方法与临床研究雷达（2026-10-09）
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1. Social cognition as an under-used behavioural endpoint in neurodevelopmental psychopharmacology: A conditional framework for integrating theory of mind into clinical trial design.
主题：临床试验方法与统计实践
相关性分数：6
期刊：European journal of pharmacology
公开日期：2026-08-20（电子公开）
期刊卷期日期：2026-Oct-15
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
Social cognition, encompassing theory of mind (ToM), facial affect recognition, and mentalising under social load, is impaired across several neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), developmental language disorder (DLD), and intellectual disability (ID). These impairments are plausibly downstream of neurochemical processes, particularly serotonergic, dopaminergic, neuropeptidergic, and excitatory-inhibitory modulation of prefrontal-temporal-limbic circuits, although this pathway is indirect and moderated by age, language, cognitive ability, and comorbidity. Despite this, performance-based social cognition is rarely positioned as a primary or co-primary endpoint in NDD pharmacotherapy trials. The predominant standard, the Aberrant Behavior Checklist Irritability subscale and its caregiver-rated relatives, indexes reactive behavioural output that may be construct-distant from the mechanisms through which several contemporary agents are hypothesised to act. This narrative review advances a conditional thesis: endpoint-mechanism misalignment is one plausible contributor to the uninterpretability of certain null trials, alongside insufficient power, sample heterogeneity, unverified target engagement, dosing limitations, high placebo response, and genuine inefficacy. We synthesise condition-specific social-cognitive profiles with graded evidence, the neurobiological substrates across mechanism classes, and a three-tier framework positioning social cognition as a co-primary endpoint for mechanism-matched agents and as a prespecified secondary or moderator variable otherwise. We set out the measurement and regulatory preconditions fit-for-purpose validation, adequate test-retest reliability, practice-effect control, and defined meaningful change that must precede such repositioning. We do not claim ToM should replace existing endpoints or that it suits all NDD trials.
2. Application of competing risks models in cardiovascular mortality research: findings from the Tehran lipid and glucose study.
主题：生存与复杂事件结局方法
相关性分数：6
期刊：Journal of diabetes and metabolic disorders
公开日期：2026-07-21（电子公开）
期刊卷期日期：2026-Dec
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
PURPOSE: Cardiovascular diseases (CVD) are a leading cause of mortality in Iran and globally. This study aimed to provide more accurate estimates of associations between risk factors and CVD mortality by applying competing risk models within the Tehran Lipid and Glucose Study cohort.
METHODS: In this prospective analysis, 7,529 individuals aged ≥ 30 years without prevalent CVD were followed for a median of 19.87 years. The primary outcome was CVD mortality (n = 311), with non-CVD death as the competing event (n = 592). Analyses were stratified by sex and age (< 65 vs. ≥65 years). Cause-specific and Fine-Gray models estimated hazard ratios for diabetes, hypertension, hypercholesterolemia, smoking, and body mass index.
RESULTS: Diabetes and hypertension were the strongest predictors of CVD mortality across most subgroups. In the Fine-Gray model, diabetes showed the greatest impact in women < 65 years (HR: 4.83, p < 0.001), while hypertension showed the strongest association in women ≥ 65 years (HR: 3.32, p < 0.001). Hypercholesterolemia was associated with increased CVD mortality exclusively in women < 65 years (HR: 1.79, p = 0.02). Body mass index showed no significant association.
CONCLUSION: Diabetes and hypertension are the predominant risk factors for CVD mortality in the presence of competing risks, with effect magnitudes varying by sex and age. Applying competing risk models is essential for accurate risk estimation and targeted prevention in populations with high competing mortality burden.
3. Androgen receptor inhibitor double therapies in the management of metastatic castration-sensitive prostate cancer: a cost-effectiveness analysis.
主题：因果推断、RWE 与卫生经济学
相关性分数：5
期刊：Journal of medical economics
公开日期：2026-10-07（电子公开）
期刊卷期日期：2026-Dec
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
AIMS: To evaluate the cost-effectiveness of darolutamide plus androgen deprivation therapy (DARO+ADT) versus enzalutamide plus ADT (ENZA+ADT) and apalutamide plus ADT (APA+ADT) as first-line androgen receptor pathway inhibitor (ARPI) double therapies for metastatic castration-sensitive prostate cancer (mCSPC) from a US healthcare sector perspective.
METHODS: A partitioned survival model with three health states (progression-free mCSPC, progressed mCRPC, and death) projected lifetime costs and outcomes over a 30-year horizon with monthly cycles. DARO+ADT efficacy was derived from the ARANOTE trial; comparative efficacy for ENZA+ADT and APA+ADT was estimated via network meta-analysis-derived hazard ratios. Costs (drug acquisition, adverse event management, subsequent therapy, end-of-life care) and utilities were derived from trial data, published literature, and US cost sources. Costs and outcomes were discounted at 3% annually. Deterministic, probabilistic, and two-way sensitivity analyses assessed parameter uncertainty at a willingness-to-pay threshold of $150,000/QALY.
RESULTS: DARO+ADT generated 4.18 QALYs versus 4.03 (ENZA+ADT) and 3.99 (APA+ADT), driven by longer treatment persistence and lower adverse-event-related disutility. Versus ENZA+ADT, DARO+ADT yielded 0.15 incremental QALYs at $12,564 incremental cost (ICER: $85,108/QALY; net monetary benefit: $9,579). Versus APA+ADT, DARO+ADT was dominant (0.19 additional QALYs, $4,293 lower cost; net monetary benefit: $33,153). Two-way sensitivity analyses varying off-treatment utilities and post-discontinuation therapy costs showed that DARO+ADT remained cost-effective versus ENZA+ADT and dominant versus APA+ADT, respectively, across the parameter ranges tested. Probabilistic sensitivity analysis showed DARO+ADT was cost-effective in 51% and 52% of simulations versus ENZA+ADT and APA+ADT, respectively, which demonstrates uncertainty around the incremental findings.
LIMITATIONS: The analysis relies on indirect comparisons and extrapolated modeling, factors that may limit the generalizability of the findings.
CONCLUSIONS: DARO+ADT was cost-effective versus ENZA+ADT and dominant versus APA+ADT, driven by improved tolerability and treatment persistence, supporting its value as a first-line mCSPC option.
Prostate cancer is the most common cancer among men in the US and, when it spreads to other body parts but still responds to hormone-blocking treatment, it is called metastatic castration-sensitive prostate cancer (mCSPC). Newer drugs called androgen receptor pathway inhibitors (ARPIs), including darolutamide, enzalutamide, and apalutamide, are now commonly added to standard hormone therapy to improve outcomes, but no studies have directly compared these drugs against each other, and their costs and side-effect profiles differ. A partitioned survival model was built to estimate the long-term costs and health outcomes, from a US healthcare perspective, of treating mCSPC with darolutamide plus hormone therapy (DARO+ADT) versus enzalutamide plus hormone therapy (ENZA+ADT) or apalutamide plus hormone therapy (APA+ADT). The model used data from clinical trials and indirect treatment comparisons to project outcomes over patients’ lifetimes, accounting for how long patients stayed on treatment, side-effects, and costs of care after disease progression. The analysis found that DARO+ADT provided more quality-adjusted life years (QALYs) than either comparator, mainly because patients tended to stay on treatment longer and experienced fewer side-effects. Compared with ENZA+ADT, DARO+ADT provided a small additional health benefit at a modest additional cost, working out to a cost per QALY gained well within commonly accepted value thresholds. Compared with APA+ADT, DARO+ADT provided more health benefit while costing less overall, a favorable result in the base-case analysis. However, analyses accounting for uncertainty in the underlying data showed that the economic advantage of DARO+ADT was not decisive, with a roughly even chance that either drug could be the more cost-effective choice depending on the specific assumptions used. The findings suggest that darolutamide’s better tolerability and treatment persistence may make it a valuable first-line option for men with this type of advanced prostate cancer, potentially reducing complications and downstream healthcare costs while improving quality-of-life.
4. A Bayesian Adaptive Design for Assessing Treatment Effect Consistency in Bridging Studies.
主题：临床试验方法与统计实践
相关性分数：5
期刊：Statistics in medicine
公开日期：2026-Oct
内容状态：待评估
为什么值得看：包含可供初筛的摘要；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
Bridging studies serve as an efficient approach to evaluate the applicability of findings from an original study to a new population. We propose a Bayesian adaptive design for bridging studies with time-to-event endpoints, aiming to assess the consistency of treatment effects with those observed in the original study. The design adopts a group sequential framework, using posterior probabilities at interim and final analyses to evaluate the evidence for consistency between the bridging and original studies. If strong evidence of consistency or inconsistency is observed, the trial may be stopped early to conserve sample size. Additionally, a sample size recalculation strategy based on Bayesian predictive probability is incorporated to enhance flexibility. Simulation studies demonstrate that, compared to a commonly used method, the proposed design offers favorable operating characteristics. It maintains control of the empirical type I error rate through prespecified calibration, accounting for interim analyses (IAs) and sample size adaptation, and yields substantial sample size savings when the treatment effect in the bridging study is either highly consistent or clearly inconsistent with that of the original study.
5. A Practical Guide to Optimal Adaptive Two-Stage Designs for Various Endpoint Types.
主题：临床试验方法与统计实践
相关性分数：5
期刊：Pharmaceutical statistics
公开日期：2026
内容状态：待评估
为什么值得看：包含可供初筛的摘要；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
Adaptive designs are frequently used to adjust sample sizes based on interim data, ensuring reliable conclusions while protecting resources. To maximize trial efficiency, design parameters can be optimized to minimize an objective function (e.g., the expected sample size) while rigorously controlling overall error rates or further operating characteristics. However, existing methodological guidance for optimal adaptive designs mainly focuses on normally distributed data or discrete optimizations for binary data, leaving a limited practical framework to practitioners who work with other common endpoint types. We address this by demonstrating how the asymptotic normal approximations of standard test statistics enable the optimization framework to be systematically applied across diverse endpoint types, including binary and time-to-event data. Furthermore, we highlight critical pitfalls in using optimal adaptive designs for two-sided testing. The results demonstrate that optimizing design parameters can substantially decrease expected sample sizes and improve conditional power compared to standard group-sequential designs. Using this guidance, we aim to enable researchers to efficiently plan clinical trials in a broad spectrum of clinical settings, a factor that is especially crucial in rare disease research where only limited patient populations are available.
6. Evaluating the Impact of Outcome Delay on the Efficiency of Sample Size Re-Estimation.
主题：临床试验方法与统计实践
相关性分数：5
期刊：Pharmaceutical statistics
公开日期：2026
内容状态：待评估
为什么值得看：包含可供初筛的摘要；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
Sample size re-estimation (SSR) can be a powerful tool to ensure that a clinical trial meets its pre-specified power requirements when uncertainty regarding a design parameter exists at the planning stage. However, long-term primary endpoints can be harmful to the efficiency of this trial design. If recruitment is continued while treatment outcomes are awaited, long delays can potentially lead to a large number of ‘pipeline’ participants being recruited in the trial that do not contribute to the interim analysis. This may lead to a larger number of recruited participants than are actually deemed required, resulting in an over-powered trial with high cost. This paper studies the exact impact of such outcome delay on the efficiency of ‘internal pilot’ type SSR designs. The distribution of the final sample size post SSR is obtained under various delay lengths for both continuous and binary outcome data; how delay impacts the precision of the final sample size estimate is then discussed. Precisely, the impact of delay on this precision is assessed through RMSE, as well as two more novel metrics, termed the delay impact and cost. The results indicate that with an increase in delay length, the delay impact increases, inflating average sample size and power. However, the severity of the effect of delayed outcomes depends highly on the exact trial setting. Trials where the re-estimated sample size is smaller than originally planned suffer the most from delayed outcomes, often leading to an over-powered trial. However, the impact of delay is substantially less if the originally planned sample size remains smaller than the re-estimated sample size.
7. Cost-effectiveness of finotonlimab plus bevacizumab versus sorafenib as first-line therapy in unresectable hepatocellular carcinoma in China.
主题：因果推断、RWE 与卫生经济学
相关性分数：5
期刊：Human vaccines & immunotherapeutics
公开日期：2026-07-27（电子公开）
期刊卷期日期：2026-Dec-31
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
Hepatocellular carcinoma (HCC) imposes a substantial health burden in China. Finotonlimab plus bevacizumab recently prolonged progression-free survival (PFS) and overall survival (OS) vs. sorafenib, but its economic value remains unknown. Here we evaluated the cost-effectiveness of finotonlimab plus bevacizumab vs. sorafenib from the Chinese healthcare system perspective. Parametric survival models were fitted to extrapolate PFS and OS. Total costs, life-years (LYs), quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), incremental net monetary benefit (INMB), and incremental net health benefit (INHB) were estimated at a willingness-to-pay (WTP) threshold of $27,906 per QALY. Uncertainty was evaluated by one-way and two-way sensitivity analyses, probabilistic sensitivity analysis (PSA), subgroup analyses, scenario analyses, and price simulations. In the base-case analysis, sorafenib yielded 1.74 LYs and 1.25 QALYs at a total cost of $10,303.10, whereas finotonlimab plus bevacizumab yielded 3.01 LYs and 2.18 QALYs at a total cost of $58,595.49. Compared with sorafenib, the combination increased costs by $48,292.39 and generated gains of 1.27 LYs and 0.93 QALYs, resulting in ICERs of $38,203.46 per LY and $51,899.31 per QALY. INMB (-$22,325.82) and INHB (-0.80 QALYs) were negative. Sensitivity analyses identified PFS utility and bevacizumab cost as key drivers, but all ICERs remained above the WTP threshold. In PSA, the mean ICER was $50561.81 per QALY, and the probability of cost-effectiveness was 0% at the prespecified threshold. Based on the assumptions and inputs used in the present model, finotonlimab plus bevacizumab was unlikely to be cost-effective compared with sorafenib at the prespecified WTP in China.
8. 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.
9. DUBHE-H-308 study protocol: rationale and adaptive design of a randomized, open-label, seamless phaseII/III trial of iparomlimab and tuvonralimab (QL1706)-based regimens versus sintilimab plus bevacizumab as first-line treatment for advanced hepatocellular carcinoma.
主题：临床试验方法与统计实践
相关性分数：4
期刊：Future oncology (London, England)
公开日期：2026-10-01（电子公开）
期刊卷期日期：2026-Oct-01
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
No randomized trial has compared multiple immunotherapy-based combination strategies head-to-head in first-line advanced HCC, where approved doublet regimens achieve objective responses in fewer than one-third of patients. Iparomlimab and Tuvonralimab (QL1706), a new-type bifunctional combinedantibody (anti-PD-1/anti-CTLA-4 dual checkpoint inhibitor), deepens antitumor immunity while preserving tolerability. DUBHE-H-308 evaluates whether QL1706-based regimens, including a triplet with bevacizumab and oxaliplatin-based chemotherapy, can improve first-line outcomes in advanced HCC. DUBHE-H-308 (NCT05976568) is a prospective, randomized, open-label, multicenter, inferentially seamless phase II/III trial comparing three QL1706-based regimens against sintilimab plus bevacizumab in previously untreated advanced HCC. Three adaptive elements are incorporated: arm selection after phase II; seamless integration of phase II data into the phase III overall survival analysis; and a group-sequential interim analysis. Phase II co-primary endpoints are objective response rate and safety; the phase III primary endpoint is overall survival. Phase II enrollment is complete; interim data have guided regimen selection and confirmed transition to the confirmatory phase III stage. If successful, DUBHE-H-308 would provide the first randomized evidence supporting a triplet first-line strategy combining dual-checkpoint blockade, anti-VEGF therapy, and chemotherapy in advanced HCC, potentially establishing a new treatment standard. The adaptive framework maximizes efficiency without compromising confirmatory rigor.Clinical trial registration: ClinicalTrials.gov identifier NCT05976568.
Advanced liver cancer that cannot be removed by surgery is usually treated with drug combinations, but current two-drug regimens shrink tumors in fewer than one in three patients. QL1706 is a new “two-in-one” antibody that releases two of the brakes cancer uses to hide from the immune system. The DUBHE-H-308 study tests whether QL1706-based combinations especially a “triplet” adding bevacizumab, which cuts off the tumor’s blood supply, and platinum-based chemotherapy, improve outcomes for previously untreated patients, compared with the standard combination of sintilimab plus bevacizumab. Patients at multiple hospitals were randomly assigned to treatment groups. The trial uses an adaptive design: an early stage compared the combinations and selected the most promising one, and the study then moved into a larger confirmatory stage that measures how long patients live.Enrollment in the early stage is complete, and interim results confirmed the move into the final confirmatory stage. If positive, this would be the first randomized evidence that a three-drug strategy dual immune activation, anti-blood-vessel therapy, and chemotherapy works as a first-line treatment for advanced liver cancer, and could become a new standard of care.
10. WIse CHoices in the ICU (WICH-ICU): Protocol and Statistical Analysis Plan for a Stepped-Wedge Cluster Randomized Trial of Choosing Wisely Interventions in Swedish Intensive Care Units.
主题：临床试验方法与统计实践
相关性分数：4
期刊：Acta anaesthesiologica Scandinavica
公开日期：2026-Nov
内容状态：待评估
为什么值得看：包含可供初筛的摘要；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
BACKGROUND: Healthcare overuse, including unnecessary diagnostic testing and procedures, contributes to patient harm, increased healthcare costs, and resource waste. The Choosing Wisely initiative aims to reduce low-value care through evidence-based recommendations. However, limited evidence exists regarding the safety and effectiveness of implementing Choosing Wisely recommendations in intensive care settings.
METHODS: The WICH-ICU is a registry-based stepped-wedge cluster randomized controlled trial designed to evaluate the implementation of specific Choosing Wisely interventions in Swedish intensive care units (ICUs). The study will include adult patients treated in participating Swedish ICUs. The intervention consists of three parts of the Choosing Wisely recommendations: (1) reduced frequency of arterial blood gas sampling, (2) reduced routine laboratory testing, and (3) reduced routine chest radiography. The primary outcome is 30-day mortality. Secondary outcomes include ICU length of stay, duration of mechanical ventilation (invasive and noninvasive), continuous renal replacement therapy duration, and ICU readmission within 72 h. Intervention data, testing intensity (arterial blood gas samples, laboratory tests, and chest radiographs per patient-day), will be collected through local monitoring, while outcome data will be obtained from the Swedish Intensive Care Registry (SIR). The stepped-wedge design allows each participating ICU to serve as its own control, with randomized timing of intervention implementation.
DISCUSSION: This study will provide evidence on the safety and effectiveness of implementing Choosing Wisely recommendations in intensive care settings. The stepped-wedge cluster randomized design minimizes contamination while allowing all participating sites to eventually receive the intervention. The results will inform evidence-based de-implementation strategies in critical care.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT07013175.
11. Adaptive design strategies for ethical and efficient clinical trials using simulated annealing.
主题：临床试验方法与统计实践
相关性分数：4
期刊：Statistical methods in medical research
公开日期：2026-09-14（电子公开）
期刊卷期日期：2026-Oct
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
We introduce a flexible adaptive design strategy for treatment allocation in clinical trials based on a randomized simulated annealing algorithm. The proposed approach provides a unified and modular framework for implementing a broad range of adaptive randomization objectives, including covariate-adaptive (CA), response-adaptive (RA), covariate-adjusted response-adaptive (CARA), and hybrid RA+CA and CARA+CA designs. The procedure accommodates multiple treatments, different outcome types, and any baseline covariate information available. Its implementation is compatible with both parametric and nonparametric predictive models; in this work, we use Bayesian additive regression trees to capture complex covariate-response relationships without committing to a low-dimensional parametric specification. The allocation rule combines a simulated-annealing-based recommendation with a fallback randomization step used to ensure positive assignment probabilities. In a finite stratified setting, we establish strong consistency of the resulting stratified sample mean estimators. Extensive simulation studies with homogeneous and heterogeneous treatment effects show that our proposal achieves a favorable trade-off between ethical allocation and statistical efficiency. A redesign of the ACTG 175 clinical trial further illustrates the practical advantages and flexibility of the proposed framework.
12. Sample size calculation for the sequential multiple assignment randomized trial (SMART) design with a skewed outcome: Application to the SMART+ study.
主题：临床试验方法与统计实践
相关性分数：4
期刊：Statistical methods in medical research
公开日期：2026-09-12（电子公开）
期刊卷期日期：2026-Oct
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
With the rapid emergence of personalized healthcare, adaptive interventions have gained significant traction and relevance. Contemporary research has introduced a sophisticated trial design known as the sequential multiple assignment randomized trial (SMART) to advance the development of effective adaptive interventions. A critical element of the SMART design is the determination of the sample size. The existing literature provides sample size calculation formulas for SMART designs, which encompass a variety of approaches and types of outcome data. However, these formulas have primarily been developed under the assumption of normality for the outcome data. In practice, the fields where SMART is employed exhibit a significant prevalence of non-normality in the outcomes of interest. This paper delves into a specific scenario where the outcome demonstrates skewed behavior. We develop precision-based and power-based formulas for skewed outcomes, considering the requirements of both pilot and full-scale SMARTs. We present the operating characteristics of the formulas and perform extensive simulations under various design specifications to validate their usefulness. To demonstrate practical utility, we apply our formulas to the SMART+ study, a digital intervention trial that includes a skewed outcome among its outcomes of interest, highlighting relevance in real-world planning.
13. 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.
14. A multi-center, open-labelled, randomized controlled extended phase III non-inferiority clinical trial to evaluate the immunogenicity and tolerability of poliomyelitis vaccine (Vero cells), inactivated, Sabin strains administered with or without routine infant vaccines.
主题：临床试验方法与统计实践
相关性分数：4
期刊：Vaccine
公开日期：2026-08-27（电子公开）
期刊卷期日期：2026-Oct-03
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
BACKGROUND: Oral poliovirus vaccine (OPV) has been reported to cause vaccine-derived poliovirus and vaccine-associated paralytic poliomyelitis, and the limited global supply of conventional IPV has led many countries to rely on fractional-dose IPV regimens alongside OPV. The current study aims to assess the sIPV safety and immunogenicity when given concurrently with or in a staggered manner with routine immunization.
METHODS: A multi-country, multi-center, open-label, randomized controlled, extended phase III non-inferiority clinical trial was conducted with 1442 healthy infants aged 6-8 weeks from Bangladesh and Pakistan enrolled and randomized into four groups, i.e., co-administration group 1 (group C1), co-administration group 2 (group C2), staggered administration group 1 (group S1) and staggered administration group 2 (group S2). Antibody levels were determined using the collected sera for immunogenicity evaluation. The difference in seroconversion rates between the coadministration group and the staggered administration group is compared using the Cochran-Mantel-Haenszel χ2 (CMH-χ2) test, stratified by study site. Non-inferiority is concluded if the lower bound of the 95% confidence interval (CI) for the rate difference (coadministration group minus staggered administration group) is greater than -10%. The trial was registered prior to patient enrollment at clinicaltrials.gov (NCT05850364), and the protocol and statistical analysis plan are available at https://clinicaltrials.gov/study/NCT05850364. The trial is closed to new participants.
FINDINGS: The post-vaccination seroconversion rates for PV I were 90.3% (306/339) in group C1 and 87.0% (261/300) in group S1, for PV II, 91.7% (311/339) in group C1 and 91.3% (274/300) in group S1 and for PV III, 86.4% (293/339) in group C1 and 92.3% (277/300) in group S1. Among adverse reactions (ARs) reported within 7 days of vaccination, the incidence was similarly high in both the co-administration and staggered vaccination groups (92.8% vs. 95.5%).
INTERPRETATION: Our results demonstrated favorable safety and immunogenicity of co-administration of sIPV with other routine infant vaccines according to a 3-dose primary immunization schedule.
15. 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.
16. 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).
17. 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.
18. Perceived Utility of Combining Atypical Long-Acting Injectable Antipsychotics With Psychosocial Interventions: An Exploratory Survey of Mid-Career Psychiatrists in Japan.
主题：因果推断、RWE 与卫生经济学
相关性分数：3
期刊：Neuropsychopharmacology reports
公开日期：2026-Dec
内容状态：待评估
为什么值得看：包含可供初筛的摘要；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: Although combining long-acting injectable antipsychotics (LAIs) with psychosocial treatments for schizophrenia is important, psychiatrists’ attitudes toward this approach remain underexplored. We investigated Japanese psychiatrists’ perceptions of combining atypical LAIs with psychosocial interventions.
METHODS: An anonymous cross-sectional web-based survey was administered to 1038 mid-career Japanese psychiatrists, of whom 69 provided complete responses. Participants’ general attitude toward recommending atypical LAIs was dichotomized as positive or negative/neutral, and they rated on a 4-point scale the usefulness of combining atypical LAIs with five psychosocial interventions: (1) psychosocial treatment (e.g., psychoeducation), (2) day/night care, (3) community care, (4) financial/employment support, and (5) housing support.
RESULTS: Thirty-nine respondents held a positive attitude toward recommending atypical LAIs, whereas 30 held a negative/neutral attitude. A positive attitude was significantly associated with perceiving the combination as useful for psychosocial treatment (p = 0.038), financial/employment support (p = 0.015), and housing support (p = 0.041), but not for day/night care (p = 0.090) or community care (p = 0.079). Free-text rationales most commonly cited improved adherence and relapse prevention, enhanced illness insight, and synergistic effects as reasons for valuing the combination.
CONCLUSIONS: This exploratory study suggests that mid-career Japanese psychiatrists, particularly those with a favorable attitude toward atypical LAIs, perceive the combination of LAIs with psychosocial support not merely as an adherence tool but as a synergistic strategy promoting broader functional recovery. Because respondents represent a small, predominantly male, self-selected sample, the generalizability of the findings is limited.
19. Win Ratios in Ophthalmology-a Hierarchical Metric to Evaluate Adverse Outcomes in Comparative Studies.
主题：生存与复杂事件结局方法
相关性分数：3
期刊：Ophthalmology science
公开日期：2026-08-25（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。
PURPOSE: Clinical trials in ophthalmology frequently report multiple efficacy and safety outcomes of varying clinical importance analyzed either in isolation or as simple composites. The Win Ratio (WR) is a hierarchical composite metric originally developed to address such limitations in cardiovascular research by integrating outcomes according to their clinical priority. In this study, we assess its potential utility in ophthalmology outcomes with glaucoma surgery as the exemplar.
DESIGN: Retrospective registry-based study.
SUBJECTS: There are 1257 eyes that underwent a Xen gel stent (Xen) implantation or trabeculectomy (Trab) with a minimum 12 months of follow-up.
METHODS: Propensity score matching yielded two comparable cohorts (212 eyes each) without significant differences in age, baseline intraocular pressure, number of medications, visual acuity, or visual field mean deviation. A predefined hierarchy of eight adverse outcomes was constructed, headed by loss of light perception vision, secondary glaucoma surgery, followed by early postoperative complications (e.g., hypotony and hyphaema) or bleb needling. Each Xen-Trab pair was evaluated sequentially and classified as a win, loss, or tie.
MAIN OUTCOME MEASURES: The overall WR with 95% confidence intervals (CIs) and P value was estimated, and sensitivity analyses examined the robustness of results under alternative outcome hierarchies and random permutations.
RESULTS: The Xen group accumulated fewer wins than Trab (WR 0.83, 95% CI 0.63-1.10, P = 0.19), although the difference was not significant. Differences were driven by higher rates of secondary glaucoma surgery (18.4% vs. 12.7%) and bleb needling within the first 6 months (28.8% vs. 13.2%) in the Xen group, with remaining outcomes occurring infrequently and evenly distributed in each group. Sensitivity analyses with alternative hierarchies yielded consistent results (WR range 0.80-0.98), and random permutations of lower-ranked outcomes clustered around WR 0.77, supporting the consistency of the final outcome.
CONCLUSIONS: The WR offers a clinically meaningful, hierarchical approach to comparing multidimensional treatments that respects clinical priorities. Our findings illustrate the potential utility of this metric in the prospective evaluation of trial outcomes in ophthalmology.
FINANCIAL DISCLOSURES: The authors have no proprietary or commercial interest in any materials discussed in this article.
20. Blood kynurenine pathway metabolites show limited diagnostic utility for tuberculosis among adults living with human immunodeficiency virus and children in Uganda.
主题：因果推断、RWE 与卫生经济学
相关性分数：3
期刊：IJID regions
公开日期：2026-09-07（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。
OBJECTIVES: Traditional sputum-based diagnostics often demonstrate suboptimal diagnostic performance in people living with human immunodeficiency virus and children presenting with paucibacillary tuberculosis (TB). This study evaluated the diagnostic accuracy of circulating kynurenine-pathway metabolites against an authentic symptomatic control cohort in Uganda.
METHODS: Tryptophan, kynurenine, and the kynurenine-to-tryptophan ratio were quantified via ultra-performance liquid chromatography-tandem mass spectrometry in 70 adult people living with human immunodeficiency virus and 23 children presenting with presumptive TB.
RESULTS: Median biomarker concentrations demonstrated no statistically significant differences between participants with laboratory-confirmed TB and symptomatic controls. The kynurenine-to-tryptophan ratio yielded an area under the curve of 0.51 (95% confidence interval: 0.34-0.69) in adults and 0.62 (95% confidence interval: 0.36-0.87) in children, indicating limited diagnostic discrimination with substantial uncertainty, particularly in the small pediatric cohort. At the evaluated cutoff points, none of the biomarkers met the minimum sensitivity and specificity requirements defined by the World Health Organization target product profiles for diagnostic and screening tests.
CONCLUSION: Blood kynurenine pathway metabolites demonstrated limited clinical utility as standalone diagnostic biomarkers for active TB in these vulnerable populations. In addition, larger diagnostic performance studies are needed to address the uncertainty associated with the small sample size and to further validate our findings.