (https://www.crd.york.ac.uk/PROSPERO/, CRD420251087273).
Introduction Liuzijue (LZJ), a traditional Chinese exercise, may improve quality of life and pulmonary function in patients with chronic obstructive pulmonary disease (COPD), but evidence for its efficacy and assessment of any subgroup differences remains insufficient. This systematic review of randomized controlled trials (RCTs) evaluated LZJ’s effects on patient outcomes. Methods The Cochrane Library, Web of Science, PubMed, and three Chinese databases were systematically searched from their inception until December 31, 2025. Rigorous screening, assessment of risk of bias, and data extraction were performed in duplicate by two reviewers. A random-effects model with predefined subgroup analyses was used. Statistical significance was set at P < 0.1, and subgroup effect credibility was assessed via a five-criteria checklist. A GRADE evidence profile was established to assess the certainty of evidence. Results We included 24 eligible RCTs comprising 1467 patients. Compared with usual care, the standardized mean difference (SMD) on quality of life in the LZJ group was −0.84 (95% confidence interval [CI]: −1.20, −0.47, P < 0.00001). There were statistical differences for LZJ group for forced expiratory volume in 1 second (FEV1) (mean difference [MD] = 0.28, 95% CI: 0.13, 0.42, P = 0.0002), FEV1% (MD = 5.19, 95% CI: 2.76, 7.62, P < 0.0001), FEV1/forced vital capacity (FVC)% (MD = 6.97, 95% CI: 1.19, 12.75, P = 0.02), and 6-minute walk distance (m) (MD = 33.64, 95% CI: 22.17, 45.10, P < 0.00001). However, no differences were found for FVC (MD = 0.18, 95% CI: −0.06, 0.42, P = 0.14). The certainty of the evidence was low to very low because of the risk of bias, inconsistency, or indirectness. Conclusion Regularly performing LZJ is beneficial for COPD recovery, based on evidence of low to very low certainty. Rigorously designed RCTs that address patient outcomes with longer follow-up periods are required. Registration: This study was registered with PROSPERO (https://www.crd.york.ac.uk/prospero/, CRD42021249739).
The term evidence-based medicine (EBM) was first used in 1991 but its roots began hundreds of years earlier. Over the past 35 years it has evolved considerably into its present-day application. This commentary reviews the history of EBM to the present day, and where the future of EBM may lead over the coming decade. It describes how clinical practice based on personal experience, tradition and anecdotes evidence-based medicine transformed to clinical practice that relies upon a hierarchy of scientific evidence, the comprehensive aggregation and timely access of information and the incorporation of patient values.
Introduction Evaluating complex interventions such as complementary and alternative medicine (CAM), including traditional Chinese medicine (TCM), requires approaches that capture both context and outcomes. Whole-systems research (WSR) employs mixed-methods designs to study these systems in real-world settings. Methods We highlight key methodological considerations for mixed-methods data collection and analysis, illustrated by two case studies: (1) a randomized controlled trial with an embedded process evaluation of spiritual healing for moderate depression; and (2) a cross-sectional survey of oncology providers with written comments (n = 157). Results In Case 1, spiritual healing showed potential benefit for adults with moderate depression. Adherence was high, with minimal dropout and timely questionnaire completion; the process evaluation linked this to close follow-up by the study nurse. In Case 2, communication about CAM differed across provider groups: CAM providers promoted integration with conventional care; physicians were more skeptical, citing limited efficacy evidence; and nurses expressed more positive attitudes. CAM providers and nurses favored strengthening communication between CAM and conventional providers, whereas physicians were less supportive. Qualitative comments enriched and contextualized these patterns. Conclusion Integrating qualitative contextual insights with quantitative outcomes yielded more comprehensive evidence than either method alone, enabling the operationalization of WSR. The detailed procedures for data collection and analysis provide a practical template for students and researchers new to mixed-methods research.
Introduction To quantify the burden of low back pain (LBP) and its risk factors in China from 1990 to 2021 and to assess the efficacy of traditional Chinese medicine (TCM) interventions. Methods The incidence, prevalence, and years lived with disability (YLDs) of LBP in China were searched. Trends from 1990 to 2021 were assessed using estimated annual percentage changes, stratified by age and sex, and joinpoint regression evaluated temporal patterns in LBP burden attributable to risk factors. Then, we searched ten electronic databases (up to April 2025) for randomized controlled trials (RCTs) of TCM interventions. The primary outcomes were pain intensity and physical function. Results In 2021, China had the highest absolute incidence, prevalence, and YLDs of LBP among G20 countries, although its age-standardized YLD rate had decreased significantly since 1990. An estimated 3.31 million YLDs (95% UI: 2.28, 4.53) were attributable to occupational ergonomic factors, 1.85 million (95% UI: 1.08, 2.70) to smoking, and 1.06 million (95% UI: 0.11, 2.23) to high body mass index. The systematic review identified 137 eligible trials involving 11 936 participants. Moderate-confidence evidence showed reduced post-intervention pain intensity with acupuncture plus physiotherapy care (standardized mean difference [SMD] = −1.59, 95% CI [−2.10, −1.09]), acupressure (SMD = −0.87, [−1.17, −0.57]), and acupuncture plus moxibustion (SMD = −2.44, [−2.72, −2.16]) versus physiotherapy care. Improved physical function had moderate-to-very-low confidence with acupuncture (SMD = −1.50, [−2.44, −0.57]) and Tai Chi (SMD = −1.84 [−2.30, −1.37]) compared with physiotherapy care and Western medicine. Conclusion Despite the decline in age-standardized YLD rates since 1990, the absolute burden remains substantial. Incorporating TCM into management may help address this burden but requires risk-stratified, large-scale, high-quality RCTs with extended follow-up. Registration: The study protocol was registered with the International Prospective Register of Systematic Reviews (https://www.crd.york.ac.uk/PROSPERO/, CRD420251054137).
Introduction Although manual therapy, including traditional Chinese tuina and manual physical therapy, is generally effective for knee osteoarthritis (KOA), individual responses vary considerably. This secondary analysis aimed to identify the quantifiable baseline characteristics that predict treatment response, thereby supporting personalized care. Methods Data from a randomized controlled trial comparing tuina and manual physical therapy for KOA were analyzed. At week 4, 59 of 127 patients (46.5%) were responders by Outcome Measures in Rheumatology–Osteoarthritis Research Society International (OMERACT–OARSI) criteria. Candidate variables were screened by univariate analysis (P < 0.25). Multivariate logistic regression identified independent predictors. Internal validation used 1000 bootstrap resamples, with sensitivity analyses including least absolute shrinkage and selection operator (LASSO) and stepwise regression based on Akaike information criterion or Bayesian information criterion. Results Univariate analysis identified disease duration, Kellgren-Lawrence grade, prior treatment satisfaction, all Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) subscales, numeric rating scale (NRS) pain score, 12-item short form health survey (SF-12) mental health score, functional tests, and treatment expectations as associated with response (P < 0.25). Multivariate logistic regression revealed two independent predictors: higher baseline WOMAC pain score (odds ratio [OR] = 1.56, 95% confidence interval [CI]: 1.31, 1.87, P < 0.001) and higher baseline SF-12 mental health score (OR = 1.06, 95% CI: 1.01, 1.12, P = 0.023). The model showed good discrimination (apparent area under the curve [AUC] = 0.838). Internal validation yielded an optimism-corrected AUC of 0.763 and Brier score of 0.169. Calibration and decision curve analyses indicated acceptable fit and net benefit. Conclusion Patients with more severe baseline pain and better mental health are more likely to respond favorably to either tuina or manual physical therapy. These findings bridge pain and mental health as predictors, providing evidence for precision manual therapy in KOA; external validation in larger cohorts is required. Registration: This study was registered with ClinicalTrials.gov (https://clinicaltrials.gov/, NCT03966248).
Introduction Chronic heart failure (CHF) confers high mortality and heavy economic burden as a critical public health issue. Qili Qiangxin (QLQX) capsules, a traditional Chinese patent medicine, may improve clinical outcomes in CHF patients. This study evaluated the economic value of QLQX capsules for CHF. Methods A health economic analysis was performed from the healthcare system perspective. Cost-effectiveness analysis was used for short-term outcomes, and a Markov model-based cost-utility analysis for long-term outcomes. Robustness was tested using one-way and probabilistic sensitivity analyses. Results A total of 1555 patients were equally randomized to two groups: QLQX capsules plus standard of care (QLQX group) or standard of care alone (control group). Baseline characteristics were comparable between groups. In the QLQX group, 1-year direct medical costs were ¥9368.08 ($1311.53; 95% confidence interval [CI]: [¥8980.61, ¥9755.55]), versus ¥6402.21 ($896.31; 95% CI: [¥5903.50, ¥6900.91]) in the control group. The higher costs in the QLQX group were primarily driven by medication expenses. Composite endpoint events occurred in 19.00% (95% CI: [17.07%, 21.03%]) of the QLQX group compared with 23.40% (95% CI: [21.34%, 25.61%]) of the control group (P = 0.003). The incremental cost-effectiveness ratio (ICER) was ¥67 406.14 ($9436.86). Over a 15-year time horizon, the QLQX group incurred total costs of ¥57 096 ($7993.44) and achieved 5.46 QALYs, whereas the control group incurred ¥34 016 ($4762.24) and achieved 5.07 QALYs, resulting in an ICER of ¥58 946 per QALY ($8252.44/QALY). This value is below China’s 2023 per capita gross domestic product threshold (¥89 358; $12 510.12), suggesting that QLQX capsule is highly cost-effective. Sensitivity analyses further confirmed the robustness of these findings. Conclusion QLQX capsules were associated with higher short-term costs but greater efficacy than standard care, and long-term modeling supports their high cost-effectiveness.
This article reviews the newly published book Theory and Methods of Health Technology Assessment in Traditional Chinese Medicine. In response to the mismatch between conventional health technology assessment (HTA) frameworks and the holistic, individualized nature of traditional Chinese medicine (TCM), this book proposes a localized u201CChinese yardsticku201D for evaluation. It integrates standard health economic assessments with TCM-specific characteristics, drawing on over a decade of real-world research on Chinese patent medicines and non-drug therapies. Key innovations include adapting the Population, Intervention, Comparator, Outcome, and Study design (PICOS) framework to incorporate u201Cpattern type,u201D modifying Grading of Recommendations Assessment, Development and Evaluation (GRADE) to account for long-standing clinical wisdom, and employing multi-criteria decision analysis. By bridging the evidence-to-policy gap, the book establishes a scientifically rigorous yet culturally appropriate HTA framework, offering a strategic roadmap for integrating TCM into modern health systems and contributing valuable insights to the global HTA discourse.
Introduction The rapid expansion of systematic reviews (SRs) has led to increasing concerns about research duplication and redundancy. While several tools exist to assess the quality and risk of bias of SRs, no standardized instrument specifically evaluates the degree of duplication between SRs on similar topics. This protocol describes the development and validation of the systematic review duplication (SRD) tool, which is designed to systematically assess and quantify duplication between intervention-based SRs in healthcare. Methods The development process follows established guidelines for creating reporting and quality assessment tools and comprises three phases: (Ⅰ) preparatory work, including team formation and tool conceptualization; (Ⅱ) tool development, involving initial item generation through a systematic literature review and analysis of existing tools, item validation through pilot testing with 40 SRs across 17 disease categories, modified Delphi surveys, and consensus meetings; and (Ⅲ) dissemination through academic channels and professional networks. The SRD tool will evaluate duplication across four domains: research topic, research methods, research results, and research quality. Expert consensus will be achieved through a two-round modified Delphi process with an agreement threshold of at least 70%. Inter-rater reliability will be assessed using the intraclass correlation coefficient and Kendall’s W coefficient. Expected outcomes: The SRD tool is expected to provide a standardized, user-friendly instrument for distinguishing necessary replication from redundant duplication in SRs. It will be available as both web-based and Excel-based applications. Discussion The SRD tool is intended to fill a critical gap in evidence synthesis methodology by enabling the systematic assessment of duplication and supporting informed decision-making by researchers, journal editors, guideline developers, and clinicians.
Introduction 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). Methods 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. Results 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. Conclusions 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.
Introduction Artificial intelligence (AI) is penetrating medical education and its research status needs to be reviewed and suitably integrated. This study aimed to analyze the current status, hotspots, and trends of AI in medical education. Methods Data were retrieved from the Web of Science Core Collection (WOSCC), PubMed, China National Knowledge Infrastructure (CNKI), Wanfang, Chinese Scientific Journal Database (VIP) databases. Using CiteSpace, relevant data were extracted to analyze burst citation detection for keywords, clustering, keyword timelines, and keyword emergence. VOSviewer was used to generate visual collaborative network graphs for the keyword timelines. Results This study identified 2437 published in English and 326 Chinese papers. Cluster analysis identified three core themes: technology-driven medical educational innovation, the intelligent transformation of clinical ability training, and the construction of ethical risk and governance systems. In western research, the focus has been on specific technologies, such as deep learning and robotic surgery, with concentrated ethical discussions emerging in 2022. However, Chinese research is driven by the New Medicine policy, which focuses on the macro-integration of AI and the medical education system, with ethical review mechanisms appearing in clusters in 2024. In general, both Chinese and English articles considered the improvement of practical ability using augmented reality and virtual reality technology and the paradigm shift from knowledge transfer to training in higher-order thinking. Conclusion While specific technologies and earlier ethical debates have been prioritized in English research, policy-driven systemic integration and later governance frameworks have been emphasized in Chinese research, both coverage on enhancing practical abilities and shifting educational paradigms. In future research, AI should be further integrated with medical education values and student-centered innovations should be promoted.
Introduction Myopia is an escalating public health challenge worldwide, with a particularly high burden in China. Although conventional treatments are available, their effectiveness is often limited by issues related to adherence, cost, or safety. Traditional Chinese medicine (TCM), specifically Tuina therapy, offers a preventive approach, with studies suggesting its potential efficacy in the management of pediatric myopia. However, clinical adoption is hindered by lack of standardized treatment protocols. This study aimed to assess the efficacy and safety of Tuina therapy for pediatric myopia and establish a standardized protocol based on the Zhi Wei Bing (prevention first) theory. Methods A multi-method, consensus-based approach was employed, comprising three stages: (i) Problem Identification: Semi-structured expert interviews; (ii) Evidence Retrieval and Synthesis: A systematic literature search (up to September 2023) across Chinese and English databases; and (iii) Recommendation Formulation: A two-round Delphi process, involving 203 ophthalmologists and 76 Tuina specialists, achieved predefined agreement (≥60% consensus) on procedures, acupoint protocols, and TCM pattern differentiation. Recommendations were developed using evidence-to-decision frameworks and Good Practice Statements. Evidence quality and recommendation strength were assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. Results Tuina therapy demonstrated favorable efficacy and safety in the prevention and treatment of low-degree myopia and pseudomyopia in children. A consensus was reached regarding five TCM patterns. A standardized acupoint protocol was established: 14 core acupoints for the preventive stage, 21 for progression management, and 25 for pattern differentiation. A combined strategy using both foundational and pattern-specific acupoints is recommended. The foundational protocol can be applied alone if no specific pattern is identified. Home-based eye exercises were endorsed as complementary strategies. Conclusion This study developed the first evidence-based standardized Tuina protocol for pediatric myopia, addressing a critical gap in non-pharmacological management. These findings suggest that Tuina is an effective and safe therapeutic approach.
Introduction Cancer patients receiving myelosuppressive chemotherapy risk developing chemotherapy-induced pancytopenia (neutropenia, anemia, thrombocytopenia) with possible negative impact on survival due to dose delays or reductions. Moxibustion, the use of heat to stimulate acupuncture points, is a traditional East Asian intervention that may have potential to reduce pancytopenia. This study explored the feasibility of teaching chemotherapy patients in a National Health Service (NHS) cancer center a 10-minute daily intervention. It also aimed to obtain preliminary data to assess the completion of chemotherapy according to both dosage and schedule and assess any reduction of chemotherapy toxicities. Methods This uncontrolled, single-arm study aimed to recruit breast, colorectal or gynecological cancer patients undergoing chemotherapy regimens for which granulocyte-colony stimulating factor (G-CSF) is not indicated. The primary outcome was concordance with daily self-administered moxibustion (starting 7u201210 days before commencing chemotherapy and continuing for three weeks after the final cycle) measured by daily moxibustion diaries. Secondary measures included blood counts, variation to planned chemotherapy schedule, health-related quality of life measured by functional assessment of cancer therapy (FACT)u2013general, FACTu2013anemia, and FACTu2013neutropenia, patient activation measure (PAM-13), chemotherapy-related toxicities, and adverse events of moxibustion. Results Twenty-five participants were recruited. Of a potential 2944 applications, 1369 were recorded; overall concordance rate was 46.5% (individual range 4%u201296%). Main reasons for non-concordance included chemotherapy-related sickness, fatigue, and forgetfulness. There were no serious adverse events. The intervention was acceptable to some patients and oncology healthcare professionals. Challenges to collecting and analyzing data using the outcome measures were identified. Conclusion This was the first known attempt in the West to research using self-applied moxibustion in a conventional cancer care setting. The results indicate this intervention is generally acceptable and that it is possible to recruit to a study. The challenges identified inform recommendations for future study design.
IntroductionDiabetic foot infections impose a substantial economic burden globally, particularly in developing countries such as China. This study evaluated the cost-effectiveness of Fufang Huangbai fluid (FHF) compared with Suprasorb® A + Ag antimicrobial calcium alginate wound dressing (SAAAD) for treating grade 1–2 diabetic foot ulcers (DFUs) (graded according to the International Working Group on the Diabetic Foot/the Infectious Diseases Society of America [IWGDF/IDSA]). MethodsA cost-effectiveness analysis was conducted using 2 weeks of randomized controlled trial data (n = 176) using Chinese healthcare system costs and service fees. Quality-adjusted life years (QALYs) served as the primary health outcome, and costs included drug expenses and dressing services. Both deterministic and probabilistic sensitivity analyses were performed. ResultsCompared with the SAAAD group, the FHF group saved CNY 300.64 and gained an incremental 0.0013 QALYs, making it a dominant approach with a net monetary benefit of CNY 325.86. Sensitivity analysis indicated that the unit price of SAAAD had the greatest impact on the results. At a willingness-to-pay threshold of CNY 20 000 per QALY, the probability of FHF being cost-effective was 70.65%. ConclusionFHF is economically advantageous compared with SAAAD for the treatment of DFUs of IWGDF/IDSA grade 1–2.
IntroductionIn China, improved new drugs with known active ingredients, optimized through a new dosage form, formulation process, or administration route, have attracted increasing attention due to relatively low research and development risks and accelerated regulatory pathways. However, their clinical evidence, regulatory performance, and economic characteristics remain unclear. MethodsWe retrospectively reviewed all improved new drugs (Class 2.2 improved new drugs) approved and marketed in China between January 2020 and September 2025 using data from the YAOZH and Center for Drug Evaluation databases. We evaluated the following characteristics of each product: therapeutic area, dosage-form transition, clinical evidence type (bioequivalence [BE] or non-BE), duration of regulatory review, expedited-pathway designation, and price. Additionally, we identified published clinical trials on products supported by non-BE evidence. Price premiums were calculated as defined daily dose cost differences relative to the earliest marketed formulation of the same active pharmaceutical ingredient and indication. ResultsAcross 14 International Classification of Diseases 11th Revision categories, 71 products (70 chemicals and 1 traditional Chinese medicine) were approved. Overall, 53.5% were approved through BE evidence and 22.5% received priority review. The median review time was 551 days; priority reviews had significantly shorter timelines than standard reviews (374 vs. 582 days; P = 0.00027). Within the priority review cohort, non-BE approvals were non-significantly faster than BE approvals (P = 0.100). Among 30 products eligible for pricing analysis, the median price premium was 91.24% (interquartile range 46.35%–339.05%) relative to the earliest formulations. ConclusionsImproved new drugs represent a pragmatic innovation route that balances development efficiency with regulatory accessibility. For standard reviews, non-BE evidence may facilitate faster approval; further, substantial price premiums were observed and may not consistently align with patient-centered values. Future studies should integrate usability, adherence, safety, real-world outcomes, and pharmacoeconomic evaluations in order to inform value-based reviews and reimbursements.
