Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
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Journal of the American Medical Informatics Association : JAMIA
Sociodemographic bias in large language model clinical trial screening
OBJECTIVE: To assess whether large language model (LLM)-based clinical trial screening judgments vary by patient sociodemographic characteristics. MATERIALS AND METHODS: We conducted a cross-sectional evaluation of Phase II-III US adult randomized controlled trial (RCT) protocols (2023-2024). Physician-validated clinical vignettes were evaluated in a control version and 33 sociodemographic identity variants differing only by labels. Nine LLMs assessed eligibility and related domains. Mixed-effects models estimated adjusted differences vs control. RESULTS: Across 58 protocols and 5.3 million evaluations, eligibility judgments were largely stable across identities. Race and ethnicity showed minimal effects after accounting for socioeconomic status. Homelessness produced the largest negative eligibility shift and pronounced effects in adherence, resources, and trust. DISCUSSION AND CONCLUSION: LLMs applied explicit eligibility criteria consistently, but disparities emerged in domains requiring inference about behavior or resources, underscoring the need for careful deployment to promote fair trial access.
2 Aug 2026
Read appraisal →Gut
Digital twins in IBD-bridging data, biology and trial innovation
Clinical trials in IBD face difficulties of escalating complexity, high costs and challenges in recruitment. Digital twins are virtual, data-driven replicas of individual patients that model disease trajectories and treatment responses, which offer a potential innovative change in the conduct of clinical trials in IBD. Built from multimodal datasets integrating clinical, molecular, imaging and real-world data, digital twins can generate synthetic control arms, enable adaptive randomisation and predict disease relapse or treatment response. Early studies across oncology, cardiology and endocrinology demonstrate their feasibility and potential to improve statistical power while reducing patient burden. However, the integration of digital twins into clinical trials in IBD will require rigorous validation frameworks, transparent data governance and attention to algorithmic bias and consent. In this review, we explore how digital twins may transform IBD research-from in silico simulation to adaptive, patient-centred trial design-and outline the regulatory, ethical and logistical challenges to be considered in order to successfully integrate them into future trials.
10 July 2026
Read appraisal →Infectious diseases of poverty
Broadly neutralizing antibodies for HIV therapy in clinical trials: a systematic review
BACKGROUND: Lifelong daily antiretroviral therapy (ART) effectively suppresses human immunodeficiency virus type 1 (HIV-1) replication but does not eradicate the virus, underscoring the urgent need for long-acting antivirals and functional cure strategies. Broadly neutralizing antibodies (bNAbs) have emerged as a promising approach for achieving durable HIV-1 remission. In this systematic review, we summarize recent advances in the development of bNAbs for HIV-1 treatment. METHODS: We searched PubMed, Embase, and Web of Science for clinical trials published up to March 22, 2026. We included data evaluating intravenously administered bNAbs, with or without concomitant conventional ART, and comparing them with placebo, ART or no intervention. These data were used to evaluate the pharmacokinetics, antiviral efficacy, resistance profiles, immunologic effects, and safety of intravenously administered bNAbs. RESULTS: LS-modified bNAbs extended half-life by 2- to 5-fold relative to their parental counterparts (e.g., VRC01LS: 71 vs 15 days), although viremia reduced half-life by 20-40%. In viremic participants harboring bNAb-sensitive virus, monotherapy achieved viral load (VL) reductions of 0.93-1.8 log₁₀ copies/ml, with rebound occurring within approximately 4-8 weeks, whereas combinations regimens achieved declines of up to 2.04 log₁₀ copies/ml and delayed rebound to 15-33 weeks. No consistent reduction in total reservoir size was observed, although early intervention and baseline viral sensitivity appeared to limit reservoir expansion. Resistance emerged through epitope-proximal mutations, with cross-resistance observed mainly among antibodies targeting shared epitope classes. Overall, bNAbs were well tolerated, with rare discontinuations (0.4%) and low immunogenicity. CONCLUSIONS: LS-engineered bNAbs exhibit a longer half-life than their parental antibodies. Combination regimens achieve greater VL reductions and a longer delayed rebound compared with monotherapy, indicating that LS-modified multi-epitope bNAb cocktails are promising for long-acting HIV-1 remission. To become clinically competitive, larger resistance-guided trials are needed to extend dosing intervals, improve resistance mitigation, and define optimal integration with other long-acting therapies.
4 July 2026
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