OBJECTIVE:Regulatory priorities diverge between agencies - the FDA maintained ACR20 response as primary endpoint in rheumatoid arthritis (RA) trials, whereas the EMA emphasized target-based outcomes. We aim to systematically compare treatment effect estimates between American College of Rheumatology (ACR) response criteria (ACR20/50/70) and target-based outcomes in placebo-controlled trials of approved RA therapies. METHODS:A meta-epidemiological study was performed on randomized placebo-controlled trials investigating approved biological and targeted DMARDs (bioDMARDs and tsDMARDs) in patients with RA. Trials reporting at least one ACR response criterion and one target-based outcome were included. Odds ratios (ORs) for each outcome were computed, followed by calculation of a risk of odds ratio (ROR) to quantify differences in treatment effects between ACR and target-based outcomes. The primary outcome was the treatment effect differences between ACR20 and target-based efficacy estimates, and the second outcome was to explore which alternative ACR response criteria were concordant with target-based outcomes. RESULTS:A total of 53 RCTs (392 study arms) involving 30,778 RA patients were analyzed. Trials using ACR20 demonstrated significantly greater treatment effect estimates compared to those using remission outcomes (ROR = 0.65, 95% CI 0.52-0.81) and LDA outcomes (ROR = 0.78, 95% CI 0.69-0.89). Higher ACR thresholds (ACR50 and ACR70) showed better consistency with target-based outcomes, with ACR70 aligning with remission (ROR = 0.88, 95% CI 0.76-1.01) and ACR50 aligning with LDA (ROR = 0.95, 95% CI 0.81-1.11). Subgroup analyses indicated that the discordance between ACR20 and target-based outcomes persisted across different intervention drugs, comparison types, and previous treatments. CONCLUSION:ACR20 overestimates treatment effects relative to target-based outcomes, while ACR50/70 demonstrate better concordance. Harmonizing endpoints by integrating more stringent ACR response or co-primary endpoints (ACR response criteria + target-based outcomes) could bridge regulatory discrepancies and enhance clinical relevance in RA drug development.

Background:China's transition toward people-centered health governance has highlighted the essential role of pharmacists in ensuring rational medication use and protecting public health. However, pharmacists' professional roles remain fragmented across institutional, social, and regulatory dimensions. Drawing on public value theory, this study examines the structural and cognitive misalignments constraining pharmacist professionalisation in China and situates these challenges within an international context. Methods:This study employed a literature-based conceptual analysis informed by public value theory. National laws, administrative regulations, policy documents, and scholarly studies were reviewed to examine how public value - specifically value consensus, legitimacy and support, and operational capacity - is reflected in pharmacist governance. Evidence from existing empirical studies was integrated to illustrate gaps in public cognition, administrative coordination, and professional self-identity, with their scope and limitations qualitatively appraised. Results:Three interrelated challenges were identified. First, fragmented administrative governance across regulatory bodies leads to inconsistent legal definitions, unclear role boundaries, and limited institutional authority for pharmacists, particularly in clinical decision-making and medication therapy management. Second, public awareness of pharmacists' professional value is insufficient; survey evidence indicates that patients largely associate pharmacists with dispensing or sales functions, leading to low social demand for pharmaceutical care and inadequate legitimacy for role expansion. Third, pharmacists demonstrate inconsistent professional self-identification: many hospital pharmacists prioritise logistical tasks, while most community pharmacists remain oriented toward commercial rather than patient-centered service roles. Together, these structural, cognitive, and professional gaps undermine value consensus, legitimacy, and operational capacity within the pharmacist ecosystem. Conclusion:Advancing pharmacist professionalisation in China requires integrated legislation and cross-sectoral governance, enhanced public communication and health literacy, and strengthened professional competencies supported by adequate incentives. These findings echo international experiences, highlighting pharmacist professionalisation as a shared global governance challenge rather than a China-specific issue.

Fluoropyrimidines are a vital component of chemotherapy regimens. Deleterious DPYD variants reduce activity of dihydropyrimidine dehydrogenase, the rate-limiting enzyme of fluoropyrimidine catabolism, resulting in reduced fluoropyrimidine clearance and elevated risk of life-threatening toxicities. DPYD genotype-guided fluoropyrimidine therapy can mitigate the risk of severe life-threatening toxicities, but adoption of testing globally has been limited. We developed a 91-item survey investigating global DPYD implementation strategies to gain insight into common practices and successful strategies. The survey was disseminated to Pharmacogenomics Global Research Network Implementation Working Group members consisting of 54 health care sites across 15 countries. Survey responses were received from 28 sites (52%) across 9 countries. Over 80% of sites implemented, or planned to implement, a preemptive testing strategy (i.e., before a fluoropyrimidine is administered) leveraging the electronic health record (EHR) to disseminate DPYD results to providers. All sites created infrastructure to support DPYD testing (e.g., order sets, EHR decision support), but 70% of sites indicated reliance on clinicians to remember test ordering. Only 2 sites reported high DPYD testing rates (> 75%) among patients planned to receive a fluoropyrimidine. Most sites (57%) used in-house clinical laboratories that tested for the majority of DPYD Tier 1 variants. Among sites that had implemented DPYD testing, the median turnaround time was 10 days. Few sites indicated that a high percentage (> 75%) of DPYD results were returned before fluoropyrimidine administration. Our results suggest that additional implementation strategies are needed, addressing barriers and facilitators of DPYD testing.

Background: Precision oncology drugs are a class of targeted drugs that are most effective in a molecularly defined subset of cancer patients. Pretreatment molecular profiling is integral to optimal patient selection. However, discordances between molecular profiling results and actual drug selection become evident in clinical practice. This study aimed to assess the discordances between molecular alterations and actual drug selection of non-small cell lung cancer (NSCLC) in China. Methods: This retrospective cohort study consecutively included NSCLC patients from a specialized oncology hospital and a general hospital in Beijing between November 2021 and June 2022. Discordances between molecular profiling results and first-line drug selection consisted of the following four scenarios: (1) not receiving any drugs after molecular profiling; (2) receiving precision oncology drugs before getting molecular profiling results or without molecular profiling results; (3) receiving precision oncology drugs without any targeted gene mutations; (4) not receiving precision oncology drugs with targeted gene mutation. Primary outcome was the proportion of discordances of included NSCLC patients in China. Secondary outcomes were the proportion of four scenarios of discordances. Findings: A total of 707 NSCLC patients were included, of whom 519 were diagnosed with adenocarcinoma, 172 with squamous cell carcinoma, and 16 with other pathological types. The proportion of molecular profiling in NSCLC patients was 62.4% (441/707), with adenocarcinoma patients accounting for the highest percentage at 83.4% (368/441). The proportion of discordances between molecular profiling results and first-line drug selection was 25.2% (178/707). 17.8% (126/707) patients did not receive any drugs after molecular profiling, 1.7% (12/707) received precision oncology drugs before getting molecular profiling results or without any molecular profiling results, 1.1% (8/707) received precision oncology drugs without any targeted gene mutations, 4.5% (32/707) did not received precision oncology drugs with targeted gene mutation. Interpretation: This study highlighted a quarter of NSCLC patients had the discordances between molecular profiling results and first-line drug selection in China, which may result in a loss of survival benefit to the patient, and a waste of the value of molecular profiling. Future studies need to evaluate and intervene the discordances to optimize the implementation of precision oncology therapy.

To examine the prevalence of treatment indications for antidepressants and assessed temporal trends in antidepressant prescribing for depression among adult patients in primary health care facilities (PHFs) in China. Descriptive study of antidepressant prescriptions written by primary care physicians. Setting participants: Patients aged 18 years and above in 67 PHFs in Dongcheng district in Beijing between 1 January 2014 and 31 December 2022. Deidentified information including patient demographics,antidepressants prescribed,and corresponding diagnoses were extracted from the prescribing system. The primary outcome was the treatment indications for all antidepressants prescribed between 2014 and 2022. Prescriptions were classified as on-label or off-label depending on whether the drug was approved for the indication by China's National Medical Products Administration by September 2022. A total of 42379 antidepressant prescriptions were identified between 2014 and 2022. Only 21.21 % of antidepressant prescriptions were indicated for depression. Anxiety disorders (31.43 %), insomnia (20.07 %), pain(19.12 %) and digestive system disorders (16.34 %) are also frequently prescribed antidepressants by physicians. For these indications, the most frequently prescribed antidepressant was flupentixol/melitracen and sertraline.For 36.32 % of all antidepressant prescriptions,physicians prescribed a drug for an off-label indication,especially insomnia and pain.Physicians also prescribed antidepressants for several indications that were off-label for all antidepressants, including digestive system disorders and migraine. This study found compound antidepressants are widely prescribed and used off-label indications.There is a need for more evidence to evaluate the clinical outcomes associated with off-label antidepressant indications for older adults to optimise prescribing decisions at PHFs.

BACKGROUND:Pharmacogenetic testing offers a pathway to safer prescribing and improved outcomes in older adults, who face heightened risks of adverse drug reactions due to polypharmacy and age-related metabolic changes. This study evaluates the prevalence of actionable pharmacogenetic biomarker use and estimates the potential impact of genotype-guided dosing in Chinese older adults. METHODS:This retrospective cross-sectional analysis utilized 2015-2017 claims data from the China Health Insurance Research Association (CHIRA), encompassing 3,309,025 older patients (≥ 65 years) and 74,415,484 prescriptions. Drugs with Clinical Pharmacogenomics Implementation Consortium (CPIC) Level A evidence for actionable pharmacogenetic variants (n = 53) were identified. Key measures included the prescribing prevalence of Level A drugs and projected rates of actionable phenotype-driven dosing changes, calculated using population-specific genotype frequencies from PharmGKB and published sources. RESULTS:Among older adults, 43.4% (433.8 per 1000) were prescribed ≥ 1 CPIC Level A drug. Atorvastatin (131.1 per 1000), omeprazole (124.3 per 1000), and clopidogrel (75.7 per 1000) were the most common. Over one-third (36.5%; 365.3 per 1000) of exposures required genotype-guided dose adjustments, with clopidogrel (CYP2C19) and statins (SLCO1B1) representing the highest-priority gene-drug interactions (259.6 and 221.8 per 1000, respectively). CONCLUSIONS:CPIC Level A pharmacogenetic biomarkers are prevalent in Chinese older adults, with over 40% exposed to actionable gene-drug pairs and 36.5% requiring dose adjustments. These findings highlight the clinical imperative to integrate pharmacogenetic testing into geriatric care, prioritize CYP2C19 and SLCO1B1 testing, and develop region-specific guidelines to mitigate polypharmacy risks. Policymakers and clinicians should consider targeted implementation strategies to optimize prescribing safety and efficacy in aging populations.

Objectives: This study aimed to use Bayesian network meta-analysis to compare the efficacy and safety of biologics for systemic lupus erythematosus (SLE). A comprehensive and systematic search of electronic databases (PubMed, Medline, Cochrane Library, EMBASE, Web of Science, CNKI, and WanFang Data) was conducted from 2014 to September 2024. Our study only included randomized controlled trials with full articles that enrolled adult SLE patients treated with biologics, in comparison with standard therapy. The primary efficacy endpoints were SLE Responder Index 4 (SRI4) and BICLA (BILAG-Based Composite Lupus Assessment). The safety endpoints were adverse events (AEs) and serious adverse events (SAEs). R 4.4.3 and RStudio were used to conduct the network meta-analysis. RevMan 5.4 was used to assess the included literature. 29 randomized controlled trials with a total of 13,712 patients met the inclusion criteria. The network meta-analysis indicated that compared with standard therapy, telitacicept (OR 5.2, 95

To the editor: Using drugs off-label in paediatric patients(age:0-18 years)has drawn increasing attention worldwide.Off-label use of drugs implies using drugs beyond the scope of their approved market authorisation(eg,patient age,indication,dosage and route of adminis-tration).Previous literature reported that the prevalence of off-label drug use ranged from 36.3％to 97.0％among paediatric patients worldwide.1 Off-label medicinal use is a poten-tial risk factor for adverse drug reactions2 3 and may increase the risk of ineffective treat-ment.4 The US Food and Drug Administra-tion(FDA)has enacted numerous laws and policies to incentivise or mandate that phar-maceutical companies consider and conduct paediatric clinical trials.Nonetheless,approx-imately three-fourths of prescribed drugs in the USA have not been assessed in the paedi-atric population.5

Background There is a disconnection between the continued pressing clinical demand for rheumatoid arthritis (RA) treatments and the saturation of the current therapeutic markets. The design of rheumatoid arthritis trials might represent one of significant barrier to advancing therapeutic progress. A comprehensive review was performed to evaluate the characteristics of RA trials registered in ClinicalTrials.gov from 2013 to 2023. Methods The ClinicalTrials.gov database was searched for trials focused on the RA interventional trials from 2013 to 2023. Interventional drug or biological trials were included. Key characteristics of RA trials were summarized and target population, control groups selection, and clinical endpoints were evaluated. Results Between January 2013 and December 2023, 425 RA trials were included. Decreased trial numbers, excessive industry sponsorship, and delayed published results were found. For target population, 28% clinical trials didn’t define distinct RA patients, and 38% of the trials included population with no upper age limit. For control groups, only 36% trials had head-to-head comparisons, 50% were placebo-controlled, where half of placebo-controlled trials were with special design (add-on, early escape, double dummy), and half without any design. For clinical endpoints, ACR20 (24%) and DAS28 (21%) were the most commonly used outcomes, with declining ACR20 and ascending DAS28. Only 7% trials adherence to “treat-to-target” strategy, but the most commonly used outcome measures not aligned with guideline-recommended. Conclusions Our study contributes to a nuanced comprehension of the current landscape of RA trials and offers valuable insights for future improvement. This included the necessity of stratifying the target population based on disease activity or treatment history to achieve precision in treatment; considerations of more stringent or sensitive clinical endpoints to provide better discriminatory power; addressing discrepancies between the endpoints selected for treat-to-target and those recommended by guidelines to choose optimal treatment strategy.

Purpose Patients with coronary artery disease (CAD) need to take antiplatelet drugs regularly in order to prevent thrombosis; however, there is existing inter-individual variability in drug response. Pharmacogenomic studies indicate that drug response may also be influenced by genetic variants, and multiple genetic variants may work together. We assumed that patients carrying more risk alleles might have a worse clopidogrel drug response and that a polygenic model integrated different single variants might have the potential to explain clopidogrel drug response variability better. We aimed to investigate whether the polygenic model could be used to predict clopidogrel drug response. Methods A total of 935 CAD patients were enrolled in the study. We investigated the association between 19 clopidogrel-related single-nucleotide polymorphisms (SNPs) and the incidence of recurrent ischemic events. Additionally, a polygenic model was constructed to assess the risk of ischemic events. Findings There were only 2 SNPs of CYP2C8 gene (rs1934980 and rs17110453) that were nominally associated with incidence of recurrent ischemic events. We constructed a polygenic model integrated with 6 clopidogrel-related SNPs. When compared with patients carrying 6 or fewer risk alleles, patients with 7 or more risk alleles had a higher risk of ischemic events (hazard ratio = 1.87; P = 0.04). Implications The polygenetic model may be useful for clopidogrel drug response prediction in patients with CAD.

Background: Promoting the use of generic drugs is a viable strategy to control drug costs. As physicians have a critical role in deciding on what drugs to prescribe and thus whether certified generic drugs were actually used, this study aimed to analyze factors influencing whether physicians were willing to prescribe generic drugs versus brand-name drugs after the implementation of Consistency Evaluation Policy (CEP). Methods: A discrete choice experiment (DCE) was developed to explore factors influencing physicians’ preferences toward prescribing brand-name drugs versus its certified generic. There were four attributes in the model, namely prices, hospital-level cost control measures, information about clinical safety and efficacy of generic drugs, and reimbursement rate. In total, 1297 physicians from 101 hospitals participated in the study and 1047 questionnaires were retained. Results: We found that substantial disclosed information about the generic’s clinical safety and efficacy (Sufficient information, odds ratio [OR]=3.251, 95% CI=3.098-3.412), lower price of the certified generic (price ratio of generic drugs versus brand-name drugs=1: 10, OR=1.130, 95% CI=1.078-1.185), stringent hospital cost control measures (the brand-name drugs were affected by the national centralized drug procurement (NCDP) policy or a tight cost-control measure, OR=1.247, 95% CI=1.190-1.307), and lower reimbursement rates for brand-name drugs (reimbursement rate=20%, OR=1.283, 95% CI=1.224-1.346) all increased physicians’ propensity to prescribe certified generic drugs. Conclusion: When certified generic drugs were lower priced or disclosed more information about their clinical safety and efficacy or when brand-name drugs were subject to tighter hospital cost control measures, physicians were more inclined to prescribe certified generic drugs. The findings suggest that CEP, together with the NCDP to promote market competition and hospital cost control measures targeting brand-name drugs, promoted the use of generic drugs through influencing physician prescribing behavior. The widely use of generic drugs may further benefit from increased disclosure of the clinical safety and efficacy of generic drugs by their manufacturers.

Background: Although affordable generics could probably contribute to the solution of rapidly increasing pharmaceutical expenditure, those drugs are prescribed at a lower rate in China. Physicians' perception and knowledge of generics have a great influence on their prescribing behavior. Objective: This study aimed to identify factors that affect physicians' generic prescribing behavior based on the theory of planned Methods: Data were collected by both electronic and paper-based surveys from 1297 Chinese physicians, and 1047 surveys were retained. The structural equation model (SEM) was employed to investigate the relationship between four behavioral constructs, namely, attitudes, subjective norms, perceived control of behaviors, and intentions. Results: About 50% of Chinese physicians had a positive attitude towards generic drugs that had passed the "Consistency Evaluation of Quality and Efficacy of Generic Drugs" (high-quality generic drugs), but their knowledge of generic drugs was relatively inadequate. The path coefficients for the effect of attitudes, subjective norms, and perceived behavioral control on behavioral intention were 0.285, 0.366, and 0.322 respectively. The path coefficients for the effect of behavioral intention and perceived behavioral control on prescribing behavior were 0.009 and 0.410 respectively. Conclusion: Physicians' attitudes, subjective norms, and perceived behavioral control were significant positive correlation predictors of behavioral intention. Subjective norms and perceived behavior control had a greater impact than attitude on physicians' prescribing intention. However, the generic prescribing behavior is not under the volitional control of Chinese physicians. Physicians' prescribing practice is likely affected by perceived strong control over prescribing generic drugs.

Although several case reports and small clinical trials have reported promising outcomes with Janus kinase (JAK) inhibitors for vitiligo, high-quality evidence and guidelines are lacking. We evaluated the efficacy and safety of JAK inhibitors for the treatment of vitiligo using a meta-analysis of randomized controlled trials (RCTs). We searched the PubMed, Embase, and Cochrane Library databases up to August 2023, with additional studies from ClinicalTrials.gov and company websites. We assessed outcomes, including percentage improvement in total vitiligo area score index (TVASI) and facial vitiligo area score index (FVASI); the proportion of patients achieving 50% improvement in TVASI (TVASI50) and 50% and 75% improvement in FVASI (FVASI50 and FVASI75); the risk of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), infections, and skin-related adverse events (AEs). Five studies with 1,550 participants were included. JAK inhibitors were associated with a higher proportion of TVASI50 (relative risk [RR] 2.67, 95% confidence interval [CI] 1.24-5.78) and FVASI75 (RR 3.97, 95%CI 2.62-6.02) responders than placebo. JAK inhibitors significantly increased the risk of skin-related AEs (RR 1.96, 95% CI 1.29-2.98) compared with placebo. However, the risk of TEAEs, SAEs, and infections was not significantly different between the JAK inhibitor and placebo groups. Subgroup analysis showed that JAK1 and JAK1/2 inhibitors were more effective than JAK3 inhibitors. However, there was insufficient evidence to suggest that the route of administration affects the efficacy and safety of JAK inhibitors in vitiligo. These findings indicate that JAK inhibitors are effective in repigmentation and well tolerated in patients with vitiligo.

With the premise of drug safety and effectiveness, pharmacoeconomic evaluation can provide optimal solutions for diversified decision-making application scenarios from different research perspectives while maximizing the rational utilization of existing healthcare resources. Chinese patent medicine is an essential component of pharmaceutical utilization in China and a significant part of healthcare expenditure in China. However, the economic evaluation of post-marketing Chinese patent medicine is lacking. These evaluations often lack standardization, exhibit varying quality, and are unable to effectively support healthcare decisions, indicating a need for improvement in overall quality. Given this situation, this project has gathered leading experts from China and has strictly adhered to the requirements of the group standards set by the China Association of Traditional Chinese Medicine in developing Guidelines for economic evaluation of post-marketing Chinese patent medicine, aiming to provide methodological guidance for the post-market pharmacoeconomic evaluation of Chinese patent medicine, enhancing the standardization of pharmacoeconomic evaluations of Chinese patent medicine and the scientific validity of research results, and thereby elevating the overall quality of pharmacoeconomic evaluations for post-marketing Chinese patent medicine. The guidelines adhere to the framework provided by relevant laws and regulations in China and technical guidance documents. It is based on guidance from traditional Chinese medicine(TCM) theories, focusing on the unique characteristics of TCM. It covers various aspects of pharmacoeconomic evaluation, including fundamental principles, research topic selection, research question definition, study design type selection, cost identification and measurement, health outcomes, and evaluation methods. The guidelines offer methodological recommendations and decision guidance to address common issues and challenges in the pharmacoeconomic evaluation of post-marketing Chinese patent medicine.