方法与临床研究雷达（2026-10-28）
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1. 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.
2. Evolution of disease modifying therapy clinical trial design and therapeutic endpoints for Parkinson’s disease.
主题：临床试验方法与统计实践
相关性分数：6
期刊：Journal of Parkinson’s disease
公开日期：2026-02-08（电子公开）
期刊卷期日期：2026-Nov
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
The traditional approach of using double-blind, placebo controlled, parallel group trial designs has confirmed the efficacy of a large number of agents in relieving the symptoms of Parkinson’s disease (PD) but has not, to date, led to the discovery of any disease-modifying treatments for PD. There are multiple potential reasons underlying the failure to find disease modifying approaches, which may in part relate to; inadequate understanding of PD pathophysiology and therefore inappropriate target selection; the possibility that even good candidate drugs may simply fail to reach and to ultimately engage with their putative targets at the required dose; and the significant heterogeneity of the disease both in terms of its pathophysiology and its motor and non-motor symptoms. PD also has some additional challenges that may be addressed by careful consideration of trial design. This includes; its generally slow rate of disease progression necessitating long follow-up times to identify evidence of disease slowing; lack of understanding regarding the optimal stage of disease that might be most amenable to intervention; as well as lack of consensus regarding which outcome measures best capture patient relevant disease progression, and which biomarkers might consistently and objectively provide the earliest indication of disease progression. In this review we will discuss these issues and potential approaches that may help in the evolution of clinical trial design and thus ultimately provide a pathway to increase the likelihood of successful identification of disease-modifying treatments for Parkinson’s disease.
We have not yet discovered any medications or other interventions that slow down the progression of Parkinson’s disease. This may be partly because we have tested the wrong medications in the wrong people but may also be due to the way in which we design and carry out clinical trials. In this article, we will discuss these issues and highlight the strategies that are being set up to try and improve our chances of success.
3. Cost-effectiveness of early versus delayed disease-modifying antirheumatic drugs for psoriatic arthritis.
主题：因果推断、RWE 与卫生经济学
相关性分数：5
期刊：Lancet regional health. Americas
公开日期：2026-10-14（电子公开）
期刊卷期日期：2027-Jan
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: Disease-modifying antirheumatic drugs (DMARDs) are standard first-line therapy for psoriatic arthritis (PsA). Observational studies suggest earlier initiation is associated with superior minimal disease activity (MDA) attainment, yet the economic and health implications of treatment timing remain uncertain. This cost-utility analysis evaluated the cost-effectiveness of early versus delayed DMARD initiation in DMARD-naive adults with PsA from a U.S. payer perspective.
METHODS: We built a cohort state-transition (Markov) model (monthly cycles, 15-year horizon) from published data (2000-2025). Patients initiated a DMARD under two strategies: early (≤1 year post-diagnosis) and delayed initiation (>1 year). Patients remained in the pre-treatment state for six months prior to response assignment, then transitioned among complete response (sustained MDA), partial response (non-sustained MDA), non-response, no treatment, and death. Primary outcomes included the incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit (INMB). Uncertainty intervals (UIs) were derived from probabilistic sensitivity analyses.
FINDINGS: Early DMARD initiation provided an additional 0.56 (95% UI, 0.32-0.83) QALYs at an incremental cost of -US$43,902.94 (95% UI, -US$147,096.29 to US$61,615.86) per patient relative to delayed initiation, yielding a favourable ICER (-US$78,398.11/QALY). At a willingness-to-pay threshold of US$50,000/QALY, mean INMB was US$71,902.94 (95% UI, -US$36,663.51 to US$176,658.91), with early initiation preferred in 90.6% of simulations.
INTERPRETATION: Early DMARD initiation was associated with improved long-term health outcomes at reduced costs, suggesting timely DMARD initiation may represent a high-value strategy. Given the observational basis of the key treatment-timing input, findings support disease-duration stratified analyses of existing phase III trials and further characterization of access delays.
FUNDING: None.
4. Statistical analysis plan for transfusion of modified whole blood versus blood components therapy in patients with severe trauma: randomized controlled trial - WEBSTER trial.
主题：临床试验方法与统计实践
相关性分数：5
期刊：Critical care science
公开日期：2026-10-16（电子公开）
期刊卷期日期：2026
内容状态：待评估
为什么值得看：包含可供初筛的摘要；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: Hemostatic resuscitation with modified whole blood is an alternative to balanced blood-component therapy for trauma patients with hemorrhagic shock, with potential efficacy and logistical advantages. The WEBSTER trial was designed to compare these interventions in patients with trauma hemorrhagic shock.
METHODS: Single-center, open-label, parallel-group randomized clinical trial comparing whole blood with blood components in adults with trauma hemorrhagic shock.
PRIMARY OUTCOME: hierarchical composite of all-cause 28-day mortality and SOFA score during the first 5 days after randomization. We will estimate treatment effects using a win-ratio analysis that prioritizes mortality. Primary analysis follows the intention-to-treat principle; secondary analyses in as-treated and per-protocol populations are planned. Secondary outcomes include mortality at additional time points, organ dysfunction metrics, coagulation parameters, transfusion requirements, and adverse events.
RESULTS: Primary outcome analyses will report win ratios, and secondary outcomes will be analyzed with hypothesis tests or regression time-to-event models; 95% confidence intervals will accompany all estimates. We do not plan formal adjustment for multiplicity because the outcomes share the same underlying construct. All outcomes will be interpreted in the context of the overall pattern of results.
CONCLUSION: This statistical analysis plan prespecifies transparent methods to assess the effect of whole blood versus blood-component therapy in trauma patients. The hierarchical framework, complementary sensitivity analyses and comprehensive interpretation are intended to provide a robust and clinically meaningful assessment of whole blood effects.
5. Bolus-only versus bolus plus continuous infusion hydromorphone for refractory cancer pain: a prospective, multicenter, randomized noninferiority trial.
主题：临床试验方法与统计实践
相关性分数：5
期刊：Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
公开日期：2026-10-22（电子公开）
期刊卷期日期：2026-Oct-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。
INTRODUCTION: Refractory cancer pain (RCP) remains difficult to manage despite guideline-based therapy. Patient-controlled intravenous analgesia (PCIA) is increasingly used, yet the optimal administration mode remains unclear.
METHODS: In this prospective, multicenter, randomized, non-inferiority trial, patients with refractory cancer pain were enrolled between December 1, 2018, and August 31, 2022, and randomly assigned to either a bolus-only PCIA group (Group B) or a bolus plus continuous infusion group (Group BC). Pain intensity was assessed using the Numerical Rating Scale (NRS). The primary endpoint was the pain relief rate at 72 h after PCIA initiation, defined as the proportion of patients achieving a ≥ 50% reduction in resting pain intensity from baseline. Non-inferiority was evaluated using the 90% confidence interval (CI) for the between-group difference, with a predefined non-inferiority margin of - 10%.
RESULTS: A total of 226 patients were randomized. with 104 assigned to Group B and 111 to Group BC. Both groups showed significant reductions in resting NRS scores and breakthrough cancer pain (BTcP) NRS scores from T1 to T6 compared with baseline (all P < 0.05). At 72 h, the pain relief rate was 89.4% in Group B and 94.2% in Group BC. The between-group difference yielded a 90% CI of - 11.2% to 1.1%, which crossed the predefined non-inferiority margin. Therefore, non-inferiority of Group B compared with Group BC was not demonstrated. The incidence of PCIA-related adverse events was comparable between the two groups.
CONCLUSION: Non-inferiority of bolus-only PCIA compared with bolus plus continuous infusion was not established. Nevertheless, both PCIA administration modes provided effective analgesia and demonstrated favorable safety profiles in patients with refractory cancer pain.
CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800020014. Registered 19 November 2018, https://www.chictr.org.cn/showprojEN.html?proj=32731.
6. 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.
7. Understanding calibration robustness under extreme spectral multicollinearity: A systematic evaluation of high-dimensional NIR spectroscopy.
主题：统计建模与试验设计方法
相关性分数：5
期刊：Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy
公开日期：2026-09-24（电子公开）
期刊卷期日期：2027-Feb-05
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。
High-dimensional near-infrared (NIR) spectroscopy datasets are characterized by strong wavelength correlation, limited sample sizes, and structured experimental variability, creating significant challenges for multivariate calibration. Under these conditions, extreme multicollinearity can lead to unstable regression coefficients, inflated estimator variance, and reduced model robustness. Although numerous calibration algorithms have been proposed, comparatively little attention has been devoted to understanding how multicollinearity influences calibration behaviour across different modelling paradigms. This study systematically investigates the performance of classical chemometric, regularized linear, dimensionality reduction, wavelength selection, and nonlinear machine learning approaches using a publicly available glucose NIR spectroscopy dataset comprising 4200 wavelength variables and structured experimental perturbations. Partial Least Squares (PLS), Ridge Regression, Elastic Net, Principal Component Analysis (PCA), Genetic Algorithm-based PLS (GA-PLS), Artificial Neural Networks (ANN), Support Vector Regression (SVR), Random Forest, Gradient Boosting, and Gaussian Process Regression were evaluated using repeated cross-validation and independent validation. Model assessment was complemented by multicollinearity diagnostics, residual analysis, and wavelength-selection stability analysis to investigate the mechanisms governing calibration robustness. SNV-PLS achieved the best overall predictive performance on the independent validation dataset (RMSE = 5.75 mM; R2 = 0.864), followed by GA-PLS (RMSE = 5.82 mM; R2 = 0.861) and SNV-Ridge (RMSE = 5.84 mM; R2 = 0.860), while SNV-Elastic Net achieved comparable performance (RMSE = 5.93 mM; R2 = 0.856). GA-PLS reduced the spectral dimensionality from 4200 to 50 wavelengths; however, repeated GA runs showed only 0-2% exact wavelength overlap, increasing to 17-29% within ±5 nm and 30-47% within ±10 nm, indicating regional rather than exact-wavelength stability. Variance Inflation Factor analysis revealed extreme predictor collinearity, while residual and domain-coverage analysis showed that the major validation deterioration was localized at 50 mM glucose, where the six validation samples were systematically underpredicted and originated from an experimental condition absent from the calibration set. The findings suggest that effective management of covariance structure and estimator variance may be more influential than increasing model complexity for the investigated high-dimensional NIR calibration problem. These results provide practical guidance for selecting robust and interpretable calibration strategies for high-dimensional spectroscopic applications affected by severe multicollinearity.
8. 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.
9. 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.
10. A flexible threshold biomarker trial design for treatment intensification and de-intensification.
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：2026-10-27（电子公开）
期刊卷期日期：2026-Oct-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: In Oncology, prognostic biomarkers are commonly used to tailor treatment intensity to a patient’s risk of disease progression. Several recent Phase III trials embed two studies within one protocol, comparing standard versus de-intensified therapy in good-prognosis patients and intensified versus standard therapy in poor-prognosis patients, using a single fixed biomarker threshold to classify patients into good and poor prognosis. Such designs are clinically intuitive but rely on a prespecified cut-point for which there can be substantial uncertainty as to the optimal value.
METHODS: We propose a flexible threshold, biomarker-based design in which patients with intermediate biomarker values are randomized to three arms (control, de-intensified, intensified), while those at the extremes are randomized between control and de-intensified therapy (low biomarker) or intensified (high biomarker). The design jointly tests non-inferiority of de-intensified therapy in lower-risk patients and superiority of intensified therapy in higher-risk patients, while estimating the optimal biomarker thresholds. Family-wise Type I error is controlled through a two-stage bootstrap testing procedure.
RESULTS: In simulation settings where the alternative non-inferiority and superiority hypotheses hold over broad overlapping biomarker regions, the proposed flexible threshold biomarker design has greater power than a fixed threshold design while maintaining appropriate Type I error control. When the optimal decision rule matches the prespecified fixed cutoff, the two designs perform similarly. This reflects a bias-variance trade-off, in which fixed threshold designs perform well when the cutoff is correctly specified, whereas the flexible threshold biomarker design is more robust when the optimal threshold is uncertain or misspecified.
CONCLUSIONS: The proposed flexible threshold biomarker design offers a robust and efficient framework for trials seeking to tailor treatment intensity using a prognostic biomarker. The approach is broadly applicable to other diseases in which both escalation and de-escalation of therapy are of clinical interest and there is clinical equipoise among the three treatment options for patients with intermediate biomarker values.
11. Statistical analysis plan for a stepped-wedge cluster randomized clinical trial for the evaluation of the clinical impact of different telemedicine practices in intensive care units - TELESCOPE 2 trial.
主题：临床试验方法与统计实践
相关性分数：4
期刊：Critical care science
公开日期：2026-10-16（电子公开）
期刊卷期日期：2026
内容状态：待评估
为什么值得看：包含可供初筛的摘要；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 optimal model for delivering Tele-ICU is still to be determined. In the TELE-critical Care verSus usual Care on ICU Performance (TELESCOPE) trial, implementing medical-led daily multidisciplinary rounds did not show evidence of improved clinical outcomes. The TELESCOPE 2 trial was therefore designed to evaluate whether expanding this model to include a structured multidisciplinary care bundle, along with a formalized quality and safety management framework, would translate process improvements into measurable patient-centered outcome benefits.
OBJECTIVE: To evaluate whether a structured Tele-ICU intervention, comprising intensivist-led daily multidisciplinary rounds, a multidisciplinary care bundle (nursing, physical therapy, pharmacy), and a quality and safety management package, can reduce intensive care unit length of stay in Brazilian public intensive care units.
METHODS: TELESCOPE 2 is a multicenter, open-label, stepped-wedge cluster randomized trial including 25 intensive care units in Brazil from January 2024 to January 2026. Intensive care units are randomized to five sequences, receiving the intervention at staggered times. All adult patients admitted to participating units are eligible, except those admitted for non-medical reasons or those previously included in the study. The multifaceted telemedicine intervention comprises: i) daily multidisciplinary rounds led by board-certified intensivists; ii) coordinated care by a multidisciplinary team; and iii) a management strategy focused on quality improvement and patient safety. The primary outcome is intensive care unit length of stay. Secondary outcomes include clinical endpoints (mortality, ventilator-free days at 28 days, and ventilator-associated events), process-of-care indicators (mobilization, head-of-bed elevation, and sedation management), and unit-level organizational outcomes.
CONCLUSION: We describe the statistical analysis plan for the TELESCOPE 2 trial, finalized prior to database lock. This pre-specified approach mitigates analysis bias and ensures the transparency and robustness of the reported results.
12. Evaluating a multi-vaccine respiratory immunization strategy involving SARS-CoV-2, pneumococcal, and influenza vaccines in adults: A randomized, open-label, multicenter, controlled, non-inferiority Phase IV trial in China.
主题：临床试验方法与统计实践
相关性分数：4
期刊：Human vaccines & immunotherapeutics
公开日期：2026-10-21（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。
Co-administration of vaccines targeting multiple respiratory pathogens may enhance coverage and streamline adult immunization programs. We conducted a randomized, multicentre, open-label Phase IV trial registered at Chinese Clinical Trial Registry (ChiCTR2100046227) in China to evaluate the immunogenicity and safety of co-administering an inactivated SARS-CoV-2 vaccine (WIBP-CorV) with the 23-valent pneumococcal polysaccharide vaccine (PPV23) and a quadrivalent inactivated influenza vaccine (IIV4). A total of 1,404 adults aged ≥ 18 year, including equal numbers of adults aged 18-59 year and ≥60 year, were randomized 1:1:1 to receive WIBP-CorV + PPV23 on Day 0 followed by WIBP-CorV + IIV4 on Day 28, WIBP-CorV alone on Days 0 and 28, or PPV23 on Day 0 followed by IIV4 on Day 28. Co-administration preserved humoral immune responses across vaccine platforms. Non-inferiority in geometric mean titers or concentrations was demonstrated for SARS-CoV-2 neutralizing antibodies and pneumococcal serotype-specific IgG responses. Seroconversion rates were non-inferior to those following separate administration for all pneumococcal serotypes, though results were less consistent for SARS-CoV-2 (after the second dose) and influenza A(H1N1). Age-stratified analyses showed age- and strain-specific non-inferiority findings that should be interpreted cautiously. Co-administration demonstrated an acceptable safety profile, with only slightly higher rates of mild, transient local reactions and no vaccine-related serious adverse events (SAEs). These findings support the feasibility of co-administering WIBP-CorV with PPV23 and IIV4 while maintaining immunogenicity and safety in adults represented in this study.Trial registration The study was registered in the Chinese Clinical Trial Registry (ChiCTR) under registration number ChiCTR2100046227.
A Phase IV trial evaluated co-administration of COVID-19, PPV23 and IIV4.Co-administration preserved immunogenicity across multiple vaccine platforms.Non-inferiority was achieved for most predefined immunogenicity endpoints.No vaccine-related serious adverse events were observed.Findings support integrated adult respiratory vaccination strategies.
13. Cost-effectiveness of universal infant hepatitis B vaccination programme in Finland.
主题：因果推断、RWE 与卫生经济学
相关性分数：4
期刊：Vaccine
公开日期：2026-10-16（电子公开）
期刊卷期日期：2026-Dec-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。
OBJECTIVES: To evaluate the cost-effectiveness of a universal infant hepatitis B vaccination programme in Finland.
METHODS: A static cohort model was employed to compare the health care costs and health effects of a universal infant hepatitis B vaccination programme with the present targeted vaccination programme. Estimates of hepatitis B incidence and hepatitis B-related costs were derived from national register data. The estimated hepatitis B incidence took into account acute asymptomatic infections. An annual discount rate of 3% was applied to costs and health effects and the main outcome measure was cost per quality adjusted life year (QALY) gained. We present the results with different price differences per dose of hexavalent and pentavalent vaccines. Sensitivity analyses identified influential inputs in the cost-effectiveness analysis.
RESULTS: We estimated 41 acute cases with every fifth being symptomatic, three chronic hepatitis B cases, and three hepatitis B-related deaths in a birth cohort of 58,000 children. The corresponding health care costs were ϵ46,400 and QALYs lost 14.4. The incremental cost-effectiveness ratios (ICER) were between ϵ24,500 and ϵ162,900 when the price difference per dose of pentavalent versus hexavalent vaccine was between two and 12 euros. The results were sensitive to hepatitis B incidence, vaccine cost, and discount rate.
CONCLUSIONS: In a very low hepatitis B prevalence country such as Finland, a universal infant hepatitis B vaccination programme appears justifiable use of public health care resources only with a very small price difference between pentavalent and hexavalent vaccines.
14. Low-intensity versus medium-intensity continuous renal replacement therapy for critically ill patients (LIMIT) trial: Protocol summary and statistical analysis plan of a randomised clinical trial.
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：2026-09-28（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。
BACKGROUND: Severe acute kidney injury in critically ill patients may require continuous renal replacement therapy (CRRT), yet mortality remains high. A standard CRRT intensity is 20-25 mL/kg/hr, because higher doses have not improved outcomes. Excessive treatment may cause harm by removing antibiotics and other essential substances and potentially impairing renal recovery. Observational data suggest that lower-intensity CRRT may be effective, warranting a clinical trial to compare low-versus standard-intensity therapy.
OBJECTIVE: The objective of this study was to describe the prespecified protocol and the statistical analysis plan of the low-intensity versus medium-intensity continuous renal replacement therapy for critically Ill patients (LIMIT) trial.
DESIGN SETTING PARTICIPANTS AND INTERVENTIONS: The LIMIT trial is an investigator-initiated, multicentre, open-label, randomised clinical trial, with a target sample size of 400 participants. The trial compares low-intensity CRRT (12 mL/kg/hr) and medium-intensity CRRT (25 mL/kg/hr) in adult patients with acute kidney injury requiring CRRT in the participating intensive care units.
MAIN OUTCOME MEASURES: The primary outcome is a hierarchical composite of survival and time to successful liberation from RRT through day 28 from randomisation, analysed using a win-ratio. Secondary outcomes include intensive care unit mortality, hospital mortality, dialysis dependence at hospital discharge among survivors, vasopressor-free days at day 28, and ventilator-free days at day 28.
CONCLUSION: The LIMIT trial will evaluate the effect of low-intensity CRRT on mortality and time to successful liberation from RRT compared with medium-intensity CRRT in adults with acute kidney injury. Its findings may also inform future research on broader patient-centred and societal implications of CRRT intensity.
15. 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.
16. 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.
17. Deep survival analysis for competing risk modeling with functional covariates and missing data imputation.
主题：生存与复杂事件结局方法
相关性分数：4
期刊：Neural networks : the official journal of the International Neural Network Society
公开日期：2026-07-27（电子公开）
期刊卷期日期：2027-Jan
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。
We introduce the Functional Competing Risk Net (FCRN), a unified deep-learning framework for discrete-time survival analysis under competing risks, which seamlessly integrates functional covariates and handles missing data within an end-to-end model. By combining an Adaptive Learnable Basis (ALB) micro-network for functional data representation and a gradient-based imputation module, FCRN simultaneously learns to impute missing values and predict event-specific hazards. Evaluated on multiple simulated datasets and a real-world ICU case study using the MIMIC-IV and Cleveland Clinic datasets, FCRN demonstrates substantial improvements in prediction accuracy over random survival forests and traditional competing risks models. This approach advances prognostic modeling in critical care by more effectively capturing dynamic risk factors and static predictors while accommodating irregular and incomplete data.
18. 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).
19. 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.
20. ADPKD as a Temporally Dynamic Disease: Implications for Biomarkers, Trial Design, and Therapeutic Targeting.
主题：临床试验方法与统计实践
相关性分数：3
期刊：Kidney international reports
公开日期：2026-09-26（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。
Autosomal dominant polycystic kidney disease (ADPKD) has traditionally been conceptualized as a structurally progressive disease, with cyst growth driving loss of kidney function. This view has led to the widespread use of total kidney volume for risk stratification and clinical trial design. However, longitudinal human studies and experimental models indicate that the relationship between structure, function, and underlying biology changes over the disease course. Earlier disease is characterized by prominent cystic, proliferative, and metabolic activity together with early inflammatory responses; inflammatory and injury-repair processes become increasingly prominent during intermediate disease, whereas fibrosis and loss of functional parenchyma assume a greater role later as kidney function declines. These processes overlap rather than define discrete stages, and their timing and relative contributions likely vary among individuals. This review proposes that ADPKD be considered as a temporally dynamic disease and examines the implications of this framework for biomarker development, clinical trial design, and therapeutic targeting. Such a framework emphasizes the need to complement structural measures with biomarkers of evolving biology, to identify biological transitions prospectively, and to align therapeutic targets and end points with the processes contributing meaningfully to progression in the population being studied.