Judy Zhong

Clinical Trial Centers (CTCs) manage complex multi-site trials under rising regulatory and operational demands. Traditional workflows are labor-intensive and error-prone. Existing AI handles narrow and siloed tasks. We introduce Agent System for TRial Automation (ASTRA), a proposed multi-agent CTC in which a central Coordinator Agent and site-level Agents orchestrate domain-specialized AI-agent teams under human supervision. In this framework, agents follow standard messaging using shared environments and a version-controlled knowledge base. This manuscript introduces ASTRA as a design framework and summarizes key implementation and regulatory challenges for this hybrid automation-plus-oversight model.

Purpose: Vesicourethral anastomotic stenosis (VUAS) occurs after 1 to 3% of robotic-assisted radical prostatectomies (RARPs). Pelvic fascia–sparing techniques preserve more native anatomy and may reduce stenoses, but evidence is lacking. The aim of this study was to compare stenosis incidence, management, and outcomes after standard vs pelvic fascia–sparing RARP. Materials and Methods: We conducted a multi-institutional retrospective study of 910 standard, 409 Retzius-sparing, and 272 hood RARP during February 2012-September 2025. Standard and hood techniques used 18Fr urethral catheters, and the Retzius-sparing technique used 18Fr suprapubic catheters. The primary end point was cystoscopically confirmed VUAS requiring intervention within 12 months. Urinary continence was assessed using the validated Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP). Multivariable logistic regression assessed factors associated with VUAS. Results: There were 19 VUASs overall, with an incidence of 1.6%, 1.5%, and 0% after standard, hood, and Retzius-sparing techniques, respectively. In 88.2%, VUAS resolved with a single endoscopic incision or dilation followed by 6 months of intermittent self-catheterization, without worsening urinary continence ( P = .317). In adjusted analyses, Retzius-sparing vs standard RARP was associated with lower odds of VUAS (odds ratio [OR] 0.051; 95% confidence interval [CI] 0.003 to 0.870; P = .040). Diabetes was associated with almost three-fold higher odds of VUAS (OR 2.974; 95% CI 1.146-7.721; P = .025). Increasing surgeon experience was associated with fewer VUASs (OR 0.998; 95% CI 0.995-1.000; P = .046). Conclusions: There were no VUAS after Retzius-sparing RARP, and Retzius-sparing vs standard approach was associated with lower odds of stenosis. Endoscopic management with structured self-catheterization achieved high success without worsening incontinence. Prospective studies are needed to validate our findings.

Aims: Treatment discontinuation is a common intercurrent event in randomized clinical trials (RCTs) that can bias treatment effect estimates, yet it remains under recognized and inconsistently addressed. Antithrombotic trials provide a relevant case, as bleeding-related discontinuation is common and more often occur in patients at increased risk also for ischaemic events. Methods and results: We reviewed large antithrombotic RCTs published in The New England Journal of Medicine (2020–2025) to assess reporting and analytic handling of treatment discontinuation. We also conducted simulations to examine how discontinuation patterns influence efficacy estimates under three scenarios: discontinuation only in the treatment arm, in both arms with similar patterns, and in both arms but outcome-associated only in the treatment arm. Treatment policy (intention-to-treat) and while-on-treatment strategies were compared within the ICH E9(R1) framework. Among fourteen reviewed antithrombotic RCTs, about one-third of patients discontinued treatment in trials with more than 6 months follow-up, with higher imbalance in open-label studies. Over half of discontinuations were safety-related, yet timing and temporary interruptions were rarely reported. Most reported both ITT and per-protocol (PP) analyses, with PP assuming non-informative censoring and yielding larger efficacy estimates. In simulations, treatment policy and while-on-treatment strategies were biased when discontinuation was outcome-associated, while Simon–Makuch curves helped identify prognostic discontinuation differing by treatment arm. Conclusion: Discontinuation is common, prognostically meaningful, and often oversimplified in analysis, threatening the validity of RCT findings. Explicitly addressing discontinuation as an intercurrent event within the estimand framework, along with stratified outcome curves, can improve interpretation and support more robust trial conclusions.

Emerging evidence suggests that concurrent COVID-19 mRNA vaccination may enhance immune checkpoint inhibitors (ICIs) effectiveness by augmenting antitumor immune activation. Yet real-world estimates of survival benefit across cancers and clinical subgroups are limited. We emulated a randomized trial comparing two strategies at initiation of first-line ICI therapy: receipt of ≥1 COVID-19 mRNA vaccine within 100 days of ICI initiation versus no vaccination. Using the TriNetX linked network, we identified 7,966 adults with lung, melanoma, or kidney cancers who initiated first-line ICI between Sep 2020 and Nov 2024, among whom 458 received a COVID-19 vaccine within ±100 days of initiation. Vaccination was associated with improved overall survival (OS) and treatment-free survival (TFS) in lung cancer (OS aHR, 0.81; 95% CI, 0.74–0.89; P<0.001), with a modestly longer 3-year mean OS of 2.33 months (95% CI, 1.41–3.23; P<0.001). Vaccination was not associated with TFS or OS improvement in kidney or melanoma.

Background and Objective: A posterior approach to endopelvic neurovascular total sparing (PATENTS) during robotic-assisted radical prostatectomy (RARP) may improve recovery of sexual function through preservation of anterolateral periprostatic tissue. We compared RARP erectile function recovery with PATENTS vs the conventional anterior nerve-sparing approach. Methods: We conducted a single surgeon retrospective review of 495 RARP (278 anterior nerve-sparing, 217 PATENTS) performed during 2015 to 2025, with initiation of PATENTS in 2022. Our primary outcome was erectile function recovery defined as erections sufficient for sexual activity (at least masturbation/foreplay) from the Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP). Cox proportional hazard models evaluated factors affecting recovery of erectile function. Key Findings and Limitations: PATENTS patients were older (median 66 vs 64 years; P = .002) and more likely to have clinically significant cancer at diagnosis (95.8% vs 86.0%; P = .003). Despite shorter follow-up (5 months [IQR 3-15] vs 10 [3-21], P < .001), PATENTS was associated with shorter duration to erections sufficient for intercourse ( P = .022). In adjusted analyses, PATENTS was associated with improved erections firm enough for intercourse (hazard ratio [HR] 2.3, confidence interval [CI]: 1.45-3.68, P < .001), erections firm enough for sexual activity (HR 1.5, CI: 1.21-1.96, P < .001), and any partial erections (HR 1.4, CI: 1.13-1.63, P < .001). There were no differences in margin status ( P = .234) or adverse events ( P = .933). Study limitations include single surgeon, retrospective study design. Conclusions and Clinical Implications: PATENTS facilitated recovery of erectile function without compromising surgical margins or adverse events. Prospective, multisurgeon series are needed to validate our findings.

Objectives: This study aimed to describe the implementation of a workplace health promotion to address low levels of physical activity (PA). Methods: Using the Exploration, Preparation, Implementation, Sustainment (EPIS) framework, we implemented and evaluated a 10-week workplace step-count challenge to promote PA. All health system employees invited to participate. Data were collected on the exploration, preparation, and implementation phases. Results: During exploration, we recognized inadequate PA among employees. Meetings with key personnel were held to determine details of the health promotion and obtain support. We pursued a step-count PA intervention, capitalizing on employee ownership of smartphones with accelerometers. Vendors to host the intervention were evaluated. All employees were invited to participate. Participants received weekly messages about improving PA and notifications of weekly challenges. Exit interviews provided feedback and suggestions. Conclusions: A workplace health promotion focused on employee PA is feasible using EPIS.

We introduce a widely applicable model-based approach for estimating individual-level Social Determinants of Health (SDoH) and evaluate its effectiveness using the All of Us Research Program. Our approach utilizes aggregated SDoH datasets to estimate individual-level SDoH, demonstrated with examples of no high school diploma (NOHSDP) and no health insurance (UNINSUR) variables. Models are estimated using American Community Survey data and applied to derive individual-level estimates for All of Us participants. We assess concordance between model-based SDoH estimates and self-reported SDoHs in All of Us and examine associations with undiagnosed hypertension and diabetes. Compared to self-reported SDoHs, the area under the curve for NOHSDP is 0.727 (95% CI, 0.724-0.730) and for UNINSUR is 0.730 (95% CI, 0.727-0.733) among the 329 074 All of Us participants, both significantly higher than aggregated SDoHs. The association between model-based NOHSDP and undiagnosed hypertension is concordant with those estimated using self-reported NOHSDP, with a correlation coefficient of 0.649. Similarly, the association between model-based NOHSDP and undiagnosed diabetes is concordant with those estimated using self-reported NOHSDP, with a correlation coefficient of 0.900. The model-based SDoH estimation method offers a scalable and easily standardized approach for estimating individual-level SDoHs. Using the All of Us dataset, we demonstrate reasonable concordance between model-based SDoH estimates and self-reported SDoHs, along with consistent associations with health outcomes. Our findings also underscore the critical role of geographic contexts in SDoH estimation and in evaluating the association between SDoHs and health outcomes.

Electronic health records (EHRs) contain rich clinical information for millions of patients and are increasingly used for public health research. However, non-random inclusion of subjects in EHRs can result in selection bias, with factors such as demographics, socioeconomic status, healthcare referral patterns, and underlying health status playing a role. While this issue has been well documented, little work has been done to develop or apply bias-correction methods, often due to the fact that most of these factors are unavailable in EHRs. To address this gap, we propose a series of Heckman type bias correction methods by incorporating social determinants of health selection covariates to model the EHR non-random sampling probability. Through simulations under various settings, we demonstrate the effectiveness of our proposed method in correcting biases in both the association coefficient and the outcome mean. Our method augments the utility of EHRs for public health inferences, as we show by estimating the prevalence of cardiovascular disease and its correlation with risk factors in the New York City network of EHRs.

Background: We previously reported a higher incidence of a pathogenic germline variant in the kinase insert domain receptor (KDR) in melanoma patients compared to the general population. Here, we dissect the impact of this genotype on melanoma tumor growth kinetics, tumor phenotype, and response to treatment with immune checkpoint inhibitors (ICIs) or targeted therapy. Methods: The KDR genotype was determined and the associations between the KDR Q472H variant (KDR-Var), angiogenesis, tumor immunophenotype, and response to MAPK inhibition or ICI treatment were examined. Melanoma B16 cell lines were transfected with KDR-Var or KDR wild type (KDR-WT), and the differences in tumor kinetics were evaluated. We also examined the impact of KDR-Var on the response of melanoma cells to a combination of VEGFR inhibition with MAPKi. Results: We identified the KDR-Var genotype in 81/489 (37%) patients, and it was associated with a more angiogenic (p = 0.003) and immune-suppressive tumor phenotype. KDR-Var was also associated with decreased PFS to MAPKi (p = 0.022) and a trend with worse PFS to anti-PD1 therapy (p = 0.06). KDR-Var B16 murine models had increased average tumor volume (p = 0.0027) and decreased CD45 tumor-infiltrating lymphocytes (p = 0.0282). The anti-VEGFR treatment Lenvatinib reduced the tumor size of KDR-Var murine tumors (p = 0.0159), and KDR-Var cells showed synergistic cytotoxicity to the combination of dabrafenib and lenvatinib. Conclusions: Our data demonstrate a role of germline KDR-Var in modulating melanoma behavior, including response to treatment. Our data also suggest that anti-angiogenic therapy might be beneficial in patients harboring this genotype, which needs to be tested in clinical trials.