方法与临床研究雷达（2026-10-14）
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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. Group Sequential Sample Size for Comparing Two Survival Probabilities at a Specific Time Point.
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。
We propose a novel method that simultaneously determines the sample size for testing two survival probabilities at a pre-specified time while guaranteeing Type I error control in both fixed and group-sequential trial designs. Simulations across varying hypothesized differences, failure distributions, censoring proportions, and nominal powers demonstrate consistent performance, while interim analyses highlight maintained nominal Type I error control and increased power at each look relative to the standard binomial approach, regardless of the underlying failure time distribution or spending function. Importantly, our method is especially useful for evaluating survival outcomes at a fixed time in randomized trials where one treatment arm includes neoadjuvant therapy prior to surgery while the other involves surgery alone. Furthermore, it is advantageous when the proportional hazards assumption is not satisfied, as often occurs in immunotherapy trials with delayed or time-varying treatment effects or crossing survival curves. The method is also applicable to randomized Phase II trials, where smaller sample sizes and the use of intermediate or surrogate time-to-event endpoints demand efficient data use and robust error control. We illustrate the approach with motivating examples in renal and prostate cancer. An accompanying R Shiny application enables investigators to compute sample sizes interactively, facilitating practical trial planning in diverse settings.
5. 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.
6. 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.
7. 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.
8. Evaluating the Impact of Outcome Delay on the Efficiency of Sample Size Re-Estimation.
主题：临床试验方法与统计实践
相关性分数：5
期刊：Pharmaceutical statistics
公开日期：2026
内容状态：待评估
为什么值得看：包含可供初筛的摘要；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
Sample size re-estimation (SSR) can be a powerful tool to ensure that a clinical trial meets its pre-specified power requirements when uncertainty regarding a design parameter exists at the planning stage. However, long-term primary endpoints can be harmful to the efficiency of this trial design. If recruitment is continued while treatment outcomes are awaited, long delays can potentially lead to a large number of ‘pipeline’ participants being recruited in the trial that do not contribute to the interim analysis. This may lead to a larger number of recruited participants than are actually deemed required, resulting in an over-powered trial with high cost. This paper studies the exact impact of such outcome delay on the efficiency of ‘internal pilot’ type SSR designs. The distribution of the final sample size post SSR is obtained under various delay lengths for both continuous and binary outcome data; how delay impacts the precision of the final sample size estimate is then discussed. Precisely, the impact of delay on this precision is assessed through RMSE, as well as two more novel metrics, termed the delay impact and cost. The results indicate that with an increase in delay length, the delay impact increases, inflating average sample size and power. However, the severity of the effect of delayed outcomes depends highly on the exact trial setting. Trials where the re-estimated sample size is smaller than originally planned suffer the most from delayed outcomes, often leading to an over-powered trial. However, the impact of delay is substantially less if the originally planned sample size remains smaller than the re-estimated sample size.
9. Cost-effectiveness of finotonlimab plus bevacizumab versus sorafenib as first-line therapy in unresectable hepatocellular carcinoma in China.
主题：因果推断、RWE 与卫生经济学
相关性分数：5
期刊：Human vaccines & immunotherapeutics
公开日期：2026-07-27（电子公开）
期刊卷期日期：2026-Dec-31
内容状态：待评估
为什么值得看：包含可供初筛的摘要；已识别电子公开日期；通过方法学信号门槛；仍需阅读全文评价适用性与证据质量。
Hepatocellular carcinoma (HCC) imposes a substantial health burden in China. Finotonlimab plus bevacizumab recently prolonged progression-free survival (PFS) and overall survival (OS) vs. sorafenib, but its economic value remains unknown. Here we evaluated the cost-effectiveness of finotonlimab plus bevacizumab vs. sorafenib from the Chinese healthcare system perspective. Parametric survival models were fitted to extrapolate PFS and OS. Total costs, life-years (LYs), quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), incremental net monetary benefit (INMB), and incremental net health benefit (INHB) were estimated at a willingness-to-pay (WTP) threshold of $27,906 per QALY. Uncertainty was evaluated by one-way and two-way sensitivity analyses, probabilistic sensitivity analysis (PSA), subgroup analyses, scenario analyses, and price simulations. In the base-case analysis, sorafenib yielded 1.74 LYs and 1.25 QALYs at a total cost of $10,303.10, whereas finotonlimab plus bevacizumab yielded 3.01 LYs and 2.18 QALYs at a total cost of $58,595.49. Compared with sorafenib, the combination increased costs by $48,292.39 and generated gains of 1.27 LYs and 0.93 QALYs, resulting in ICERs of $38,203.46 per LY and $51,899.31 per QALY. INMB (-$22,325.82) and INHB (-0.80 QALYs) were negative. Sensitivity analyses identified PFS utility and bevacizumab cost as key drivers, but all ICERs remained above the WTP threshold. In PSA, the mean ICER was $50561.81 per QALY, and the probability of cost-effectiveness was 0% at the prespecified threshold. Based on the assumptions and inputs used in the present model, finotonlimab plus bevacizumab was unlikely to be cost-effective compared with sorafenib at the prespecified WTP in China.
10. 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. Weight-Loss Outcomes After Sleeve Gastrectomy Versus Tirzepatide in a Minority Cohort With Severe Obesity: Results From a Propensity Score Matched Cohort.
主题：因果推断、RWE 与卫生经济学
相关性分数：4
期刊：Clinical obesity
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。
While GLP-1 and GIP receptor agonists like semaglutide and tirzepatide have revolutionized pharmacologic obesity treatment, metabolic and bariatric surgery (MBS) continues to demonstrate superior weight loss and cost-effectiveness. Current evidence shows tirzepatide outperforms semaglutide with over 20% weight reduction, yet most clinical trials lack ethnic diversity, limiting the generalizability of these outcomes. This is a retrospective, single-centre study that evaluates 12-month weight loss results comparing tirzepatide and SG within a diverse, urban patient population. 12-month weight loss outcomes were compared between patients receiving tirzepatide and those undergoing sleeve gastrectomy (SG). Primary endpoints included changes in BMI, excess weight loss and total weight loss (TWL) percentage at 3, 6 and 12 months, following ASMBS reporting standards to evaluate treatment efficacy and comparative outcomes. Linear mixed models revealed statistically significant differences in weight loss between SG and tirzepatide cohorts across all time points (p < 0.001). By 12 months, the SG group was associated with greater weight loss than tirzepatide in this selected matched cohort with a 30% TWL and a 12 kg/m2 BMI reduction, compared to 12% TWL and 7 kg/m2 for tirzepatide. SG was associated with greater weight loss than tirzepatide in this selected matched cohort, especially for eligible patients in ethnic minority groups. However, tirzepatide serves as a vital non-invasive alternative, requiring individualized treatment decisions based on patient preference, cost and specific metabolic goals.
14. Optimizing pneumococcal prevention in South African older adults: Cost-effectiveness of PCV20 versus PPSV23 in the context of HIV-associated risk.
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：2026-10-08（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。
Pneumococcal disease remains a major cause of morbidity and mortality among older adults in South Africa, particularly among people living with HIV. Evidence on the cost-effectiveness of Prevnar 20 (PCV20) vs. Pneumovax 23 (PPSV23) vaccine in this setting remains limited. This study was conducted to evaluate the cost-effectiveness of PCV20 compared with PPSV23 vaccine among adults aged ≥65y in South Africa, and to assess the impact of HIV stratification on economic outcomes. A static decision-tree model was developed from the South African public healthcare payer perspective. The analysis incorporated invasive pneumococcal disease, pneumococcal community-acquired pneumonia, quality-adjusted life-years, maximum acceptable price, and 5y budget impact. HIV-stratified incidence and CD4-adjusted vaccine effectiveness were included. In the general population, PCV20 provided greater health benefits than PPSV23 but was not cost-effective at the current base-case price (USD 20.00/dose), with an ICER of USD 17,323/QALY. Price was the main driver of cost-effectiveness. In contrast, targeted vaccination of older adults living with HIV was economically favorable, with an ICER of USD 2,104/QALY under national incidence assumptions, and even stronger results in high-burden settings. The cost-effectiveness of PCV20 in South Africa is contingent upon the price of vaccine and risk-based targeting. Vaccinating all older adults universally may not be cost-effective at current prices, suggesting that targeted vaccination of older adults with HIV represents a more efficient strategy.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.