方法与临床研究雷达（2026-10-21）
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1. When Randomization Assigns a Starting Strategy: An Estimand-Led Framework for Frozen Embryo Transfer Trials.
主题：临床试验方法与统计实践
相关性分数：6
期刊：Therapeutic innovation & regulatory science
公开日期：2026-10-08（电子公开）
期刊卷期日期：2026-Oct-08
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。
Randomized trials may assign a treatment strategy rather than a fixed, uninterrupted exposure. Frozen embryo transfer (FET) provides a clear example: women can be randomized to start natural, modified natural, or artificial endometrial preparation, while cancellation and rescue artificial preparation change the care subsequently received. Unless the estimand is explicit, a terminal livebirth comparison can be mistaken for a comparison of uninterrupted protocols. Using the randomized trial by Ho et al. as a worked example, this Analysis examines how intercurrent events - particularly cancellation, delayed transfer, and rescue switching - shape the clinical question and interpretation. It distinguishes a starting-strategy estimand that uses a treatment-policy strategy for these events from completed-protocol and hypothetical no-switch estimands; it also develops patient-centered efficacy variables and denominator-aligned safety estimands. The framework recommends that FET trials prespecify the primary estimand, report cancellation and switching as core outcomes, include time and burden, align safety outcomes with biologically meaningful denominators, and document operational rules. Here, strategy denotes the intervention assigned at randomization, whereas pathway denotes the care sequence realized after assignment. This FET framework may serve as a prototype for other randomized trials of treatment algorithms, but generalization requires setting-specific estimand and intercurrent-event specification.
2. 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.
3. 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.
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. Enhancing learning health care systems with real-world data harmonization frameworks.
主题：因果推断、RWE 与卫生经济学
相关性分数：4
期刊：ESMO real world data and digital oncology
公开日期：2026-10-12（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。
The use of digital tools has enabled the capture of clinical data that can be leveraged to produce real-world evidence, complementing traditional trial data and addressing evidence gaps in oncology. Electronic health records offer rich, longitudinal data, although recording practices, collection methods, and quality may vary over time and across settings, which can lead to inconsistencies. Data harmonization is key to overcoming fragmentation, and common data models offer structured methods for unifying diverse health care data. Various mapping strategies standardize data balancing, automation, flexibility, and semantic precision: ‘upstream semantic mapping’ emphasizes standardization, ‘downstream semantic mapping’ allows tailored adjustments by local experts, and ‘direct dataset mapping’ focuses on creating analysis-ready datasets without intermediate data transformation. The best approach depends on organizational needs, data characteristics, and intended use cases, but harmonization must be a continuous process that adapts to evolving data sources, variable data types, new collection methods, and shifting transformation practices. Clinical expertise must ensure that cohorts mirror real-world scenarios and capture local nuances, more often with an artificial intelligence-assisted framework, while epidemiologists must consider harmonization practices in the study design and analysis. Data strategies must protect patient privacy while supporting health care improvements, with secure data handling paired with accessible sharing. By engaging medical professionals at every stage, health care institutions can become learning health systems driven by high-quality observational research, ultimately advancing knowledge and improving patient outcomes.
9. Adaptation of Bayesian decision analysis for clinical trial design to binary outcomes: illustration for Ebola virus disease treatment.
主题：临床试验方法与统计实践
相关性分数：4
期刊：Journal of biopharmaceutical statistics
公开日期：2026-10-15（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。
When designing trials for high-mortality diseases with limited therapies, the conventional 5% type I error rate (α) may be unsuitable. A higher α could benefit seriously ill patients lacking therapeutic alternatives. Bayesian decision analysis (BDA) integrates multiple health consequences into trial design. We extend BDA for trials with binary outcomes to calculate optimal sample sizes (n) and α in an Ebola outbreak context. We consider fixed, two-arm randomized trials with binary outcomes and two types of clinical trial losses: post-trial loss, for not approving an effective treatment or approving an ineffective one; in-trial loss, for not administrating an effective treatment to control-arm patients or for administrating an ineffective treatment to experimental-arm patients. The model incorporates treatment side effects and disease severity into a single loss function, from which BDA-optimal n and α are derived. Using mortality as the outcome, we modeled various epidemic scenarios by varying target population size, mortality rate, and treatment efficacy. In most cases, BDA-optimal α exceeded the conventional one-sided 2.5% and sample sizes are smaller. Simulations comparing BDA-optimized two-arm trials (fixed/sequential) to conventional designs (two-arm/single-arm, fixed/sequential) across outbreak scenarios show comparable statistical power across designs, except when sample size assumptions are incorrect, or when trials started after the outbreak peak; in these situations, BDA-optimized trials show superior powers. This BDA framework provides a promising approach for designing trials with binary outcomes, particularly in high-mortality disease outbreaks, where declining case numbers and uncertain mortality and efficacy data challenge conventional methods.
10. Worsening heart failure is not a single endpoint: a severity-gradient perspective from digoxin in rheumatic heart disease.
主题：临床试验方法与统计实践
相关性分数：4
期刊：Heart failure reviews
公开日期：2026-10-10（电子公开）
期刊卷期日期：2026-Oct-10
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 composite of cardiovascular or all-cause death and worsening heart failure (WHF) has become the principal efficacy endpoint of heart failure trials. Yet WHF is not one event: it spans outpatient oral-diuretic escalation, urgent intravenous-diuretic visits, hospitalisation, and HF-related death-tiers that differ markedly in frequency, ascertainment, and prognostic weight. A composite WHF benefit therefore cannot be properly interpreted without knowing which tier carries the signal, and we argue that this tier is both phenotype- and setting-dependent. Two trials published on the same day in 2026 make the point with unusual clarity. In the Dig-RHD trial of digoxin in rheumatic heart disease, the benefit concentrated in outpatient diuretic events, with neutral results at hospitalisation and death; in a contemporaneous meta-analysis of digitalis glycosides in reduced or mildly reduced ejection fraction, the same drug class reduced worsening heart failure mainly through hospitalisation, again without a mortality benefit. We use this contrast to propose a severity-gradient framework for reporting and interpreting worsening heart failure, and discuss its implications for trial design, for the translation of guideline-based evidence across health systems, and for the use of inexpensive therapies such as digoxin in low- and middle-income settings.
11. 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.
12. Attrition adjustment in sample size calculation for Intention-to-treat (ITT)-based clinical trials: Evidence from a clinical trial simulation study.
主题：临床试验方法与统计实践
相关性分数：4
期刊：British journal of clinical pharmacology
公开日期：2026-10-09（电子公开）
期刊卷期日期：2026-Oct-09
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
AIMS: Attrition in randomized clinical trials (RCTs) threatens internal validity and reduces statistical power, challenging the integrity of analyses. Different methods to handle missing data such as last observation carried forward (LOCF), multiple imputation (MI) and per-protocol (PP) vary in bias and impact. Whether to inflate sample size to offset dropout remains debated, necessitating systematic investigation to evaluate effects of missing data strategies and sample size adjustments on trial outcomes.
METHODS: A Monte Carlo simulation modelled parallel-arm RCTs with correlated baseline and longitudinal continuous outcomes. Four missingness mechanisms, that is, missing completely at random (MCAR), missing at random (MAR), missing not at random (MNAR) and differential dropout, were studied with dropout rates up to 20%. Analytical approaches included PP, LOCF and MI. Scenarios were replicated 1000 times. Key metrics were power, bias, Type I error and sensitivity assessed by tipping point and scenario analyses.
RESULTS: At 20% dropout, MI preserved power at approximately 72%-73% under MCAR, MAR and MNAR mechanisms, surpassing PP (~68%-70%) and LOCF (~59%-61%). Attrition-adjusted sample size restored power to approximately 79%-82% across mechanisms. Differential dropout produced the greatest bias and power reduction for all methods and was the only mechanism showing meaningful Type I error inflation. Tipping-point analyses confirmed that conclusions remain robust to deviations from the MAR assumption.
CONCLUSIONS: Combining prospective sample size inflation with MI enhances internal validity and power in RCTs facing attrition. These findings have important implications for clinical trial guidelines, especially in sample size estimation and missing data handling, promoting evidence-based standards to maintain trial integrity.
13. Perspectives on the Use of a Bayesian Approach in Designing Seamless Phase 2/3 Clinical Trials with Dose Selection, Early Stopping for Futility and Efficacy, or Sample Size Re-estimation.
主题：临床试验方法与统计实践
相关性分数：4
期刊：Therapeutic innovation & regulatory science
公开日期：2026-10-07（电子公开）
期刊卷期日期：2026-Oct-07
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。
Seamless Phase 2/3 clinical trial designs have become an increasingly attractive strategy to improve development efficiency by reducing the time between development phases and enabling the reuse of early-stage data in confirmatory analyses. In parallel, Bayesian methods have gained attention for their ability to support adaptive decision-making under uncertainty, particularly in complex trial designs. In this article, we discuss perspectives on the use of Bayesian approach in designing inferentially seamless Phase 2/3 trials that incorporate dose selection, early stopping for futility or efficacy, and sample size re-estimation. We outline key advantages and limitations of seamless approaches compared with separate Phase 2 and Phase 3 trials, and we contrast Bayesian and frequentist frameworks, including hybrid designs that combine Bayesian interim decision rules with frequentist final inference. Particular emphasis is placed on operating characteristics that are informative for trial planning and regulatory discussions, such as predictive probabilities of success, probabilities of false and correct conclusions, dose selection probabilities, and expected sample size. We propose an iterative design process that integrates prior internal and external evidence, multidisciplinary stakeholder input, and extensive simulation to calibrate decision rules. A detailed case study of an inferentially seamless Phase 2/3 trial illustrates how Bayesian posterior and predictive probabilities can guide interim decisions on dose selection, futility stopping, and adaptive sample size modification, while maintaining strong control of the family-wise error rate at the final analysis. We conclude that the use of Bayesian methods in designing seamless Phase 2/3 designs, when carefully planned and transparently evaluated through simulations, can provide a flexible and efficient framework for accelerating drug development while supporting robust and interpretable decision-making.
14. 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.
15. Cost-effectiveness of an online personalised parenting intervention to prevent affective disorders in high-risk adolescents compared to a standard educational package.
主题：因果推断、RWE 与卫生经济学
相关性分数：4
期刊：Journal of affective disorders
公开日期：2026-09-07（电子公开）
期刊卷期日期：2026-Dec-15
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
BACKGROUND: Adolescent depression is associated with substantial health and economic burden. Preventive interventions that strengthen parenting skills show promise in reducing depressive symptoms and improving adolescent well-being. However, evidence on the cost-effectiveness of scalable online parenting interventions remains limited.
OBJECTIVES: To evaluate the cost-effectiveness of an online personalised parenting (PP) programme - Partners in Parenting - designed to prevent affective disorders in high-risk adolescents, compared with a standard educational package.
METHODS: This trial-based economic evaluation was conducted alongside a randomised controlled trial of 512 parent-adolescent dyads (256 per arm). Analyses adopted UK public sector and societal perspectives over 15 months. Costs (2022-2023 GBP) were collected prospectively. Utilities from EQ-5D-Y and CHU9D were used to estimate quality-adjusted life-years (QALYs). The base case used bivariate regression of costs and QALYs with multiple imputations under intention-to-treat. Incremental cost-effectiveness ratios, net monetary benefits, and cost-effectiveness acceptability curves were estimated. Sensitivity analyses assessed robustness.
RESULTS: In the adjusted multiply imputed base-case analysis, mean incremental public-sector costs were £639 (95% CI £272 to £988) and mean incremental QALYs were 0.013 (95% CI -0.021 to 0.042), corresponding to a 13%-27% probability of cost-effectiveness at willingness-to-pay thresholds of £20,000-£30,000 per QALY. Complete-case analysis suggested lower costs and higher QALYs but with substantial uncertainty.
CONCLUSIONS: Over the 15-month trial horizon, the personalised parenting programme was associated with higher costs, a small and uncertain gain in QALYs, negative incremental net monetary benefit, and a low probability of being cost-effective at NICE-recommended willingness-to-pay thresholds.
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. Clinical Trial Design Considerations for the Development of Disease-Modifying Therapies for Type 1 Diabetes.
主题：临床试验方法与统计实践
相关性分数：3
期刊：Diabetes
公开日期：2026-10-20（电子公开）
期刊卷期日期：2026-Oct-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。
Several disease-modifying therapies have reduced the progressive loss of β-cell function in type 1 diabetes, with efficacy observed across a wide array of underlying therapeutic mechanisms of action. These successes highlight opportunities to accelerate the development of novel and repurposed type 1 diabetes treatments; however, only one such therapy has received regulatory approval for clinical use and few phase 3 clinical trials have been performed. For bringing emerging therapies to people living with type 1 diabetes as quickly and efficiently as possible, overall regulatory strategy and clinical trial design, especially inclusion criteria and end point selection, are essential, and planning must include their careful consideration. The considerations discussed herein represent a feasible and promising road map for developers of disease-modifying therapies and establish that type 1 diabetes remains a promising area for continued investment.