方法与临床研究雷达（2026-09-26）
检索窗口：最近 14 天。检索后还要通过方法学信号门槛；没有高价值候选时允许为空。
1. Trial designs for assessing induction, maintenance and other treatment effects on a continuous endpoint.
主题：临床试验方法与统计实践
相关性分数：7
期刊：Journal of biopharmaceutical statistics
公开日期：2026-09-22（电子公开）
期刊卷期日期：2026-Sep-22
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。
A pivotal clinical trial designed to demonstrate the benefit of a new treatment for treating a chronic disease usually has multiple objectives of affirming that the treatment is an appropriate induction, maintenance and long-term therapy. To fulfill some of these and other objectives for the trial, various designs have been applied. They include the active treatment lead-in followed by randomized maintenance design, the randomized induction followed by re-randomized withdrawal maintenance design, and the treat-through design. A sequential parallel comparison design (SPCD) has also been proposed for a trial with a binary endpoint. This SPCD can be treated as a hybrid of the above three designs and has some additional advantages. As the model and method for data analysis heavily depend on the type of endpoint, in this paper, we extend the application of the SPCD to a trial with a continuous endpoint. To fully utilize all available data of the induction and maintenance phases for an overall treatment effect evaluation, we consider a weighted combination test for an overall treatment effect assessment which incorporates the correlations of the components. Further, approaches for handling missing data are discussed. Simulations are conducted to evaluate the performances of the methods, and an example is used to illustrate the application of the methods.
2. Regimen-stratified Bayesian model-based meta-analysis of targeted biologics in generalised myasthenia gravis: efficacy comparison, mechanism-level class contrast, and endpoint sensitivity with model-informed trial design.
主题：临床试验方法与统计实践
相关性分数：6
期刊：Naunyn-Schmiedeberg’s archives of pharmacology
公开日期：2026-09-22（电子公开）
期刊卷期日期：2026-Sep-22
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。
Nine targeted biologics spanning four mechanisms have reached phase III development for generalised myasthenia gravis, yet no cross-programme comparison accounts for the distinct continuous versus cyclical dosing patterns or integrates both patient-reported (MG-ADL) and clinician-assessed (QMG) scales. We performed a regimen-stratified Bayesian model-based meta-analysis (MBMA) to compare efficacy, evaluate mechanism-level class differences, and inform trial design. Longitudinal MG-ADL and QMG data were extracted from nine placebo-controlled phase III trials. Six hierarchical nonlinear Emax models were fitted with inverse-variance weighting. Drug-specific maximum efficacy, net benefit over placebo, week 26 predictions, time to the minimum clinically important difference (MCID), cumulative efficacy, ranking probabilities, and mechanism-level class contrasts were derived. Robustness was assessed via model comparison, prior sensitivity, and Leave-one-study-out analyses on both scales. Endpoint-sensitivity simulation and a treatment-selection framework were appended. The study was registered with PROSPERO: CRD420261288549. On MG-ADL, zilucoplan led with the highest Emax (4.8 points; 95% CrI: 4.2-5.4) and largest net benefit (2.5; 2.0-3.1). On QMG, batoclimab led (Emax 5.9; 4.4-9.5; net benefit 4.1; 2.7-7.7). Efgartigimod achieved the fastest onset on both scales (≤ 1.6 weeks). At the mechanism class level, neonatal Fc receptor (FcRn) inhibitors demonstrated decisive superiority over complement inhibitors on QMG (mean Emax 5.28 vs 3.99; posterior probability 99.7%) while no class difference was observed on MG-ADL (52.5%), identifying a scale-dependent mechanism-efficacy dissociation. The regimen-stratified architecture was decisively favoured over a pooled model (Δ Expected log pointwise predictive density [ELPD] = + 19.8). Drug rankings were invariant across prior specifications and Leave-one-study-out permutations on both scales (maximum rank shift: 1 position). For rozanolixizumab on MG-ADL, snapshot week 26 endpoints were underpowered (65%); integrated endpoints recovered power to 94-95%. In the treatment-selection framework, batoclimab held the highest composite score in all eight priority profiles, while the identity of the runner-up varied with clinical priority. This analysis identifies a novel scale-dependent mechanism-level class effect - FcRn inhibitors outperform complement blockade on objective motor endpoints with near-certainty, while both classes improve patient-reported function equally. Across the multi dimensional treatment-selection framework integrating efficacy, safety, tolerability, and convenience, batoclimab emerged as the highest-ranked agent in all eight clinical priority profiles. These findings provide a pharmacodynamic evidence base for mechanism-guided treatment individualisation and endpoint optimisation in generalised myasthenia gravis.
3. 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.
4. 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.
5. 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.
6. The CLTI Paradigm Shift: Implications for Clinical Trial Design and Endpoints in Endovascular Management of Infrapopliteal Disease.
主题：临床试验方法与统计实践
相关性分数：6
期刊：Journal of endovascular therapy : an official journal of the International Society of Endovascular Specialists
公开日期：2025-08-28（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。
The evolution from critical limb ischemia to chronic limb-threatening ischemia (CLTI) necessitates a reevaluation of clinical trial endpoints. Traditional measures like hemodynamic indices and lesion patency inadequately reflect CLTI complexity or patient-centered outcomes. This article explores the limitations of conventional endpoints and proposes a modified definition of clinically-driven target lesion (TL) revascularization (CD-TLR) that addresses inflow, TL, and outflow disease. By incorporating a more comprehensive assessment of vascular health and prioritizing patient-relevant outcomes, this modified CD-TLR definition may better reflect modern CLTI management strategies and improve clinical relevance of trial results in this challenging patient population.Clinical ImpactThe evolution from CLI to CLTI requires reassessing how we measure treatment success in clinical trials. This review identifies why traditional endpoints like hemodynamic indices, lesion patency, and CD-TLR may not adequately inform clinical decision-making. The importance of measuring outcomes that directly impact patient quality of life will help clinicians better evaluate and apply clinical trial results. An emphasis on limb salvage, wound healing, and functional outcomes, rather than surrogate endpoints alone, will lead to more informed treatment decisions and improved CLTI management strategies.
7. 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.
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. 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.
10. Optimising clinical trial design choices in inflammatory bowel disease.
主题：临床试验方法与统计实践
相关性分数：4
期刊：BMJ open gastroenterology
公开日期：2026-09-22（电子公开）
期刊卷期日期：2026-Sep-22
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 success of inflammatory bowel disease (IBD) clinical trials is strongly influenced by study design and disease-specific operational challenges. Over the past decade, however, IBD clinical trials face slow enrolment, poor retention, accumulating costs and limited representativeness. Trials are further constrained by protocol and operational complexity, financial pressures and regulatory requirements. Carefully selected and optimised trial designs may address the inherent challenges of IBD research and should take into account the patient profiles under investigation, mode of action and speed of onset of effect of the investigational product, among other factors. This narrative review discusses four key study design strategies for IBD clinical trials, including treat-through maintenance, responder re-randomisation, Master Protocol approaches (basket, umbrella and platform trials) and Bayesian methodologies. Treat-through maintenance designs are effective at evaluating sustained efficacy and real-world durability, whereas responder re-randomisation approaches are widely used in drug registration programmes to distinguish induction and maintenance effects for regulator clarity. Master Protocol designs may improve efficiency and reduce placebo exposure, while trials using Bayesian methodologies can strengthen interpretation of efficacy and safety outcomes, particularly in early-phase or complex studies. Key considerations within protocols include the use of co-primary endpoints, selection of secondary/exploratory endpoints, control group design and integrating digital health technologies, among others. Strategic application of innovative methodologies can improve trial delivery and enhance data robustness and interpretability, thus supporting more efficient development of effective therapies for patients with IBD.
11. Comparison of Silevimig, a Novel Bispecific Anti-Rabies Monoclonal Antibody, with Human Rabies Immunoglobulin for Post-Exposure Prophylaxis: A Phase III, Randomized, Double-Blind, Non-Inferiority Trial.
主题：临床试验方法与统计实践
相关性分数：4
期刊：Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
公开日期：2026-09-21（电子公开）
期刊卷期日期：2026-Sep-21
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。
This phase III randomized, double-blind, non-inferiority trial evaluated Silevimig, a bispecific anti-rabies monoclonal antibody targeting antigenic sites I and III, as a substitute for human rabies immunoglobulin (HRIG) in post-exposure prophylaxis. Adults (>18 years) with suspected WHO category III rabies exposure were randomly assigned (3:1) to receive Silevimig or HRIG. After wound cleansing, the study drug was administered on day 0, together with a rabies vaccine given on days 0, 3, 7, 14, and 28. The co-primary endpoints were the adjusted geometric mean concentration (GMC) of rabies virus-neutralizing antibodies (RVNAs) on day 7, the proportion of participants with an RVNA level of ≥ 0.5 IU/mL (seroresponse) by day 14, and the rabies-free survival rate in 1 year (D365). Safety was assessed through adverse events (AEs) and serious adverse events (SAEs). A total of 1,200 participants were enrolled. On day 7, the adjusted GMC of RVNAs was 0.40 IU/mL in the Silevimig group versus 0.36 IU/mL in the HRIG group, meeting the non-inferiority criterion (ratio 1.11; 95% CI: 1.01-1.21). Seroresponse rates on days 14 and 90 were slightly higher with Silevimig. No rabies cases occurred during the 1-year follow-up, yielding a 100% rabies-free survival rate in both groups. Most AEs were mild to moderate. Silevimig was non-inferior to HRIG in inducing early RVNA responses, was well tolerated, and did not interfere with vaccine-induced immunity. These findings support Silevimig as a safe and effective alternative for passive rabies post-exposure prophylaxis (ClinicalTrials, NCT05846568).
12. Clinical and economic impact of bivalent respiratory syncytial virus prefusion F (RSVpreF) vaccination in older adults: a cost-effectiveness analysis for Chile.
主题：因果推断、RWE 与卫生经济学
相关性分数：4
期刊：Expert review of vaccines
公开日期：2026-09-12（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: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract disease in older adults in Chile. Chile’s National Immunization Technical Advisory Group (NITAG) recommended RSV vaccination for adults aged ≥60 years with risk factors for severe illness. This study estimated the cost-effectiveness of bivalent RSVpreF vaccination among at-risk older adults in Chile.
RESEARCH DESIGN AND METHODS: A population-based Markov model projected RSV-related outcomes under no vaccination and RSVpreF vaccination over the cohort lifetime. Cost-effectiveness was assessed from healthcare and societal perspectives in 2025 Chilean Pesos (CLP) and US Dollars (US$), with costs and outcomes discounted at 3% annually. Sensitivity analyses tested the model robustness.
RESULTS: RSVpreF vaccination was projected to prevent 14,956 hospitalizations, 50,419 emergency department visits, and 124,849 physician office visits; avert CLP76 billion (US$82 million) in direct medical costs and CLP305 billion (US$328 million) in indirect costs; and generate 7,079 quality-adjusted life-years (QALYs). At a threshold of CLP15,977,348 (US$17,180) per QALY gained, the maximum cost-effective vaccine price was CLP100,480 (US$108) and CLP265,261 (US$285) from the healthcare and societal perspectives respectively.
CONCLUSIONS: RSVpreF vaccination would reduce RSV burden and likely be cost-effective for older adults in Chile.
13. 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.
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. Expert consensus on clinical trial design guidelines for FLASH radiotherapy.
主题：临床试验方法与统计实践
相关性分数：3
期刊：Precision radiation oncology
公开日期：2026-09-23（电子公开）
期刊卷期日期：2026-Sep-23
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。
In recent years, ultra-high dose-rate FLASH radiotherapy (FLASH-RT) has emerged as a prominent research focus in radiation oncology. A series of preclinical data indicate that FLASH-RT can achieve tumor-killing efficacy that is not inferior to that of conventional radiotherapy (CONV-RT) while significantly reducing radiation damage to normal tissues. This distinctive tissue-sparing effect is known as the “FLASH effect.” Rapid progress has been made in the clinical translation and application of FLASH-RT. Against this backdrop, the China Anti-Cancer Association Radiation Oncology Committee and the Chinese Medical Doctor Association Radiation Oncology Physician Committee gathered a group of experts and compiled the “Expert Consensus on Clinical Trial Design Guidelines for FLASH Radiotherapy” based on the latest domestic and international research advancements. This document summarizes the latest advances in FLASH-RT and offers practical guidance for its design and translational application in future clinical trials.
18. Young adult polysubstance use trajectories and later non-prescribed opioid use and drug use disorder symptoms: A propensity score-matched analysis.
主题：因果推断、RWE 与卫生经济学
相关性分数：3
期刊：Drug and alcohol dependence reports
公开日期：2026-09-12（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: Longitudinal patterns of common substance use in young adulthood may identify risk for later opioid-related and other drug-related harm. We examined whether longitudinal trajectories of alcohol, cannabis, and nicotine use during young adulthood were associated with non-prescribed opioid use and other drug use disorder (ODUD) symptoms in adulthood.
METHODS: We analyzed restricted longitudinal Monitoring the Future panel data from 26 baseline cohorts (1976-2002). Group-based trajectory modeling identified polysubstance use trajectories from baseline through the first three biennial follow-ups. Trajectories were classified as low-use or high-use. Outcomes were any non-prescribed opioid use and ODUD symptoms between ages 35 and 55. Propensity score weighting estimated associations under average treatment effect for the treated, average treatment effect for the untreated, and average treatment effect estimands.
RESULTS: Five trajectory groups were identified and classified as low-use or high-use. The low-use trajectory included 14.7% of participants and was characterized by no cannabis or nicotine use and low-to-moderate alcohol use; the remaining trajectories involved high use of at least one substance. In average treatment effect models, high-use trajectory membership was associated with higher odds of later non-prescribed opioid use (OR=3.61; 95% CI: 3.34, 3.91) and ODUD symptoms (OR=15.9; 95% CI: 13.5, 18.8).
CONCLUSION: In this US national longitudinal cohort, young adults with sustained high use of alcohol, cannabis, and/or nicotine had higher odds of non-prescribed opioid use and ODUD symptoms later in adulthood. These findings support targeted prevention, harm reduction, and cessation efforts addressing polysubstance use among young adults.
19. Virological and metabolic outcomes after switching to dolutegravir or rilpivirine in virologically suppressed adults with HIV in Thailand: an open-label, randomised, controlled, non-inferiority trial.
主题：临床试验方法与统计实践
相关性分数：3
期刊：The Lancet regional health. Southeast Asia
公开日期：2026-09-15（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: Dolutegravir (DTG)-based antiretroviral therapy is widely recommended; however, weight gain and metabolic effects remain a concern. Rilpivirine (RPV) is a potential switch option for virologically suppressed individuals with HIV receiving efavirenz (EFV)-based treatment. We aimed to compare the virological and metabolic outcomes after switching from TDF/FTC/EFV to TDF/3TC/DTG or TDF/FTC plus RPV.
METHODS: In this randomised, open-label, parallel-group, non-inferiority trial at Maharat Nakhon Ratchasima Hospital, Thailand, adults with HIV-1 RNA below 50 copies per mL for at least 6 months on TDF/FTC/EFV were randomly assigned 1:1 to once-daily TDF/3TC/DTG or TDF/FTC plus RPV. The primary outcome was virological non-suppression, defined as HIV-1 RNA 50 copies per mL or higher at week 48. Non-inferiority of RPV was concluded if the lower bound of the 95% CI for the risk difference (DTG minus RPV) was greater than -8 percentage points. Secondary outcome included changing in body weight, LDL cholesterol, HbA1c, and estimated glomerular filtration rate (eGFR) over 48 weeks. This study was registered with the Thai Clinical Trial Registry (TCTR20211229003).
FINDINGS: Between March 2022 and November 2023, 267 participants were randomly assigned to receive DTG (n = 133) or RPV (n = 134). In the per-protocol population, virological non-suppression occurred in three (3%) of 118 participants in the DTG group and five (4%) of 122 participants in the RPV group (risk difference -1.56%, 95% CI -6.08 to 2.97). Non-inferiority of RPV was demonstrated in all prespecified analysis populations using the -8% margin. Weight gain was greater with RPV than with DTG (2.3 kg vs. 1.4 kg; p = 0.035). LDL cholesterol decreased in both groups without significant between-group differences, while eGFR declined more in the DTG group.
INTERPRETATION: Switching to RPV was non-inferior to DTG for virological outcomes at 48 weeks. RPV represents an alternative for patients in whom DTG is unsuitable or not preferred. Although between-group differences in metabolic outcomes and weight gain were minimal, larger, longer-term trials are warranted to confirm these findings.
FUNDING: This work was supported by The Royal College of Physicians of Thailand, (to R.K.). APC fee was supported by Faculty of Tropical Medicine, Mahidol University and Mahidol University (to T.N.).
20. Tegileridine vs. sufentanil for postoperative analgesia in general surgery: A prospective, randomized, controlled, non-inferiority trial.
主题：临床试验方法与统计实践
相关性分数：3
期刊：British journal of clinical pharmacology
公开日期：2026-09-20（电子公开）
期刊卷期日期：2026-Sep-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。
OBJECTIVE: Tegileridine, a novel G protein-biassed μ-opioid receptor agonist, may offer effective postoperative analgesia with fewer opioid-related adverse effects. This study evaluated its analgesic efficacy, safety and impact on surgical stress response vs. sufentanil for patient-controlled intravenous analgesia (PCIA) in general surgery patients.
METHODS: In this single-centre, double-blind, non-inferiority trial, 120 adults scheduled for elective laparoscopic cholecystectomy, appendectomy or inguinal hernia repair were randomized 1:1 to 48-h PCIA with tegileridine (5 mg) or sufentanil (200 μg), both with tropisetron 10 mg. The primary outcome was 24-h area under the curve (AUC) for resting visual analogue scale (VAS) pain scores, with a non-inferiority margin of 10.6 points·h. Secondary outcomes included pain scores, PCIA usage, adverse events, recovery and plasma cortisol and interleukin-6 (IL-6).
RESULTS: All 120 patients completed the study. Mean 24-h resting VAS-AUC was 102.3 ± 25.6 points·h (tegileridine) vs. 105.8 ± 27.1 points·h (sufentanil). Upper 97.5% confidence limit for the difference was 9.8 points·h, below the 10.6 margin (p < .001). Tegileridine significantly reduced postoperative nausea and vomiting (p = .007) and accelerated gastrointestinal recovery (p < .001). Postoperative cortisol and IL-6 elevations were significantly attenuated at 6 and 24 h (p < .001). No significant differences were observed for other adverse events or satisfaction.
CONCLUSION: Tegileridine provides non-inferior analgesia to sufentanil FOR PCIA after general surgery, with reduced PONV, faster gastrointestinal recovery and blunted stress response, supporting its potential role in enhanced recovery protocols.
TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2500114360).