方法与临床研究雷达（2026-11-07）
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1. Sample-size justification, differential post-randomization exclusion, and multiplicity in a randomized trial of epidural versus wound catheter analgesia after pancreatoduodenectomy.
主题：临床试验方法与统计实践
相关性分数：6
期刊：Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.]
公开日期：2026-09-09（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：暂缺摘要，需回到 PubMed 核验；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
2. Revisiting trial design considerations to improve efficiency of HIV-1 vertical transmission prevention efficacy trials in infants.
主题：临床试验方法与统计实践
相关性分数：5
期刊：Clinical trials (London, England)
公开日期：2026-11-01（电子公开）
期刊卷期日期：2026-Nov-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。
INTRODUCTION: While the global incidence of HIV-1 vertical transmission has reduced greatly, a persistent and unacceptable number of new infant infections continue to occur through breastfeeding. Long-acting antiretroviral agents, including injectable drugs and broadly neutralizing monoclonal antibodies, given as prophylaxis to infants hold great potential to eliminate HIV-1 transmission. However, given the low frequency of HIV-1 vertical transmission during breastfeeding in trial settings, efficient and innovative study designs will be necessary to evaluate the efficacy of agents administered to infants as prophylaxis.Key Design Considerations:We provide an overview of study design considerations and assess alternative specifications that may improve the efficiency of future trials to evaluate the efficacy of a novel agent administered to infants in preventing breastfeeding acquisition of HIV-1. We highlight key attributes of the study estimand (intervention, target population, outcomes and endpoints, intercurrent events, and population-level summaries) and discuss nuances in their specification with respect to improving efficiency. We explore alternatives to the classic randomized clinical trial framework, including augmented clinical trials that incorporate external data to supplement clinical trial data. We also provide an overview of Bayesian and transportability-based statistical analysis approaches for analyzing such augmented clinical trials. Modifications to the study design in the context of the estimand framework alone will not be sufficient to address challenges introduced by the low frequency of transmission events. Alternative study designs that incorporate external data are becoming increasingly acceptable and may help alleviate resource constraints.
CONCLUSION: A multi-faceted approach will be required to design efficacy trials for postnatal prophylaxis. This work provides a guide for thinking through key study design decisions.
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. 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.
5. 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.
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. Generating Real-World Evidence From AI Deployed in Health Systems.
主题：因果推断、RWE 与卫生经济学
相关性分数：4
期刊：Learning health systems
公开日期：2026-11-04（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: Health systems increasingly deploy predictive and generative artificial intelligence (AI) to improve care delivery and outcomes. Predictive AI models estimate the risk of future events to inform targeted interventions, while generative AI systems extract, summarize, and communicate information and may automate selected tasks. Routine deployment generates clinical, operational, and interaction data that can support evaluation of the effectiveness and safety of AI-enabled workflows.
METHODS: We review approaches to generating real-world evidence (RWE) from routine deployment of predictive and generative AI across four implementation configurations: silent deployment, human-in-the-loop (HITL), human-on-the-loop (HOTL), and automated. For each configuration, we describe the evaluation questions, routinely generated data, and feasible study designs.
RESULTS: Each implementation configuration supports different forms of evidence about model performance, workflow effectiveness, human oversight, and safety. For both predictive and generative AI, silent deployment supports assessment of local performance and subgroup differences. Once predictive AI drives action, evaluating the effectiveness of an implemented workflow (HITL, HOTL, or automated) generally requires causal inference approaches. For generative AI, HITL implementations can generate data on edits, overrides, time on task, usability, cognitive burden, and safety-relevant failure modes. HOTL and automated generative AI implementations can generate data on escalation performance, human follow-up work, downstream outcomes, and safety signals.
CONCLUSION: AI implementation should be paired with methods for generating RWE on the effectiveness and safety of AI-enabled workflows. In HOTL and automated configurations, escalation performance and residual human workload become particularly important components of evaluation.
9. Influence of Enrichment Criteria on eGFR Slope: Implications for Clinical Trial Design in CKD.
主题：临床试验方法与统计实践
相关性分数：4
期刊：Kidney international reports
公开日期：2026-09-17（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。
INTRODUCTION: Estimated glomerular filtration rate (eGFR) slope is increasingly employed as an intermediate endpoint in clinical trials, which are often enriched to select those at risk of more rapid eGFR decline. Herein, we explored the relative contribution of enrichment criteria to eGFR slope among patients with established chronic kidney disease (CKD).
METHODS: Using data from patients with at least 3 eGFR values from the Chronic Renal Insufficiency Cohort (CRIC) study (n = 4563), we used mixed effects regression to explore the association of baseline eGFR, 24-hour urine protein excretion (UPE), systolic blood pressure (SBP), and diabetes with annualized eGFR slope.
RESULTS: Mean baseline eGFR was 48 ± 16 ml/min per 1.73 m2, median UPE was 0.18 [25th, 75th percentile; 0.07, 0.70] g/d, mean SBP was 127 ± 20 mm Hg, and 49% had diabetes. Over a median follow-up of 7.1-year, eGFR changed by -1.30 (-1.36 to -1.24) ml/min per 1.73 m2 per year. In unadjusted models, higher UPE, SBP, and diabetes were associated with more rapid eGFR decline. Mean rates of decline with baseline eGFR < 45 and ≥ 45 ml/min per 1.73 m2 were -1.4 and -1.3 ml/min per 1.73 m2 per year, respectively (P = 0.42); UPE ≤ 0.3 g and > 0.3 g were -0.5 and -2.8 ml/min per 1.73 m2 per year, respectively; SBP < 130 and ≥ 130 mm Hg were -0.9 and -2.1 ml/min per 1.73 m2 per year, respectively; and for no diabetes and diabetes were -0.8 and -1.8, respectively (all P < 0.001).
CONCLUSION: Higher albuminuria appears to be the most potent predictor of more rapid eGFR decline. As higher (rather than lower) baseline eGFR predicts steeper subsequent eGFR decline, for patients with moderate to advanced CKD, a threshold-based decline in eGFR (e.g., 40, 50, or 57%) or a hierarchical composite endpoint might better capture treatment effects, rather than eGFR slope.
10. Targeting Accelerated Aging in COPD: The AMICO (A Trial of Metformin In COpd) Trial Design.
主题：临床试验方法与统计实践
相关性分数：4
期刊：COPD
公开日期：2026-11-04（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。
INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is increasingly recognized as a disease of accelerated biological aging characterized by progressive lung function decline, emphysema progression and multiple age-related comorbidities. Current therapies improve symptoms and reduce exacerbations but have limited effects on disease progression. Metformin has demonstrated anti-aging properties through modulation of pathways involved in oxidative stress, inflammation, mitochondrial dysfunction and cellular senescence, making it a potential disease-modifying treatment in COPD.
METHODS: AMICO (A Trial of Metformin In COPD) is an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled phase III trial conducted in anonymous. A total of 212 patients with clinically stable COPD, centrilobular emphysema on computed tomography, post-bronchodilator FEV1 40%-70% predicted and accelerated FEV1 decline (>40 mL·year-1) will be randomized (1:1) to receive metformin (850 mg twice daily) or matching placebo for 36 months in addition to standard COPD treatment. Assessments include pulmonary function, chest computed tomography, exercise capacity, health status, muscle strength, body composition, age associated comorbidities development and aging-related biomarkers.The primary endpoint is the annual rate of FEV1 decline over 36 months. Secondary endpoints include emphysema progression, changes in diffusing capacity, COPD Assessment Test score, 6-minute walk distance, BODE index, handgrip strength, exacerbations, major cardiovascular events, cancer incidence and renal dysfunction.
CONCLUSIONS: AMICO is the first randomized trial specifically designed to evaluate metformin as a gerotherapeutic and disease-modifying intervention in COPD. The study may provide novel evidence supporting geroscience-based approaches to slow disease progression and improve long-term outcomes in patients with COPD.
11. A randomised non-inferiority trial of CCTA guidance versus IVUS guidance for PCI: rationale and design of the P4 clinical trial.
主题：临床试验方法与统计实践
相关性分数：4
期刊：EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology
公开日期：2026-11-02（电子公开）
期刊卷期日期：2026-Nov-02
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。
Intravascular imaging-guided percutaneous coronary intervention (PCI) improves clinical outcomes compared with angiography-guided PCI. Contemporary coronary computed tomography angiography (CCTA) provides comprehensive assessment of coronary anatomy, plaque characteristics, vessel dimensions, calcification, and lesion-specific physiology, enabling detailed procedural planning before catheterisation. The Precise Procedural and PCI Plan (P4) trial is a prospective, international, multicentre, randomised, open-label trial with blinded endpoint adjudication designed to determine whether a comprehensive CCTA-guided PCI strategy is non-inferior to intravascular ultrasound (IVUS)-guided PCI with respect to clinical outcomes. Approximately 1,100 patients with chronic coronary syndromes or stabilised acute coronary syndrome, at least one coronary stenosis >70%, and fractional flow reserve derived from CCTA ≤0.80 are enrolled. Following central core laboratory confirmation of anatomical and physiological eligibility, patients are randomised 1:1 to CCTA-guided or IVUS-guided PCI. Patients assigned to CCTA-guided PCI undergo standardised procedural planning and virtual PCI simulation, with CCTA integrated into the catheterisation laboratory using computed tomography-fluoroscopy synchronisation for intraprocedural guidance. In the IVUS-guided arm, PCI is performed with mandatory pre- and post-PCI IVUS assessment. The primary endpoint is target vessel failure at 12 months, defined as the composite of cardiac death, target vessel myocardial infarction, or ischaemia-driven target vessel revascularisation. P4 will determine whether comprehensive, non-invasive CCTA-guided PCI planning is non-inferior to IVUS-guided PCI regarding 12-month target vessel failure while potentially improving procedural efficiency and standardisation. (ClinicalTrials.gov: NCT05253677).
12. Cost-effectiveness of recombinant influenza vaccine compared with standard-dose influenza vaccine among adults 50 years of age and older in Hong Kong.
主题：因果推断、RWE 与卫生经济学
相关性分数：4
期刊：Human vaccines & immunotherapeutics
公开日期：2026-11-02（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。
Older adults face a disproportionately high risk of severe influenza, yet the standard inactivated influenza vaccine (IIV) offers suboptimal protection in this population. This study evaluates the cost-effectiveness of replacing IIV with the recombinant influenza vaccine (RIV) for adults aged ≥50, ≥65, and ≥80 years in Hong Kong. We used a decision tree model to compare RIV with IIV for adults aged ≥50, ≥65, and ≥80 years in Hong Kong, from a societal perspective. Costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were evaluated, and the impact of parameter uncertainty on the results was assessed via deterministic and probabilistic sensitivity analyses. We found that for adults ≥ 50 years, RIV increased total costs by USD 5.1 (HKD 39.8) per person and gained 0.00012 QALYs (ICER: USD 40,659 [HKD 317,140] per QALY) compared with IIV. Among adults ≥65 years, RIV cost USD 6.0 (HKD 46.8) more and gained 0.00021 QALYs (ICER: USD 29,077 [HKD 226,801] per QALY). For adults ≥80 years, RIV cost USD 3.2 (HKD 25.0) more and gained 0.00015 QALYs (ICER: USD 21,092 [HKD 164,518] per QALY). ICERs were less than willingness-to-pay thresholds of one to three times Hong Kong’s gross domestic product per capita. In conclusion, RIV is cost-effective compared with IIV for adults ≥50, ≥65, and ≥80 years in Hong Kong, with the lowest ICER observed in individuals ≥80 years.
13. Established Versus Novel Strategies for Hepatitis B Functional Cure: A Cross-Regional Cost-Effectiveness Analysis of Pegylated Interferon and Bepirovirsen Add-on Therapy.
主题：因果推断、RWE 与卫生经济学
相关性分数：4
期刊：Journal of clinical and experimental hepatology
公开日期：2026-10-05（电子公开）
期刊卷期日期：2027
内容状态：待评估
为什么值得看：包含可供初筛的摘要；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/AIMS: Achieving functional cure (hepatitis B surface antigen [HBsAg] loss) and discontinuing lifelong nucleos(t)ide analog (NUCs) therapy are critical clinical goals in chronic hepatitis B (CHB) management. This study evaluated the long-term clinical outcomes and cost-effectiveness of different treatment strategies aimed at functional cure in hepatitis B e antigen (HBeAg)-negative patients with CHB across Asia-Pacific income strata.
METHODS: A Markov state-transition model was developed to project 30-yr hepatitis B virus (HBV) disease outcomes in HBeAg-negative patients. Three finite strategies, PegIFN add-on to NUCs (PegIFN+NUC), switching from NUCs to PegIFN (Switch), and bepirovirsen add-on to NUCs (Bepi+NUC), were compared with lifelong NUC therapy. Analyses were stratified by country income level (high-income country [HIC], upper-middle-income country [UMIC], and lower-middle-income country [LMIC]). Costs were estimated from the health care payer perspective in 2023 USD. Incremental cost-effectiveness ratios (ICERs), probabilistic sensitivity analyses, and cost-effectiveness acceptability curves were generated across a range of willingness-to-pay thresholds.
RESULTS: Switch led to the largest reduction in hepatocellular carcinoma (31%) and HBV-related deaths (32%). In HIC, Switch was the dominant strategy (lower cost and higher quality-adjusted life years [QALYs] than standard care). In UMIC and LMIC settings, Switch remained highly cost-effective with ICERs of 1774 and 2200 per QALY gained, respectively. Probabilistic sensitivity analysis demonstrated a >89% probability of finite PegIFN strategies being cost-effective at 1× GDP per capita thresholds across all income strata. In contrast, the bepirovirsen add-on strategy was dominated in all settings due to high acquisition costs and the impact of modeled seroreversion on long-term gains.
CONCLUSIONS: Finite PegIFN-based combination therapies are cost-effective toward functional cure in AP region. While bepirovirsen represents a major milestone in HBV drug development, its current economic viability is limited by high costs and durability concerns. Policy efforts should prioritize optimizing established immunomodulatory combinations to accelerate global hepatitis B elimination.
14. 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.
15. 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.
16. 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.
17. Wound-Only versus Weight-Based Rabies Immunoglobulin in Post-Exposure Prophylaxis: A Quasi-Randomized Asessor 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：The American journal of tropical medicine and hygiene
公开日期：2026-09-17（电子公开）
期刊卷期日期：2026-Nov-04
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。
Rabies is a fatal but preventable zoonotic disease that causes more than 20,000 deaths annually in India. Post-exposure prophylaxis (PEP) involves rabies vaccination and passive immunization with rabies immunoglobulin (RIG). Traditional RIG dosing is based on patient weight, whereas wound-only administration targets local viral neutralization at the exposure site. In the present study, antibody responses were compared after a three-dose anti-rabies vaccination in patients receiving either wound-only or weight-based RIG infiltration as part of PEP to assess the noninferiority of the wound-only approach. Patients with category III rabies exposure were enrolled in this noninferiority clinical trial, all of whom received a standard three-dose rabies vaccination. Rabies immunoglobulin was administered either according to body weight or infiltrated only around the wound. Serum rabies-neutralizing antibody titers were measured at predefined intervals. The primary outcome was the proportion of patients exhibiting protective antibody titers; secondary outcomes included RIG usage volume, adverse events, and feasibility in resource-limited settings. Both groups achieved adequate seroconversion with protective antibody titers. Wound-only RIG infiltration produced protective antibody responses comparable to weight-based RIG dosing while substantially reducing RIG volume used and could improve feasibility. Larger studies, including formal cost-effectiveness analyses, are needed to confirm the clinical and programmatic implications.
18. 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.
19. 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).
20. 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.