方法与临床研究雷达（2026-08-29）
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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. 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.
8. 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.
9. A multi-center, open-labelled, randomized controlled extended phase III non-inferiority clinical trial to evaluate the immunogenicity and tolerability of poliomyelitis vaccine (Vero cells), inactivated, Sabin strains administered with or without routine infant vaccines.
主题：临床试验方法与统计实践
相关性分数：4
期刊：Vaccine
公开日期：2026-08-27（电子公开）
期刊卷期日期：2026-Aug-27
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: Oral poliovirus vaccine (OPV) has been reported to cause vaccine-derived poliovirus and vaccine-associated paralytic poliomyelitis, and the limited global supply of conventional IPV has led many countries to rely on fractional-dose IPV regimens alongside OPV. The current study aims to assess the sIPV safety and immunogenicity when given concurrently with or in a staggered manner with routine immunization.
METHODS: A multi-country, multi-center, open-label, randomized controlled, extended phase III non-inferiority clinical trial was conducted with 1442 healthy infants aged 6-8 weeks from Bangladesh and Pakistan enrolled and randomized into four groups, i.e., co-administration group 1 (group C1), co-administration group 2 (group C2), staggered administration group 1 (group S1) and staggered administration group 2 (group S2). Antibody levels were determined using the collected sera for immunogenicity evaluation. The difference in seroconversion rates between the coadministration group and the staggered administration group is compared using the Cochran-Mantel-Haenszel χ2 (CMH-χ2) test, stratified by study site. Non-inferiority is concluded if the lower bound of the 95% confidence interval (CI) for the rate difference (coadministration group minus staggered administration group) is greater than -10%. The trial was registered prior to patient enrollment at clinicaltrials.gov (NCT05850364), and the protocol and statistical analysis plan are available at https://clinicaltrials.gov/study/NCT05850364. The trial is closed to new participants.
FINDINGS: The post-vaccination seroconversion rates for PV I were 90.3% (306/339) in group C1 and 87.0% (261/300) in group S1, for PV II, 91.7% (311/339) in group C1 and 91.3% (274/300) in group S1 and for PV III, 86.4% (293/339) in group C1 and 92.3% (277/300) in group S1. Among adverse reactions (ARs) reported within 7 days of vaccination, the incidence was similarly high in both the co-administration and staggered vaccination groups (92.8% vs. 95.5%).
INTERPRETATION: Our results demonstrated favorable safety and immunogenicity of co-administration of sIPV with other routine infant vaccines according to a 3-dose primary immunization schedule.
10. Brain-computer interface clinical trial design considerations and clinical outcome assessments in pivotal studies: a summary of the 11th BCI society meeting 2025 workshop.
主题：临床试验方法与统计实践
相关性分数：4
期刊：Journal of neural engineering
公开日期：2026-08-26（电子公开）
期刊卷期日期：2026-Aug-26
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 Brain Computer Interface (BCI) Society Meeting 2025 held a workshop in collaboration with the Implantable BCI Collaborative Community (iBCI-CC) to discuss the selection, development and validation of clinical trial outcome assessments (COAs) for pivotal studies of BCIs. The iBCI-CC Clinical Study Endpoints Workgroup aims to build consensus on a COA framework that can meet the demands of emerging iBCI trials. Approach: The workshop brought together diverse stakeholders from the iBCI-CC community and beyond, including industry, academic and government institutions to engage in pre-competitive collaborative discussion. Main results: Through presentations, panel discussions and breakout groups, workshop participants highlighted meaningful aspects of health (MAHs) relevant to iBCI users, clarified the need to define corresponding concepts of interest (COIs) and to identify or adapt clinical outcome assessments (COAs) capable of capturing both functional impact and real-world use. Key challenges highlighted during the workshop are patient heterogeneity, the lack of widely validated and fit-for-purpose COAs, and the need to capture meaningful outcomes in home and daily-life environments. Lessons drawn from trials such as ADAPT-PD underscore the value of capturing device performance in home and daily-life settings, highlighting the need for context-sensitive and flexible metrics that reflect patient priorities. Significance: This workshop lays a foundation for the iBCI-CC Clinical Study Endpoints Workgroup to establish a transparent process for identifying MAHs and COIs that are suitable for specific iBCI technologies, patient-informed, and conducive to regulatory approval and reimbursement. By combining rigorous, quantitative assessment with patient-informed goals, iBCI clinical trials can advance toward safe, effective, and accessible neurotechnologies that enhance how a person with a severe motor impairment feels, functions and survives.
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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. Endoscopic Surveillance in Serrated Polyposis Syndrome, Two or Three-Year Intervals: A Non-inferiority Randomized Trial.
主题：临床试验方法与统计实践
相关性分数：4
期刊：Digestive diseases and sciences
公开日期：2026-04-21（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: Serrated polyposis syndrome, the most prevalent colonic polyposis, confers an increased colorectal cancer risk. Guidelines recommend close colonoscopy surveillance, but recent data suggest low neoplasia rates, supporting longer colonoscopy intervals.
AIMS: Compare advanced neoplasia incidence between two- and three-year surveillance.
METHODS: A multicentre, randomized non-inferiority trial was conducted (May 2021-November 2024) in six Spanish hospitals. Patients fulfilling the 2019 WHO criteria for serrated polyposis syndrome, including newly diagnosed individuals and those already under surveillance, with no advanced neoplasia and fewer than five relevant polyps at their previous colonoscopy, were randomized to surveillance at 2 or 3 years. The primary endpoint was advanced neoplasia incidence.
RESULTS: A total of 131 patients with serrated polyposis syndrome were included (47.3% women; mean age 66.1). Seventy-two were assigned to 2-year and 59 to 3-year colonoscopy. Among 771 resected lesions, 2.4% were advanced adenomas or advanced serrated polyps; no colorectal cancer was detected. The proportion of patients with advanced neoplasia in the surveillance colonoscopy was 6.9% (2-year) vs 13.6% (3-year), with no statistical difference (p = 0.208) but with a risk difference of + 6.7% (95% CI -4.1 to 17.5%) exceeding the pre-specified non-inferiority margin of + 10%. Time since serrated polyposis syndrome diagnosis ≤ 3 years was associated with advanced neoplasia (OR 4.4; 95% CI 1.56-14.71; p = 0.024).
CONCLUSIONS: In patients with serrated polyposis syndrome, extending colonoscopy surveillance to a three-year compared with a two-year interval yielded inconclusive evidence regarding non-inferiority for advanced neoplasia incidence. The early years following serrated polyposis syndrome diagnosis were identified as a risk factor for advanced neoplasia.
TRIAL REGISTRATION: Clinical Trial Registry ClinicalTrials.gov (NCT04906343). Date: 5-10-2021.
18. Equipoise lost: Prioritizing patient safety and early access to promising cancer therapies in clinical trial design by reimagining crossover.
主题：临床试验方法与统计实践
相关性分数：3
期刊：The oncologist
公开日期：2026-08-28（电子公开）
期刊卷期日期：2026-Aug-28
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。
19. Clinical and public health economic impact of rapid strain-matched vaccination in influenza pandemic mitigation: A UK-like population dynamic transmission model.
主题：因果推断、RWE 与卫生经济学
相关性分数：3
期刊：Human vaccines & immunotherapeutics
公开日期：2026-08-28（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。
Influenza A virus H5N1 has recently circulated at unprecedented levels in birds and mammals, causing sporadic human infections. Using a susceptible-exposed-infectious-recovered (SEIR) dynamic transmission model of a UK-like population, this study aimed to quantify reductions in morbidity, mortality, and healthcare utilization attributable to rapid deployment of a strain-matched pandemic influenza vaccine; to compare outcomes across egg-based and cell-based vaccine platforms; to evaluate the economic impact of nonpharmaceutical interventions (NPIs) and their interaction with vaccination timing; and to estimate the impact of earlier or delayed vaccine availability across a full spectrum of pandemic transmissibility and severity scenarios. In the absence of NPIs, a 16-week vaccination campaign starting 16 weeks post-pandemic declaration reduced infections by 3.0 million and deaths by 28,000, with greater benefits observed in low-transmissibility scenarios. A cell-based vaccine with equivalent timing further reduced deaths by 5.0%, with additional gains in scenarios involving faster vaccine production. NPIs (average cost, £208 billion) enhanced vaccine effectiveness across all pandemic types, most markedly in high-transmissibility events; cell-based vaccine additionally reduced NPI costs by 0.9% relative to egg-based vaccine. Conversely, delays in vaccine availability increased both mortality and economic costs. These findings highlight the need for robust and agile vaccine development, registration, and distribution infrastructures, as well as flexible response strategies adaptable to varying pandemic severity and transmissibility. Policymakers should consider adopting a comprehensive framework integrating health outcome metrics and the economic impact of NPIs to inform vaccine procurement and deployment decisions.
20. Utility of intracellular enhancement for improving hepatic lesion visibility at gadoxetic acid-enhanced hepatobiliary-phase MRI.
主题：因果推断、RWE 与卫生经济学
相关性分数：3
期刊：European journal of radiology open
公开日期：2026-08-19（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: To investigate the utility of the intracellular enhancement (ICE) technique that suppresses extracellular signal component for shortening the gadoxetic acid (EOB)-enhanced hepatobiliary-phase (HBP) delay time while maintaining lesion visibility.
METHODS: In this prospective study, patients who underwent EOB-enhanced MRI were screened and those with HBP hypointense hepatic lesions were included. HBP images were acquired at 10 and 20 min post-EOB injection, with and without ICE (i+- and i–10 and 20 min HBP). One representative lesion per patient was evaluated. The lesion-to-liver contrast ratio (CR) was calculated. Two radiologists assessed overall image quality and lesion visibility on a five-point scale. The primary outcome was lesion visibility, which was assessed qualitatively using subjective lesion visibility scores and quantitatively using CR. Differences between paired groups were determined by using a two-sided Wilcoxon signed-rank test.
RESULTS: Eighty-one patients were included. Overall image quality was significantly worse with ICE at both 10- and 20-min HBP (10 min: mean 3.8 vs 3.1; 20 min: 4.0 vs 3.3; both p < 0.01). There was no significant difference in the CR between i+-10 min and i–20 min HBP (median 1.58 vs 1.54; p = 0.48). Furthermore, lesion visibility scores on i+-10 min HBP were significantly higher than those on i–20 min HBP (mean 4.1 vs 3.9; p < 0.01).
CONCLUSION: ICE has the potential to reduce delay time without compromising lesion visualization; however, further studies with larger sample size.