方法与临床研究雷达（2026-10-04）
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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-Oct-15
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. A Bayesian Adaptive Design for Assessing Treatment Effect Consistency in Bridging Studies.
主题：临床试验方法与统计实践
相关性分数：5
期刊：Statistics in medicine
公开日期：2026-Oct
内容状态：待评估
为什么值得看：包含可供初筛的摘要；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。
Bridging studies serve as an efficient approach to evaluate the applicability of findings from an original study to a new population. We propose a Bayesian adaptive design for bridging studies with time-to-event endpoints, aiming to assess the consistency of treatment effects with those observed in the original study. The design adopts a group sequential framework, using posterior probabilities at interim and final analyses to evaluate the evidence for consistency between the bridging and original studies. If strong evidence of consistency or inconsistency is observed, the trial may be stopped early to conserve sample size. Additionally, a sample size recalculation strategy based on Bayesian predictive probability is incorporated to enhance flexibility. Simulation studies demonstrate that, compared to a commonly used method, the proposed design offers favorable operating characteristics. It maintains control of the empirical type I error rate through prespecified calibration, accounting for interim analyses (IAs) and sample size adaptation, and yields substantial sample size savings when the treatment effect in the bridging study is either highly consistent or clearly inconsistent with that of the original study.
5. A Practical Guide to Optimal Adaptive Two-Stage Designs for Various Endpoint Types.
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。
Adaptive designs are frequently used to adjust sample sizes based on interim data, ensuring reliable conclusions while protecting resources. To maximize trial efficiency, design parameters can be optimized to minimize an objective function (e.g., the expected sample size) while rigorously controlling overall error rates or further operating characteristics. However, existing methodological guidance for optimal adaptive designs mainly focuses on normally distributed data or discrete optimizations for binary data, leaving a limited practical framework to practitioners who work with other common endpoint types. We address this by demonstrating how the asymptotic normal approximations of standard test statistics enable the optimization framework to be systematically applied across diverse endpoint types, including binary and time-to-event data. Furthermore, we highlight critical pitfalls in using optimal adaptive designs for two-sided testing. The results demonstrate that optimizing design parameters can substantially decrease expected sample sizes and improve conditional power compared to standard group-sequential designs. Using this guidance, we aim to enable researchers to efficiently plan clinical trials in a broad spectrum of clinical settings, a factor that is especially crucial in rare disease research where only limited patient populations are available.
6. Evaluating the Impact of Outcome Delay on the Efficiency of Sample Size Re-Estimation.
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。
Sample size re-estimation (SSR) can be a powerful tool to ensure that a clinical trial meets its pre-specified power requirements when uncertainty regarding a design parameter exists at the planning stage. However, long-term primary endpoints can be harmful to the efficiency of this trial design. If recruitment is continued while treatment outcomes are awaited, long delays can potentially lead to a large number of ‘pipeline’ participants being recruited in the trial that do not contribute to the interim analysis. This may lead to a larger number of recruited participants than are actually deemed required, resulting in an over-powered trial with high cost. This paper studies the exact impact of such outcome delay on the efficiency of ‘internal pilot’ type SSR designs. The distribution of the final sample size post SSR is obtained under various delay lengths for both continuous and binary outcome data; how delay impacts the precision of the final sample size estimate is then discussed. Precisely, the impact of delay on this precision is assessed through RMSE, as well as two more novel metrics, termed the delay impact and cost. The results indicate that with an increase in delay length, the delay impact increases, inflating average sample size and power. However, the severity of the effect of delayed outcomes depends highly on the exact trial setting. Trials where the re-estimated sample size is smaller than originally planned suffer the most from delayed outcomes, often leading to an over-powered trial. However, the impact of delay is substantially less if the originally planned sample size remains smaller than the re-estimated sample size.
7. 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.
8. DUBHE-H-308 study protocol: rationale and adaptive design of a randomized, open-label, seamless phaseII/III trial of iparomlimab and tuvonralimab (QL1706)-based regimens versus sintilimab plus bevacizumab as first-line treatment for advanced hepatocellular carcinoma.
主题：临床试验方法与统计实践
相关性分数：4
期刊：Future oncology (London, England)
公开日期：2026-10-01（电子公开）
期刊卷期日期：2026-Oct-01
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。
No randomized trial has compared multiple immunotherapy-based combination strategies head-to-head in first-line advanced HCC, where approved doublet regimens achieve objective responses in fewer than one-third of patients. Iparomlimab and Tuvonralimab (QL1706), a new-type bifunctional combinedantibody (anti-PD-1/anti-CTLA-4 dual checkpoint inhibitor), deepens antitumor immunity while preserving tolerability. DUBHE-H-308 evaluates whether QL1706-based regimens, including a triplet with bevacizumab and oxaliplatin-based chemotherapy, can improve first-line outcomes in advanced HCC. DUBHE-H-308 (NCT05976568) is a prospective, randomized, open-label, multicenter, inferentially seamless phase II/III trial comparing three QL1706-based regimens against sintilimab plus bevacizumab in previously untreated advanced HCC. Three adaptive elements are incorporated: arm selection after phase II; seamless integration of phase II data into the phase III overall survival analysis; and a group-sequential interim analysis. Phase II co-primary endpoints are objective response rate and safety; the phase III primary endpoint is overall survival. Phase II enrollment is complete; interim data have guided regimen selection and confirmed transition to the confirmatory phase III stage. If successful, DUBHE-H-308 would provide the first randomized evidence supporting a triplet first-line strategy combining dual-checkpoint blockade, anti-VEGF therapy, and chemotherapy in advanced HCC, potentially establishing a new treatment standard. The adaptive framework maximizes efficiency without compromising confirmatory rigor.Clinical trial registration: ClinicalTrials.gov identifier NCT05976568.
Advanced liver cancer that cannot be removed by surgery is usually treated with drug combinations, but current two-drug regimens shrink tumors in fewer than one in three patients. QL1706 is a new “two-in-one” antibody that releases two of the brakes cancer uses to hide from the immune system. The DUBHE-H-308 study tests whether QL1706-based combinations especially a “triplet” adding bevacizumab, which cuts off the tumor’s blood supply, and platinum-based chemotherapy, improve outcomes for previously untreated patients, compared with the standard combination of sintilimab plus bevacizumab. Patients at multiple hospitals were randomly assigned to treatment groups. The trial uses an adaptive design: an early stage compared the combinations and selected the most promising one, and the study then moved into a larger confirmatory stage that measures how long patients live.Enrollment in the early stage is complete, and interim results confirmed the move into the final confirmatory stage. If positive, this would be the first randomized evidence that a three-drug strategy dual immune activation, anti-blood-vessel therapy, and chemotherapy works as a first-line treatment for advanced liver cancer, and could become a new standard of care.
9. Cost-effectiveness of Orca-T vs allo-HCT with conventional GVHD prophylaxis for the treatment of advanced hematologic malignancies in the United States.
主题：因果推断、RWE 与卫生经济学
相关性分数：4
期刊：Journal of medical economics
公开日期：2026-09-29（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: Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative therapy for patients with hematologic malignancies, but its success is limited by graft‑versus‑host disease (GVHD), which carries considerable clinical and economic burden. A cost-effectiveness model was developed to evaluate whether the higher upfront costs of allogeneic regulatory T cell-based immunotherapy with HSPC and T cells-vldq (Tregzi [Orca-T; Orca Bio, Menlo Park, CA, USA]) are offset by reductions in GVHD and associated healthcare costs compared with conventional allo-HCT using TAC/MTX or PTCy.
METHODS: A three-state partitioned survival model (relapse-free, relapsed, and dead) with a lifetime horizon and monthly cycles was developed. Overall survival and relapse-free survival data from the Phase 3 Precision-T study (ClinicalTrials.gov Identifier NCT05316701) were incorporated using a cure-mixture modeling approach to estimate long-term survival, relapse status, and cure fraction for patients. Costs included transplant procedure, GVHD management, infection management, and terminal care. Outcomes included life-years, quality-adjusted life-years (QALYs), and direct healthcare costs. Both costs and outcomes were discounted at 3% annually. A scenario analysis was conducted to determine the cost-effectiveness of Orca-T vs allo-HCT with PTCy for GVHD prophylaxis, and sensitivity analyses were conducted to test the uncertainty of the model inputs.
RESULTS: Orca‑T was associated with lower lifetime costs ($1,026,856 vs $2,170,875) and higher QALYs (15.28 vs 13.00) than conventional allo‑HCT with TAC/MTX, yielding cost savings of $1,144,019 and a gain of 2.28 QALYs per patient. GVHD-related costs were substantially lower with Orca‑T ($495,447 vs $1,998,621). Compared with PTCy, Orca‑T remained dominant, with cost savings of $158,144, a gain of 2.85 QALYs, and lower GVHD-related costs ($476,448 vs $999,945).
CONCLUSIONS: Orca‑T reduced costs and increased QALYs versus conventional allo‑HCT with TAC/MTX or PTCy, driven by lower GVHD and infection burden. These findings support Orca‑T as a high‑value treatment option.
10. WIse CHoices in the ICU (WICH-ICU): Protocol and Statistical Analysis Plan for a Stepped-Wedge Cluster Randomized Trial of Choosing Wisely Interventions in Swedish Intensive Care Units.
主题：临床试验方法与统计实践
相关性分数：4
期刊：Acta anaesthesiologica Scandinavica
公开日期：2026-Nov
内容状态：待评估
为什么值得看：包含可供初筛的摘要；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: Healthcare overuse, including unnecessary diagnostic testing and procedures, contributes to patient harm, increased healthcare costs, and resource waste. The Choosing Wisely initiative aims to reduce low-value care through evidence-based recommendations. However, limited evidence exists regarding the safety and effectiveness of implementing Choosing Wisely recommendations in intensive care settings.
METHODS: The WICH-ICU is a registry-based stepped-wedge cluster randomized controlled trial designed to evaluate the implementation of specific Choosing Wisely interventions in Swedish intensive care units (ICUs). The study will include adult patients treated in participating Swedish ICUs. The intervention consists of three parts of the Choosing Wisely recommendations: (1) reduced frequency of arterial blood gas sampling, (2) reduced routine laboratory testing, and (3) reduced routine chest radiography. The primary outcome is 30-day mortality. Secondary outcomes include ICU length of stay, duration of mechanical ventilation (invasive and noninvasive), continuous renal replacement therapy duration, and ICU readmission within 72 h. Intervention data, testing intensity (arterial blood gas samples, laboratory tests, and chest radiographs per patient-day), will be collected through local monitoring, while outcome data will be obtained from the Swedish Intensive Care Registry (SIR). The stepped-wedge design allows each participating ICU to serve as its own control, with randomized timing of intervention implementation.
DISCUSSION: This study will provide evidence on the safety and effectiveness of implementing Choosing Wisely recommendations in intensive care settings. The stepped-wedge cluster randomized design minimizes contamination while allowing all participating sites to eventually receive the intervention. The results will inform evidence-based de-implementation strategies in critical care.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT07013175.
11. Cost-effectiveness of an online personalised parenting intervention to prevent affective disorders in high-risk adolescents compared to a standard educational package.
主题：因果推断、RWE 与卫生经济学
相关性分数：4
期刊：Journal of affective disorders
公开日期：2026-09-07（电子公开）
期刊卷期日期：2026-Dec-15
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: Adolescent depression is associated with substantial health and economic burden. Preventive interventions that strengthen parenting skills show promise in reducing depressive symptoms and improving adolescent well-being. However, evidence on the cost-effectiveness of scalable online parenting interventions remains limited.
OBJECTIVES: To evaluate the cost-effectiveness of an online personalised parenting (PP) programme - Partners in Parenting - designed to prevent affective disorders in high-risk adolescents, compared with a standard educational package.
METHODS: This trial-based economic evaluation was conducted alongside a randomised controlled trial of 512 parent-adolescent dyads (256 per arm). Analyses adopted UK public sector and societal perspectives over 15 months. Costs (2022-2023 GBP) were collected prospectively. Utilities from EQ-5D-Y and CHU9D were used to estimate quality-adjusted life-years (QALYs). The base case used bivariate regression of costs and QALYs with multiple imputations under intention-to-treat. Incremental cost-effectiveness ratios, net monetary benefits, and cost-effectiveness acceptability curves were estimated. Sensitivity analyses assessed robustness.
RESULTS: In the adjusted multiply imputed base-case analysis, mean incremental public-sector costs were £639 (95% CI £272 to £988) and mean incremental QALYs were 0.013 (95% CI -0.021 to 0.042), corresponding to a 13%-27% probability of cost-effectiveness at willingness-to-pay thresholds of £20,000-£30,000 per QALY. Complete-case analysis suggested lower costs and higher QALYs but with substantial uncertainty.
CONCLUSIONS: Over the 15-month trial horizon, the personalised parenting programme was associated with higher costs, a small and uncertain gain in QALYs, negative incremental net monetary benefit, and a low probability of being cost-effective at NICE-recommended willingness-to-pay thresholds.
12. 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-Oct-03
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.
13. Survodutide for Obesity in Chinese Adults: Phase 3 Randomized Trial Design and Baseline Characteristics (SYNCHRONIZE™-CN).
主题：临床试验方法与统计实践
相关性分数：4
期刊：Diabetes therapy : research, treatment and education of diabetes and related disorders
公开日期：2026-08-14（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。
INTRODUCTION: We aimed to describe the rationale, design, and overall baseline characteristics of the trial evaluating the efficacy, safety, and tolerability of survodutide in Chinese adults with overweight or obesity (SYNCHRONIZE™-CN, NCT06214741).
METHODS: In this 76-week, multicenter, randomized, double-blind, placebo-controlled, phase 3 trial, Chinese participants were randomized 1:1:1 to once-weekly subcutaneous survodutide (3.6 mg or 4.8 mg) or placebo plus lifestyle intervention. Participants with either body mass index (BMI) ≥ 28 kg/m2 or BMI ≥ 24 kg/m2 and at least one obesity-related complication were eligible. The primary endpoints were the percentage change in body weight and achievement of body weight reduction ≥ 5% from baseline to week 52.
RESULTS: At baseline, participants (N = 306) had a mean age of 36.9 years, body weight 93.9 kg, waist circumference 105.6 cm, BMI 33.2 kg/m2, triglycerides 2.2 mmol/L. 49% were women. 72.9% had at least one obesity-related complication, with metabolic dysfunction‑associated steatotic liver disease (48.4%), dyslipidemia (42.2%), hypertension (27.8%), and type 2 diabetes mellitus (16.7%) being the most prevalent, followed by obstructive sleep apnea (4.6%) and cardiovascular diseases (4.2%). In total, 19.6% had prediabetes.
CONCLUSIONS: This trial was designed to provide a robust evaluation of efficacy and safety of survodutide for the treatment of obesity or overweight in Chinese adults.
TRIAL REGISTRATION: Clinical Trials.gov identifier, NCT06214741.
14. Transitions in depressive symptom states among adults with subthreshold depression: Associations with lifetime trauma exposure and combined lifestyle in a multistate Markov study.
主题：生存与复杂事件结局方法
相关性分数：4
期刊：Journal of affective disorders
公开日期：2026-08-04（电子公开）
期刊卷期日期：2026-Dec-01
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: Subthreshold depression is common, but whether lifetime trauma exposure and combined lifestyle are differentially associated with symptom transitions remains unclear.
METHODS: We analyzed a prospective community cohort in Shenzhen, China, of adults aged 18-65 years with a Patient Health Questionnaire-9 (PHQ-9) score ≥ 5 and no depressive disorder at baseline. Depressive symptom states (Normal, Mild, and Moderate/Severe) were assessed repeatedly over 36 months. Continuous-time multi-state Markov models estimated transition intensities, probabilities, and hazard ratios (HRs) for lifetime trauma exposure and a five-component combined lifestyle score, adjusting for demographic, socioeconomic, and health-related covariates.
RESULTS: Among 2361 participants (mean age, 37.30 years; 61.9% women), recovery transitions were more frequent than worsening transitions. The monthly Mild-to-Normal intensity was 0.131 (95% CI, 0.100-0.171), 2.47 times the Mild-to-Moderate/Severe intensity; Moderate/Severe-to-Mild was highest (0.205; 95% CI, 0.158-0.272). Lifetime trauma exposure was associated with lower Mild-to-Normal (HR, 0.54; 95% CI, 0.42-0.69) and Moderate/Severe-to-Mild rates (HR, 0.52; 95% CI, 0.41-0.65). Unfavorable lifestyle was associated with a lower Mild-to-Normal rate (HR, 0.70; 95% CI, 0.53-0.92) and a higher Mild-to-Moderate/Severe rate (HR, 1.60; 95% CI, 1.13-2.25). Those with both exposures had the lowest Mild-to-Normal rate (HR, 0.39; 95% CI, 0.26-0.59) and a higher Mild-to-Moderate/Severe rate (HR, 1.69; 95% CI, 1.05-2.73).
CONCLUSIONS: Lifetime trauma exposure was associated with lower recovery rates, whereas an unfavorable lifestyle was associated with lower recovery and higher worsening rates. These associations may inform trauma-informed assessment and lifestyle support for adults with subthreshold depression.
15. 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).
16. 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.
17. Evidence supporting European Medicines Agency drug approvals (2020-2023): A cross-sectional study of trial design and outcomes.
主题：临床试验方法与统计实践
相关性分数：4
期刊：Clinical trials (London, England)
公开日期：2026-04-07（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: The strength and transparency of clinical trial evidence supporting drug approvals have become increasingly scrutinized, particularly considering the increased use of regulatory flexibility and expedited pathways. While US Food and Drug Administration standards have been extensively analyzed, evidence standards at the European Medicines Agency remain less well-characterized. Thus, this study aims to systematically assess the design, quality, and outcomes of pivotal efficacy trials supporting European Medicines Agency drug approvals for new active substances between 2020 and 2023.
METHODS: We conducted a cross-sectional analysis of drugs receiving positive opinions from the European Medicines Agency’s Committee for Medicinal Products for Human Use and subsequent approval by the European Commission between January 2020 and December 2023. Data were extracted from European Public Assessment Reports and European Medicines Agency medicine databases. Key variables included trial design features, primary endpoint type and achievement status, and justification for approval in cases of failed efficacy endpoints.
RESULTS: Between 2020 and 2023, 227 new drugs were approved by the European Medicines Agency for 234 indications. Of these, 69 (30.4%) were granted orphan designation, and 53 (23.3%) were approved via an expedited pathway, most commonly conditional approval (29 drugs, 12.8%). Cancer was the leading therapeutic area, accounting for 59 approvals (26.0%). Approvals were supported by 404 pivotal clinical trials. Of the 227 drugs, 177 (78.0%) were supported by at least one randomized controlled trial, of which 138 (78.0%) were blinded. Out of those, 139 (78.5%) were supported exclusively by superiority trials. Regarding endpoint classification, 124/227 drugs (54.6%) relied exclusively on surrogate endpoints and 69 (30.4%) on clinical endpoints. Overall, 22 approvals (9.7%) were supported by at least one pivotal trial in which at least one primary endpoint was not met; in five of these cases (22.7%), the failed trial was the sole pivotal trial. The most common rationale for approval despite null primary results was reliance on the totality of evidence, secondary endpoints, or clinical judgment (nine products; 40.9%).
CONCLUSION: Our findings reveal substantial variability in the design and evidentiary strength of pivotal trials supporting European Medicines Agency approvals between 2020 and 2023. While the majority of studies were randomized controlled trials, reliance on surrogate endpoints was common. That 10% of approvals were based on pivotal trials with null primary endpoints highlights the nuanced role of regulatory judgment in therapeutic evaluation. These findings prompt reflection on evolving evidence standards in drug regulation and underscore the need for transparency and consistent justifications.
18. Diagnostic utility of delayed cerebral angiography in suspected artery of Percheron infarction presenting as bilateral paramedian thalamic infarction: A case report.
主题：因果推断、RWE 与卫生经济学
相关性分数：3
期刊：Radiology case reports
公开日期：2026-09-19（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。
The artery of Percheron (AOP) is a rare anatomical variant in which a solitary perforating artery arising from a unilateral posterior cerebral artery supplies both paramedian thalami, with or without the rostral midbrain. Occlusion of the AOP results in a characteristic pattern of bilateral paramedian thalamic infarction; however, diagnosis is often challenging because the responsible vessel is rarely visualized on routine vascular imaging. A 68-year-old man was admitted to our hospital with severe disturbance of consciousness. On admission, his Glasgow Coma Scale score was E1V1M4 and his National Institutes of Health Stroke Scale score was 40. Magnetic resonance imaging demonstrated acute bilateral paramedian thalamic infarctions. Magnetic resonance angiography (MRA) did not clearly visualize the artery of Percheron; a small perforating branch arising from the left P1 segment appeared poorly visualized or interrupted, although this finding could reflect the spatial-resolution limitations of MRA. Given the characteristic bilateral paramedian thalamic infarct pattern, artery of Percheron infarction was suspected. The patient was treated conservatively with dual antiplatelet therapy and rehabilitation. After his systemic condition had stabilized and his level of consciousness had improved, digital subtraction angiography (DSA) was performed on hospital day 30 to reassess the posterior circulation and perforating arterial anatomy. DSA demonstrated a perforating artery arising from the left P1 segment and coursing toward the bilateral paramedian thalami, anatomically consistent with the artery of Percheron. Based on the characteristic infarct distribution together with the angiographic anatomy, artery of Percheron infarction was considered highly likely, although the angiographic finding did not directly prove that this vessel had been the acute culprit. After 45 days of hospitalization, the patient was transferred to a rehabilitation hospital; he was able to communicate verbally but remained wheelchair dependent, with a modified Rankin Scale score of 4. This case highlights the potential diagnostic value of delayed DSA in selected patients with suspected artery of Percheron infarction. Delayed angiography may provide useful anatomical information after the patient’s clinical condition has stabilized; however, the angiographic findings should be interpreted together with the characteristic infarct distribution rather than as direct proof of the acute culprit vessel.
19. High-Dimensional Multimodal Data Integration for Immune-Driven Diseases: A Practical Guide.
主题：统计建模与试验设计方法
相关性分数：3
期刊：Methods in molecular biology (Clifton, N.J.)
公开日期：2027
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。
Recent advances in multiomics technologies have revolutionized the study of immune-driven diseases by enabling high-dimensional, single-cell resolution analyses. This chapter provides a practical guide for integrating CyTOF (mass cytometry) and single-cell RNA sequencing (scRNA-seq) data to address key challenges in this field. The integration of these modalities allows for consistent and reproducible cell type annotation, the transfer of annotations to assist in characterizing difficult-to-identify populations, and the transcriptional characterization of rare and heterogeneous subpopulations. Using tools such as OMIQ and R, the chapter outlines workflows for preprocessing, normalization, and scaling of CyTOF data, as well as dimensionality reduction and clustering techniques. The integration process involves creating Seurat objects, identifying common features, and using anchor-based methods to link CyTOF and scRNA-seq datasets. The chapter also discusses the use of multimodal deep learning techniques for rare subpopulation detection and emphasizes the importance of reproducibility and standardization in multiomics integration. By leveraging these methodologies, researchers can gain deeper insights into cellular heterogeneity and function, ultimately enhancing the understanding of immune-driven diseases. The chapter concludes by addressing integration challenges and proposing future directions for improving model interpretability and capturing nonlinear molecular interactions.
20. High-Dimensional Immunophenotyping of Human Leukocytes by Spectral Cytometry.
主题：统计建模与试验设计方法
相关性分数：3
期刊：Methods in molecular biology (Clifton, N.J.)
公开日期：2027
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。
Spectral cytometry has rapidly evolved over the past two decades. The development of complete spectral analysis using the flow cytometer as a spectrometer has been actualized due to advances in optics, detectors, and electronics that have made single-cell flow spectroscopy a reality. Polychromatic flow cytometry is a complex process, including the design of antibody panels and instrument compensation. Spectral cytometry has contributed significantly to effectively dealing with the complexity of polychromatic flow cytometry. It has substantial potential to improve primary and clinical research. Here, we provide an overview of the methodology to develop a 15-color human polychromatic flow cytometry panel using spectral flow cytometry.