方法与临床研究雷达（2026-08-25）
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1. Social Cognition as an Under-Used Behavioural Endpoint in Neurodevelopmental Psychopharmacology: A Conditional Framework for Integrating Theory of Mind into Clinical Trial Design.
主题：临床试验方法与统计实践
相关性分数：6
期刊：European journal of pharmacology
公开日期：2026-08-20（电子公开）
期刊卷期日期：2026-Aug-20
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
Social cognition, encompassing theory of mind (ToM), facial affect recognition, and mentalising under social load, is impaired across several neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), developmental language disorder (DLD), and intellectual disability (ID). These impairments are plausibly downstream of neurochemical processes, particularly serotonergic, dopaminergic, neuropeptidergic, and excitatory-inhibitory modulation of prefrontal-temporal-limbic circuits, although this pathway is indirect and moderated by age, language, cognitive ability, and comorbidity. Despite this, performance-based social cognition is rarely positioned as a primary or co-primary endpoint in NDD pharmacotherapy trials. The predominant standard, the Aberrant Behavior Checklist Irritability subscale and its caregiver-rated relatives, indexes reactive behavioural output that may be construct-distant from the mechanisms through which several contemporary agents are hypothesised to act. This narrative review advances a conditional thesis: endpoint-mechanism misalignment is one plausible contributor to the uninterpretability of certain null trials, alongside insufficient power, sample heterogeneity, unverified target engagement, dosing limitations, high placebo response, and genuine inefficacy. We synthesise condition-specific social-cognitive profiles with graded evidence, the neurobiological substrates across mechanism classes, and a three-tier framework positioning social cognition as a co-primary endpoint for mechanism-matched agents and as a prespecified secondary or moderator variable otherwise. We set out the measurement and regulatory preconditions fit-for-purpose validation, adequate test-retest reliability, practice-effect control, and defined meaningful change that must precede such repositioning. We do not claim ToM should replace existing endpoints or that it suits all NDD trials.
2. Application of competing risks models in cardiovascular mortality research: findings from the Tehran lipid and glucose study.
主题：生存与复杂事件结局方法
相关性分数：6
期刊：Journal of diabetes and metabolic disorders
公开日期：2026-07-21（电子公开）
期刊卷期日期：2026-Dec
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
PURPOSE: Cardiovascular diseases (CVD) are a leading cause of mortality in Iran and globally. This study aimed to provide more accurate estimates of associations between risk factors and CVD mortality by applying competing risk models within the Tehran Lipid and Glucose Study cohort.
METHODS: In this prospective analysis, 7,529 individuals aged ≥ 30 years without prevalent CVD were followed for a median of 19.87 years. The primary outcome was CVD mortality (n = 311), with non-CVD death as the competing event (n = 592). Analyses were stratified by sex and age (< 65 vs. ≥65 years). Cause-specific and Fine-Gray models estimated hazard ratios for diabetes, hypertension, hypercholesterolemia, smoking, and body mass index.
RESULTS: Diabetes and hypertension were the strongest predictors of CVD mortality across most subgroups. In the Fine-Gray model, diabetes showed the greatest impact in women < 65 years (HR: 4.83, p < 0.001), while hypertension showed the strongest association in women ≥ 65 years (HR: 3.32, p < 0.001). Hypercholesterolemia was associated with increased CVD mortality exclusively in women < 65 years (HR: 1.79, p = 0.02). Body mass index showed no significant association.
CONCLUSION: Diabetes and hypertension are the predominant risk factors for CVD mortality in the presence of competing risks, with effect magnitudes varying by sex and age. Applying competing risk models is essential for accurate risk estimation and targeted prevention in populations with high competing mortality burden.
3. A pragmatic randomized trial to evaluate the vaccine effectiveness of bivalent RSV prefusion F vaccine for preventing RSV hospitalizations in adults (DAN-RSV): Trial design update.
主题：临床试验方法与统计实践
相关性分数：6
期刊：American heart journal
公开日期：2026-06-01（电子公开）
期刊卷期日期：2026-Oct
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of respiratory morbidity in adults, particularly among older individuals and those with comorbidities. The DAN-RSV trial was initiated to evaluate bivalent RSV prefusion F (RSVpreF) vaccine effectiveness in preventing RSV-related hospitalizations.
METHODS: DAN-RSV is a large-scale, pragmatic, randomized clinical trial that enrolled participants during the 2024/2025 (Danish adults aged ≥60 years) and 2025/2026 (adults aged ≥18 years in Denmark and Galicia, Spain) Northern hemisphere winter seasons. In Denmark, nationwide registries and the national electronic messaging system were used to identify and recruit eligible citizens; individuals could provide electronic informed consent remotely or in-person. In Galicia, participants were recruited via text message invitations and consented on-site.
RESULTS: During the initial 2024/2025 season, 131,379 Danish adults aged ≥60 years were enrolled. Following lower-than-expected event accrual and expansion of the EU indication to adults 18 years and older, the trial was extended to continue enrollment of adults aged ≥18 years across Denmark and Galicia, Spain during the 2025/2026 RSV season. Key protocol updates include expansion of the eligibility criteria to adults aged ≥18 years, inclusion of an additional study site within the integrated public healthcare infrastructure of Galicia, Spain, and an increase in the planned sample size to up to approximately 690,000 participants across both seasons. The randomization strategy (1:1 to RSVpreF vaccine or no vaccine), primary endpoint (RSV-related respiratory tract disease hospitalization), and statistical framework, including intention-to-treat analyses and hierarchical testing, remain unchanged.
CONCLUSION: The extension of the DAN-RSV trial is expected to improve statistical precision, enhance generalizability, and strengthen the robustness of the effect estimates. The updated design will provide reliable randomized evidence on bivalent RSVpreF vaccine effectiveness to inform clinical and public health decision-making.
4. Concurrent chemotherapy and external radiation therapy (ConCERT): phase 3 noninferiority randomized clinical trial of cisplatin weekly vs every 3 weeks in locally advanced squamous cell carcinoma of the head and neck.
主题：临床试验方法与统计实践
相关性分数：5
期刊：Journal of the National Cancer Institute
公开日期：2026-08-24（电子公开）
期刊卷期日期：2026-Aug-24
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
INTRODUCTION: Concurrent chemoradiotherapy with cisplatin (100 mg/m² every three weeks) is the standard for locally advanced head and neck squamous cell carcinoma (LA-HNSCC), but it is uncertain if weekly cisplatin (40 mg/m²) is non-inferior.
METHOD: This open-label, multicentre, phase III non-inferiority trial randomised patients with non-nasopharyngeal LA-HNSCC in a ratio of 1 1 to receive either the standard cisplatin regimen (100 mg/m² every three weeks) or the experimental weekly regimen (40 mg/m²), both with 70 Gy concurrent radiation. The primary endpoint was 2-year locoregional control (LRC) and non-inferiority margin was kept as 10% (-10%).
RESULTS: From April 2018-January 2021, 278 patients were enrolled (137 standard and 141 experimental arm); 272 were eligible for final analysis. Median follow-up was 43.9 months. Two-year LRC rates were 61.3% (experimental arm) and 51.1% (standard arm) with an absolute difference of 10.2% (one-sided 95% CI 0.3), within the non-inferiority margin. Hazard ratio was 0.72 (95% CI: 0.50 to 1.05, P = 0.091). Kaplan-Meier analysis also confirmed non-inferiority (absolute difference 10.8%). Median progression-free survival was 17.9 months (standard) and 20.3 months (experimental) (P = 0.204); median overall survival was 22.2 months (standard) and 24.9 months (experimental) (P = 0.501). Grade 3 or higher adverse events occurred more in the standard arm (60.7% vs 44.7%, P = 0.018), as did hospitalisations (36.8% vs 20.3%, P = 0.004).
CONCLUSION: Weekly low-dose cisplatin-based chemoradiation is non-inferior to 3-weekly high-dose cisplatin and is associated with lower toxicity and fewer hospitalisations, making it a viable treatment option for non-nasopharyngeal LA-HNSCC.
5. Cost-effectiveness of perioperative pembrolizumab plus enfortumab vedotin for cisplatin-ineligible or cisplatin-declining patients with muscle-invasive bladder cancer in the United States.
主题：因果推断、RWE 与卫生经济学
相关性分数：5
期刊：Journal of medical economics
公开日期：2026-08-18（电子公开）
期刊卷期日期：2026-Dec
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
AIMS: In the KEYNOTE 905/EV 303 study, perioperative enfortumab vedotin plus pembrolizumab (EV+Pem) improved event-free survival (EFS), overall survival (OS), and pathological complete response in a predominantly cisplatin-ineligible muscle-invasive bladder cancer (MIBC) population, compared with surgery alone with or without adjuvant nivolumab, as indicated (surgery ± adjuvant nivolumab). This study assessed the cost-effectiveness of perioperative EV+Pem for cisplatin-ineligible or declining patients with MIBC from a US third-party payer perspective.
METHODS: This cost-utility analysis used a state-transition Markov model with event-free (EF), progressed or recurrent disease (PRD), and death health states. The target population included cisplatin-ineligible or cisplatin-declining adults with MIBC. Transitions from EF were estimated using parametric multistate survival models based on trial data, with extrapolation beyond follow-up. Survival following PRD was modeled using a treatment-mix approach reflecting US clinical practice. Costs were derived from US sources, and utilities from KEYNOTE-905 EQ-5D-5L data. Scenario analyses explored alternative extrapolations and structural assumptions, and sensitivity analyses assessed parameter uncertainty.
RESULTS: In the base case, EV+Pem increased life-years by 3.08 (7.70 vs 4.62) and quality-adjusted life-years (QALYs) by 2.56 (6.19 vs 3.62) versus surgery ± adjuvant nivolumab. EV+Pem was associated with higher initial treatment costs, increasing total costs by $133,661 ($546,831 vs $413,171), partially offset by lower costs of treatment for PRD ($34,636 vs $129,813), yielding an incremental cost-effectiveness ratio (ICER) of $52,117 per QALY gained. Across scenario analyses, ICERs ranged from $50,363 to $69,703 per QALY gained. Probabilistic sensitivity analysis showed that EV+Pem had a 99.1% probability of being cost-effective at a $100,000 per QALY threshold.
LIMITATIONS: Results are subject to uncertainty in long-term survival extrapolation and evolving treatment patterns following PRD.
CONCLUSIONS: EV+Pem is cost-effective versus surgery ± adjuvant nivolumab for cisplatin-ineligible or cisplatin-declining patients with MIBC from a US third-party payer perspective at a willingness-to-pay threshold of $100,000 per QALY.
6. Cost-effectiveness analysis of finotonlimab in the treatment of advanced recurrent metastatic head and neck squamous cell carcinoma in China.
主题：因果推断、RWE 与卫生经济学
相关性分数：5
期刊：Human vaccines & immunotherapeutics
公开日期：2026-08-10（电子公开）
期刊卷期日期：2026-Dec
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
The SCT-I10A-B301 trial demonstrated efficacy and safety of finotonlimab combined with chemotherapy in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, the economics of this therapy are unknown. This study aims to assess the cost-effectiveness of incorporating finotonlimab into chemotherapy regimens for R/M HNSCC from the viewpoint of the Chinese healthcare system. A Markov model was developed to evaluate the treatment costs and outcomes of finotonlimab combined with chemotherapy for R/M HNSCC. Survival data were obtained from the SCT-I10A-B301 trial. Considering only direct medical costs, survival data, and utilities. The principal result measures employed were the incremental cost-effectiveness ratio (ICER). To identify how parameter uncertainty affected the model, one-way sensitivity analyses, probabilistic sensitivity analysis (PSA), and scenario studies were carried out. The results showed that the financial burden of finotonlimab, when administered concomitantly with chemotherapy ($36,996.99) was $26,072.18 higher than chemotherapy ($10,924.81) but also increased by 0.23QALY (0.89QALY vs. 0.66QALY), with an ICER of $112,384.47/QALY, which was higher than the willingness to pay (WTP) of $40,744/QALY. The model’s sensitivity to three factors was particularly pronounced: the utility of PFS, the utility of PD, and the cost of finotonlimab. Scenario analysis showed that a price reduction for finotonlimab could significantly reduce the ICER to near the WTP threshold. Compared with chemotherapy alone, finotonlimab combined with chemotherapy has been determined to be an ineffective, cost-effective therapeutic strategy for the first-line medical treatment of R/M HNSCC in China, and the price discount of finotonlimab can improve its cost-effectiveness.
7. Cost-effectiveness of pembrolizumab as neoadjuvant therapy and in combination with standard of care (SOC) as adjuvant therapy for stage III-IVA resectable locally advanced head and neck squamous cell carcinoma (LA HNSCC) in Switzerland.
主题：因果推断、RWE 与卫生经济学
相关性分数：5
期刊：Journal of medical economics
公开日期：2026-08-07（电子公开）
期刊卷期日期：2026-Dec
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
AIMS: KEYNOTE-689 trial results demonstrated that neoadjuvant pembrolizumab followed by adjuvant pembrolizumab plus standard of care (NP/AP + SOC) significantly improved event-free survival (EFS) versus SOC alone in patients with locoregionally advanced head and neck squamous cell carcinoma (LA HNSCC). This study evaluated the cost-effectiveness of NP/AP + SOC vs. SOC from the Swiss healthcare perspective.
MATERIALS AND METHODS: A 4 mutually exclusive health state US-specific Markov cohort model was adapted to the Swiss healthcare perspective. Efficacy inputs were derived from patient-level KEYNOTE-689 data using parametric survival analysis. Healthcare resource utilisation and costs (2025 Swiss Franc [CHF]) were obtained from Swiss clinical experts and national tariffs. Health state utilities were derived from EuroQoL-5 dimension data collected in KEYNOTE-689. Outcomes included costs, quality-adjusted life-years (QALYs) and life-years (LYs), measured over a lifetime horizon. At the base-case, a 3.0% discount rate was applied to costs and effectiveness. Cost-effectiveness was evaluated as an incremental cost-effectiveness ratio (ICER) at a hypothetical willingness-to-pay (WTP) threshold of CHF 100,000/QALY gained. Deterministic, probabilistic, and scenario analyses were conducted for sensitivity.
RESULTS: NP/AP + SOC treatment extended life expectancy by 1.81 years compared to SOC, generating 1.42 incremental QALYs. Total costs were CHF 172,086 for NP/AP + SOC versus CHF 151,908 for SOC, resulting in incremental costs of CHF 20,178/patient. ICERs were CHF 14,227/QALY gained and CHF 11,130/LY gained. At a WTP of CHF 100,000/QALY gained, NP/AP + SOC had a 96% probability of being cost-effective.
LIMITATIONS: Long-term follow-up data (median 3.2 years) required extrapolation; real-world Swiss cost data were unavailable necessitating expert opinion; Belgian utility values were used as Swiss-specific data were unavailable.
CONCLUSION: NP/AP + SOC is cost-effective for LA HNSCC in Switzerland, supporting clinical implementation.
8. Real-world evidence on off-label underdosing of direct oral anticoagulants in Asian patients with atrial fibrillation: prescribing patterns, determinants, and outcomes.
主题：因果推断、RWE 与卫生经济学
相关性分数：5
期刊：Future science OA
公开日期：2026-08-03（电子公开）
期刊卷期日期：2026-Dec
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
BACKGROUND: Off-label underdosing of direct oral anticoagulants (DOACs) is common among Asian patients with atrial fibrillation (AF), partly reflecting concerns about bleeding, yet Southeast Asian data remain limited. This study aimed to characterize DOAC dosing patterns, identify predictors of off-label underdosing, and evaluate associated effectiveness and safety outcomes.
METHODS: We conducted a retrospective cohort using electronic health records (EHRs) from two tertiary hospitals in Thailand (2015-2023). Incident AF patients initiating dabigatran, rivaroxaban, apixaban, or edoxaban were included. Doses were classified as on-label, underdosed, or overdosed based on guideline criteria. Propensity score-based inverse probability of treatment weighting (PS-IPTW) Cox proportional hazards regression models was used to evaluate ischemic stroke or systemic embolism (ISSE) and bleeding outcomes.
RESULTS: Among 553 patients, 20.4% were underdosed, 6.3% overdosed, and 73.2% received on-label dosing. Rivaroxaban was most frequently underdosed. Older age and diabetes mellitus independently predicted underdosing. Compared to on-label dosing, underdosing was not associated with ISSE (adjusted hazard ratio [aHR] 0.48, 95% CI 0.11-2.16; p = 0.336) or bleeding (aHR 1.06, 95% CI 0.30-3.73; p = 0.924).
CONCLUSIONS: Off-label underdosing occurred in one-fifth of patients but was not associated with significant differences in ISSE or bleeding. Larger, prospective studies in broader Asian and non-Asian populations are warranted.
This study was conducted because doctors sometimes prescribe lower-than-recommended doses of direct oral anticoagulants (DOACs) for people living with atrial fibrillation (AF), especially in Asian populations, due to concerns about bleeding. However, it is unclear how often this happens in real-world practice in Thailand, what factors influence these decisions, and whether using lower doses affects patient outcomes such as stroke or bleeding.The researchers used electronic health records (EHRs) from two hospitals in Thailand to follow 553 people newly diagnosed with AF who started DOAC treatment between 2015 and 2023. They found that most people (about 73%) received recommended doses, but around 20% received lower-than-recommended doses, most commonly rivaroxaban. Older age and having diabetes were linked to a higher likelihood of receiving a lower dose. Importantly, when comparing people who received lower doses with those who received recommended doses, there were no meaningful differences in the risks of stroke or bleeding.These results suggest that although prescribing lower doses is relatively common, it may not provide clear benefits or harms in terms of major clinical outcomes. This highlights the need for careful, individualized decision-making rather than routine dose reduction based on concern alone. This study adds important real-world evidence from Southeast Asia, where data are still limited. It helps clinicians, researchers, and policymakers better understand prescribing patterns and supports the need for larger studies to guide safe and effective DOAC use across diverse populations.
9. Sample Size Reduction by Applying ML Based Causal Inference Methods.
主题：临床试验方法与统计实践
相关性分数：5
期刊：Pharmaceutical statistics
公开日期：2026
内容状态：待评估
为什么值得看：包含可供初筛的摘要；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
We conducted a comprehensive comparative analysis of causal machine learning (ML) methods to assess their utility in improving the efficiency of clinical trial designs with or without historical data. Specifically, we compared standard ANCOVA analysis used in a Randomized Controlled Trial (RCT) with several causal ML methods, including PROCOVA, TMLE, DML, and GRF. PROCOVA is gaining popularity in RCT design and requires a historical data for prognostic scores, but other methods can be applied with or without such data. Our primary focus was on strict RCT setting without borrowing historical control data, though we also explored the impact of borrowing data. The historical data used consisted of placebo data from two Phase 3 Ophthalmology studies with a continuous primary endpoint. We employed a generative AI approach, specifically Generative Adversarial Networks (GANs), to simulate RCT data from the historical data under various scenarios, varying treatment effects with and without treatment effect heterogeneity, RCT sizes, and bias. Results showed that causal ML methods can increase power even without borrowing historical data. For example, TMLE increased effective sample size by 21% in one scenario. In scenarios with borrowing of controls, PROCOVA increased power while controlling type 1 error, showing robustness to model misspecification.
10. Cost-effectiveness of finotonlimab plus bevacizumab versus sorafenib as first-line therapy in unresectable hepatocellular carcinoma in China.
主题：因果推断、RWE 与卫生经济学
相关性分数：5
期刊：Human vaccines & immunotherapeutics
公开日期：2026-07-27（电子公开）
期刊卷期日期：2026-Dec-31
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
Hepatocellular carcinoma (HCC) imposes a substantial health burden in China. Finotonlimab plus bevacizumab recently prolonged progression-free survival (PFS) and overall survival (OS) vs. sorafenib, but its economic value remains unknown. Here we evaluated the cost-effectiveness of finotonlimab plus bevacizumab vs. sorafenib from the Chinese healthcare system perspective. Parametric survival models were fitted to extrapolate PFS and OS. Total costs, life-years (LYs), quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), incremental net monetary benefit (INMB), and incremental net health benefit (INHB) were estimated at a willingness-to-pay (WTP) threshold of $27,906 per QALY. Uncertainty was evaluated by one-way and two-way sensitivity analyses, probabilistic sensitivity analysis (PSA), subgroup analyses, scenario analyses, and price simulations. In the base-case analysis, sorafenib yielded 1.74 LYs and 1.25 QALYs at a total cost of $10,303.10, whereas finotonlimab plus bevacizumab yielded 3.01 LYs and 2.18 QALYs at a total cost of $58,595.49. Compared with sorafenib, the combination increased costs by $48,292.39 and generated gains of 1.27 LYs and 0.93 QALYs, resulting in ICERs of $38,203.46 per LY and $51,899.31 per QALY. INMB (-$22,325.82) and INHB (-0.80 QALYs) were negative. Sensitivity analyses identified PFS utility and bevacizumab cost as key drivers, but all ICERs remained above the WTP threshold. In PSA, the mean ICER was $50561.81 per QALY, and the probability of cost-effectiveness was 0% at the prespecified threshold. Based on the assumptions and inputs used in the present model, finotonlimab plus bevacizumab was unlikely to be cost-effective compared with sorafenib at the prespecified WTP in China.
11. Cost-effectiveness analysis of disitamab vedotin plus toripalimab versus chemotherapy as first-line treatment for HER2-expressing advanced urothelial cancer.
主题：因果推断、RWE 与卫生经济学
相关性分数：4
期刊：Human vaccines & immunotherapeutics
公开日期：2026-08-18（电子公开）
期刊卷期日期：2026-Dec
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
The RC48-C016 trial conducted in China demonstrated that disitamab vedotin plus toripalimab (DV+Torip) significantly extended overall survival and progression-free survival in comparison to chemotherapy for patients with HER2-expressing advanced urothelial cancer. However, the economic value of this combination regimen remains uncertain. This study aimed to assess the cost-effectiveness of DV+Torip vs. chemotherapy as a first-line treatment for HER2-expressing advanced urothelial cancer from the Chinese healthcare system perspective. A partitioned survival model with a 10 y time horizon was developed to evaluate the cost-effectiveness. The primary outcomes included costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Sensitivity, subgroup, and scenario analyses were employed to examine the uncertainty associated with the model results. The ICER of DV+Torip vs. chemotherapy was estimated at $18,448.74 per QALY, which was below the willingness-to-pay (WTP) threshold of $40,334 per QALY. In the majority of sensitivity, subgroup, and scenario analyses, the ICER values remained below the WTP threshold, thereby affirming the robustness of these findings. However, in one scenario analysis, where treatment durations were not aligned with the median treatment cycles and subsequent drug treatment costs were excluded, the economic advantage of the DV+Torip group was nullified, resulting in an ICER of $66,303.62 per QALY. These results suggest that DV+Torip is cost-effective, though its economic advantage may be influenced by treatment duration and subsequent therapy costs.
12. Efficacy and safety of semaglutide injection in Indian patients with type 2 diabetes mellitus inadequately controlled on metformin: A phase 3, randomized, active-controlled, multicenter, non-inferiority trial (WIN-IND study).
主题：临床试验方法与统计实践
相关性分数：4
期刊：Metabolism open
公开日期：2026-08-05（电子公开）
期刊卷期日期：2026-Sep
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder with a rapidly rising global burden. Present study established the non-inferiority and evaluated the safety of Intas semaglutide (test) compared to Innovator semaglutide (reference) in patients with T2DM inadequately controlled on metformin.
METHODS: This prospective, randomized, open-label, multicenter phase 3 trial, conducted between July-2025 and February-2026, enrolled adult patients (18-65 years) with T2DM and HbA1c level ≥7%-<10.5% at baseline, who had been on diet, exercise and metformin (≥1500 mg/day). Randomized (1:1) patients received either test or reference product, once weekly from 1 to 24 weeks. Primary endpoint was the change in HbA1c level. Secondary endpoints were the change in fasting blood glucose (FBG) level, post-prandial blood glucose (PPBG) level, bodyweight, body mass index (BMI), and lipid parameters. Safety assessment included monitoring of treatment emerged adverse events (TEAEs).
RESULTS: Study analyzed 223 (safety set) and 217 (ITT set) patients. Baseline characteristics were comparable between treatment groups. In the ITT (LOCF) set, at week-24, LSM change in HbA1c was -1.50 vs. -1.65 in test vs. reference group, respectively; LSM difference was 0.16 (95% CI: -0.16 to 0.47, P = 0.3266), confirming non-inferiority of the test product. Other efficacy parameters (FBG and PPBG levels, bodyweight and BMI) were also similarly reduced in the test group. The incidence, severity, and pattern of TEAEs were similar, without new safety signals identified.
CONCLUSION: Intas semaglutide showed non-inferiority to reference semaglutide with comparable efficacy, immunogenicity, and safety which may provide a cost-effective alternative treatment option to Indian patients with T2DM.
CLINICAL TRIAL REGISTRATION NUMBER: CTRI/2025/06/089290.
13. Comparison of the efficacy and safety of acetaminophen versus NSAIDs for the treatment of chronic pain in older adults with osteoarthritis of the hip and knee: Findings from the randomized, double-blind, parallel-group, non-inferiority RETHINK study.
主题：临床试验方法与统计实践
相关性分数：4
期刊：Osteoarthritis and cartilage open
公开日期：2026-07-06（电子公开）
期刊卷期日期：2026-Sep
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
OBJECTIVE: This study aimed to evaluate the non-inferiority of acetaminophen compared with non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of chronic osteoarthritis-related pain in older adults.
DESIGN: This multicenter, randomized, double-blind, parallel-group study enrolled patients aged 65 years or older with osteoarthritis-related pain. Participants were randomly assigned to receive acetaminophen (1800 mg/day) or NSAIDs (loxoprofen 180 mg/day or celecoxib 200 mg/day). The primary endpoint was the change in Brief Pain Inventory (BPI) item 3 (worst pain) score from baseline to week 8. The secondary endpoints included the change in BPI item 3 score from baseline to week 4, quality of life, gastrointestinal disorders, and renal and liver function parameters.
RESULTS: Of the 400 patients enrolled, 191 and 197 were in the acetaminophen (mean age 73.6 years; 83.2% female) and NSAID groups (mean age 73.3 years; 74.6% female), respectively. The least-squares mean change in BPI item 3 scores at 8 weeks was -1.79 in the acetaminophen group and -1.94 in the NSAIDs group. The between-group difference in BPI item 3 scores change was 0.14 (95% CI, -0.33 to 0.61). No major safety concerns were identified; however, gastrointestinal disorders occurred more frequently with NSAIDs and were the most common cause of treatment discontinuation.
CONCLUSIONS: In this RETHINK study, acetaminophen achieved a similar reduction in osteoarthritis-related pain to NSAIDs in older adults after eight weeks; however, non-inferiority was not demonstrated. In terms of adverse events, acetaminophen was associated with fewer gastrointestinal disorders. These findings suggest that treatment choice may depend on the balance between analgesic efficacy and safety considerations.
TRIAL REGISTRATION NUMBER: The study is registered in the Japan Registry of Clinical Trials (jRCTs071200112).
14. Benefit of Linked-Color Imaging in Artificial Intelligence-Assisted Diagnosis of Early Gastric Cancer: A Pilot Study With Propensity Score Adjustment.
主题：因果推断、RWE 与卫生经济学
相关性分数：4
期刊：DEN open
公开日期：2026-07-28（电子公开）
期刊卷期日期：2027-Apr
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
BACKGROUND AND AIMS: Artificial intelligence (AI)-assisted endoscopy represents a promising approach for lesion detection, yet frequent false-positive detections impair clinical utility by disrupting examinations and diminishing physician confidence. Linked-color imaging (LCI), an image-enhanced endoscopy technique that amplifies mucosal and vascular contrast, may address this limitation. This investigation evaluated whether LCI reduces false-positive AI detections compared with white-light imaging (WLI).
METHODS: This retrospective study analyzed consecutive AI-assisted upper endoscopies performed between March 2024 and June 2025. WLI and LCI were performed sequentially within the same endoscopic session in each patient. False-positive AI detections were compared between modalities using two computer-aided detection (CAD) versions. Propensity score adjustment was used as a sensitivity analysis for baseline differences between CAD Versions I and II.
RESULTS: Of 66 initially screened cases, 63 remained after excluding patients with prior gastric surgery. LCI reduced false-positive AI detections compared with WLI (median 2 vs. 5; p < 0.001). In CAD version-stratified sensitivity analyses, LCI reduced false-positive AI detections in both Version I (5 to 2; p = 0.01) and Version II (2 to 0; p = 0.03). This reduction remained consistent across atrophic grades. Both imaging modalities identified all gastric lesions, achieving 100% detection sensitivity.
CONCLUSIONS: LCI assessment performed after WLI observation yielded fewer false-positive CAD-EYE detections while maintaining lesion detection sensitivity. However, because the observation sequence was fixed, these findings should be interpreted cautiously and require confirmation in prospective or counterbalanced studies.
UNLABELLED: Trial Registration: N/A (retrospective study).
15. Transcutaneous auricular vagus nerve stimulation combined with ciprofol for sedation in patients undergoing same-session bidirectional endoscopy: a randomized, double-blind, placebo-controlled, three-arm non-inferiority trial protocol.
主题：临床试验方法与统计实践
相关性分数：4
期刊：Annals of medicine
公开日期：2026-07-01（电子公开）
期刊卷期日期：2026-Dec
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
BACKGROUND: Transcutaneous auricular vagus nerve stimulation (taVNS) provides targeted modulation of the autonomic nervous system and descending pain pathways, exerting analgesic potential. However, high-quality evidence remains insufficient to determine whether taVNS can effectively replace opioids in sedation regimens for same-session bidirectional endoscopy while maintaining the quality of early postoperative recovery.
DISCUSSION: This study is a single-center, prospective, randomized, double-blind, placebo-controlled, three-arm non-inferiority trial. A total of 181 patients scheduled for painless same-session bidirectional endoscopy will be enrolled and randomly assigned using dynamic block randomization to one of three groups: Group S (sufentanil 0.1 µg/kg plus sham taVNS), Group T (normal saline plus active taVNS), and Group P (normal saline plus sham taVNS). All participants will receive ciprofol for sedation induction and maintenance. The primary outcome will be the quality of recovery at 24 h postoperatively, assessed using the 15-item Quality of Recovery scale (QoR-15), with a predefined non-inferiority margin (δ) of 6 points, which corresponds to the minimal clinically important difference of the QoR-15 scale. Secondary outcomes will include perioperative adverse events (pre-, intra-, and postoperative, including taVNS-related events), QoR-15 score at 1 h postoperatively, procedural and recovery efficiency indices, sedative dosage, and patient and endoscopist satisfaction scores. Blinding effectiveness will be assessed in all participants, and statistical analyses will follow the modified intention-to-treat principle.
CONCLUSION: This study protocol will rigorously assess the effectiveness and safety of taVNS as an alternative to opioid analgesics for sedation during same-session bidirectional endoscopy using, to our knowledge, the first three-arm design.Trial registration: Chinese Clinical Trial Registry (ChiCTR2600117962).
This study will provide the first systematic evaluation of the feasibility and efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) as an opioid-sparing alternative to sufentanil for ciprofol-based sedation during same-session bidirectional endoscopy.A three-arm randomized design incorporating a prespecified trial-sensitivity analysis will be used to rigorously validate the effectiveness of the standard regimen, enhancing the interpretability and credibility of the non-inferiority conclusion.An “active placebo” taVNS stimulation model combined with an improved standardized questionnaire for blinding assessment will be employed to address the well-recognized limitations of inadequate blinding in taVNS research.
16. Resuscitation in paediatric septic shock using vitamin C and hydrocortisone (RESPOND): The RESPOND randomised controlled trial statistical analysis plan.
主题：临床试验方法与统计实践
相关性分数：4
期刊：Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine
公开日期：2026-06-16（电子公开）
期刊卷期日期：2026-Sep
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
BACKGROUND: The Resuscitation in Paediatric Septic Shock using Vitamin C and Hydrocortisone (RESPOND) trial is a multicentre randomised controlled trial exploring whether the use of hydrocortisone alone, or in combination with vitamin C, increases time alive and free of vasopressors for critically ill children.
OBJECTIVE: To present the prespecified statistical analysis plan (SAP) for the RESPOND trial prior to finalising recruitment and locking the trial dataset.
DESIGN SETTING AND PARTICIPANTS: The RESPOND trial is a three-arm, parallel group, open-label, randomised controlled trial, recruiting in paediatric intensive care units in Australia, New Zealand, India, and Brazil. The planned sample size is 384 participants.
MAIN OUTCOME MEASURES: The primary outcome is time alive and free of inotropes/vasopressors, censored at 7 days post-randomisation. Secondary outcomes include clinical (e.g. alive and free of multi-organ dysfunction, length of stay), safety, health economics (e.g. incremental costs, quality-adjusted life years), and long-term outcomes (measured at 6 months post-randomisation; e.g. health-related quality of life).
RESULTS AND CONCLUSIONS: The SAP was designed by the Chief Investigators and approved by the RESPOND Steering Committee. Statistical analyses are summarised. The primary outcome will be analysed using quantile regression adjusted for stratification variables. Appropriate statistical comparisons between groups were planned and described in a way that is transparent, available to the public, verifiable, and predetermined before completion of data collection. The trial statistician, RESPOND Steering Committee members, and SAP authors remain blind to treatment allocation throughout the study. Data Safety and Monitoring Board members were provided with safety data with masked group identifiers during interim analyses. The RESPOND trial commenced recruitment in December, 2021, and aims to complete recruitment by mid-2026.
TRIAL REGISTRATION: ACTRN12621000247875.
17. Reproducibility, transparency, and open science: a cultural evolution is needed to move from ideals we celebrate to implementation.
主题：可复现研究与开放科学
相关性分数：3
期刊：BMC medical research methodology
公开日期：2026-08-22（电子公开）
期刊卷期日期：2026-Aug-22
内容状态：待评估
为什么值得看：暂缺摘要，需回到 PubMed 核验；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
18. Utility of serum HMGB1 in chronic obstructive pulmonary disease with pulmonary hypertension: A single-centre analysis.
主题：因果推断、RWE 与卫生经济学
相关性分数：3
期刊：Pulmonology
公开日期：2026-08-21（电子公开）
期刊卷期日期：2026-Dec
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) with pulmonary hypertension (PH) worsen outcomes, yet reliable prognostic biomarkers remain lacking.
RESEARCH QUESTION: We aimed to determine the prognostic value of serum high-mobility group Box 1 (HMGB1) in individuals experiencing AECOPD with concurrent PH and to examine its relationship with inflammatory and vascular markers.
STUDY DESIGN AND METHODS: Total 127 patients were divided into AECOPD-non-PH group (n = 71) and AECOPD-PH group (n = 56). Serum levels of HMGB1, interleukin-6 (IL-6), endothelin-1, tumour necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) were measured. Predictive performance was evaluated using receiver operating characteristic and multiple logistic regression analyses.
RESULTS: The AECOPD-PH group had significantly higher serum HMGB1, endothelin-1 and PaCO2 than the AECOPD-non-PH group. The combination of HMGB1, endothelin-1 and PaCO2 demonstrated superior diagnostic accuracy for PH, with an area under the curve of 0.751. HMGB1 levels correlated positively with IL-6 (ρ=0.295, p = 0.001) and TNF-α (ρ=0.302, p = 0.001), but negatively with VEGF (ρ=-0.232, p = 0.009). In risk stratification, HMGB1 ≥ 38.24 ng/mL predicted intermediate-high risk PH with 69.2% sensitivity, 64.7% specificity and an area under the curve of 0.700.
CONCLUSION: Serum HMGB1 was moderately associated with PH in patients with AECOPD, demonstrating its utility in risk assessment. However, these findings are specific to the acute exacerbation setting and should not be extrapolated to stable-phase COPD-associated PH; further studies in stable COPD populations are warranted.
19. Toxic optimism in clinical trial design.
主题：临床试验方法与统计实践
相关性分数：3
期刊：European journal of orthopaedic surgery & traumatology : orthopedie traumatologie
公开日期：2026-08-20（电子公开）
期刊卷期日期：2026-Aug-20
内容状态：待评估
为什么值得看：暂缺摘要，需回到 PubMed 核验；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
20. HIV prevention service disruption among transgender adults in the context of 2025 federal executive orders in the United States: a cross-sectional multi-state study.
主题：生存与复杂事件结局方法
相关性分数：3
期刊：Lancet regional health. Americas
公开日期：2026-08-11（电子公开）
期刊卷期日期：2026-Nov
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
BACKGROUND: In early 2025, the United States (U.S.) federal government issued several executive orders restricting healthcare access and non-discrimination protections for transgender and nonbinary (trans) populations. The current study investigated correlates of HIV prevention service disruptions among trans adults across five U.S. states.
METHODS: We analysed cross-sectional survey data of trans adults (Feb-April 2025) from the Priority Assessment in Trans Health Across States (PATHS2). This multi-state survey was conducted in five varying policy environments (Connecticut, Georgia, New York, Utah, and Washington). Analyses were restricted to participants currently using HIV prevention services, including PrEP (oral or long-acting) or HIV testing in the prior 12 months (N = 693). Main outcomes were (a) any HIV prevention service disruption (delayed or denied HIV prevention medications (PrEP: oral or long-acting), lost insurance or financial assistance coverage, reduced service availability, increased healthcare stigma) and (b) disruption breadth, modelled as ordinal (none/some [1-2 types]/significant [≥3 types]). Multivariable and ordinal logistic regressions assessed correlates across sociodemographic, psychosocial, and policy-related factors.
FINDINGS: Nearly two-thirds (64·5%, n = 447/693) of participants reported having experienced HIV prevention disruption; among this group. Among those reporting any disruption (n = 447), the most common disruption types included delayed/denied medications (53·2%, n = 238), reduced HIV service availability (50·3%, n = 225), lost coverage (40·9%, n = 183), and increased healthcare stigma (29·3%, n = 131). Compared with trans men, trans women had significantly higher odds of any disruption (aOR = 2·69, 95% CI 1·50-4·81) and greater disruption breadth (aOR = 1·85, 95% CI 1·16-2·93). Nonbinary individuals had elevated odds across all disruption types (aORs range = 2·99-6·58). Past-year discrimination was the strongest correlate of any disruption (aOR = 16·5, 95% CI 9·08-30·07) and breadth (aOR = 9·68, 95% CI 6·26-14·99). Black/African American participants had higher odds of any disruption compared with White participants (aOR = 2·17, 95% CI 1·06-4·46). State policy environment was not significantly associated with disruption in adjusted models.
INTERPRETATION: Past-year discrimination was the dominant correlate of disruption. State-level protective policies did not independently buffer against disruption in this short post-issuance window, suggesting that a federal policy shock of this magnitude may have exceeded the buffering capacity of state-level protections. Targeted, actionable responses, such as sustained funding for Black-trans-led community health organisations as trusted PrEP access points, anti-discrimination enforcement in healthcare, navigation services to maintain continuity of PrEP and prescription assistance during coverage instability, and insurance marketplace protections (e.g., Affordable Care Act) and programs (e.g., Medicaid, Ryan White) that explicitly prohibit gender-identity-based denials of HIV prevention coverage, are urgently needed.
FUNDING: The Royalty Research Fund at the University of Washington.