The federated trials approach; an opportunity for global collaboration in health emergencies

EClinicalMedicine · 2026-02-25 · 1 citations

The gold standard for providing confirmatory evidence to regulatory agencies is a single sponsor conducting a randomised, controlled clinical trial (RCT). But emerging situations like the mpox outbreak can complicate launching large, single, global trials that meet the needs of multiple stakeholders, including multinational funders and regulators. Drawing on lessons from the mpox outbreak, we propose an alternative approach: the federated trial design. This approach ensures that individual trials launch quickly and that a rigorous, prespecified, conjoined analysis using combined data supports joint regulatory decisions. Early engagement with regulatory agencies is crucial to arranging such a conjoined analysis. Federating trials can support regulatory decision-making when they include a prespecified conjoined analysis that is sufficiently rigorous. Essential steps include harmonising individual trial protocols, aligning data standards, and arranging for a single Data Monitoring Committee to review a combined, multi-trial analysis. The classical single-trial approach remains the gold standard, but investigators should consider federated trials in emergencies that complicate conducting single trials. In such crises, investigators need to explain clearly why standalone evidence from participating RCTs is not obtainable. The federated trials design cannot replace the classical design, but can provide timely, robust evidence in crises such as public health emergencies.

Trends in Triple-Site Testing for Chlamydia and Gonorrhea in New York City: A Cross-sectional Study Using Health Information Exchange Data

Sexually Transmitted Diseases · 2026-03-19

BACKGROUND: Sexually transmitted infections (STIs) pose a threat to public health and continue to rise in New York City (NYC) despite reductions in other parts of the United States. Chlamydia and gonorrhea can infect multiple anatomic sites, including the urogenital tract, pharynx, and rectum. Guidelines recommend multisite testing for select populations, yet multisite testing is not routinely performed, limiting our understanding of trends in positivity and missed infections. METHODS: We conducted a retrospective cross-sectional study of patients who underwent triple-site testing for chlamydia and gonorrhea in NYC between January 2018 and June 2023 using data from Healthix, the largest public health information exchange (HIE) in the country. We examined rates of triple-site testing, the prevalence of positivity at any anatomic site, and the proportion of extragenital-only positivity. We fit logistic regression models using generalized estimating equations to identify predictors of triple-site testing as well as overall and extragenital-only positivity. RESULTS: We identified 11,405 individuals who received triple-site testing during the study period, representing 28,565 triple-site tests, 2,742 chlamydia cases, and 2,702 gonorrhea cases. The rectum was the most common site of infection for both STIs. Overall, 82% of chlamydia infections (82% in men and 77% in women) and 86% of gonorrhea infections (86% in men and 87% in women) would have been missed with urogenital-only testing. CONCLUSIONS: In this cross-sectional study of HIE data, we examined citywide testing and found that, among patients undergoing triple-site testing, the majority of chlamydia and gonorrhea cases would have been missed through urogenital-only testing.

Sexually transmissible infections affecting the gastrointestinal tract: what gastroenterologists and hepatologists need to know

Apollo (University of Cambridge) · 2025-11-12

Sexually transmissible gastrointestinal (enteric) infections cause oropharyngitis, hepatitis, enteritis, proctocolitis and anorectal disease, and can mimic neoplastic and inflammatory gastrointestinal disease. Sexually transmissible enteric infections are generally seen in men who have sex with men (MSM) due to sexual behaviours which risk faecal-oral transmission. Oropharyngeal and anorectal sexually transmitted infections (STIs) are transmitted via direct inoculation from oral and anal sexual behaviours. Shigella spp, Campylobacter spp, Salmonella spp, diarrhoeagenic Escherichia coli , Giardia duodenalis and Entamoeba histolytica are recognised sexually transmissible enteric faeco-oral pathogens in MSM. Neisseria gonorrhoeae , Chlamydia trachomatis, herpes simplex virus (HSV), Treponema pallidum subspecies pallidum (Syphilis), mpox and HSV cause sexually transmissible oropharyngeal and anorectal disease. Cryptosporidium, intestinal spirochaetosis , Blastocystis, Strongyloides stercoralis, Enterobius vermicularis and enteric viruses have infrequently been reported as sexually transmissible in MSM. Sexually transmissible enteric infections have increased in MSM over the past 35 years. Gastroenterologists and hepatologists do not generally enquire about sexual behaviours, but identifying sexually transmissible enteric infections is important due to high rates of bacterial antimicrobial resistance, and the additional management includes: bacterial antimicrobial susceptibility testing, testing for STIs/HIV, providing recommendations for sexual abstinence and partner notification; and onward referral to specialist sexual health clinics for sexual health prevention interventions. In this review, we highlight the STIs which can affect the gastrointestinal tract and provide some key management points for gastroenterologists and hepatologists.

Correlates of asymptomatic sexually transmitted infections among marginalized women in the Dominican Republic

International Journal of STD & AIDS · 2025-10-21

BackgroundSexually transmitted infections (STIs) continue to cause morbidity among women in resource-constrained settings, where asymptomatic infections are often overlooked due to syndromic management protocols. We investigated correlates of asymptomatic STIs among women in the Dominican Republic (DR).MethodsWe analyzed data collected from cisgender women in DR between 2015 and 2019. Classified groups included pregnant youth (PY), people with HIV (PWH), residents of bateyes (RB), and sex workers (SW). Nucleic acid amplification or rapid plasma reagin tests detected STIs (Chlamydia/Gonorrhoeae/Syphilis/Trichomonas). Asymptomatic comprised no self-reported vaginal discharge, dysuria, groin lymphadenopathy, and genital/anal pain/ulcers. Logistic regressions identified sociodemographic, clinical, and behavioral correlates.ResultsAmong 833 asymptomatic women (median age 29, IQR 19-37), 35% were PY, 27% PWH, 11% RB, and 27% SW. STI prevalence was 24%: most (61%) had Chlamydia and few (≤25%) had Gonorrhoea, Syphilis, or Trichomonas. Asymptomatic STI correlates included age ≤24 (Adjusted Odds Ratio [aOR] = 2.32, [1.65-3.28]), early (≤14) sexual debut (aOR = 1.56, [1.11-2.18]), greater mobility (aOR = 1.41, [1.01-1.97]), lack of regular doctor (aOR = 1.42, [1.01-1.99]), and drug use in last 6 months (aOR = 1.88, [1.07-3.26]).ConclusionsCorrelates of asymptomatic STIs-age, sexual debut, mobility, healthcare access, and drug use-should inform targeted screening and prevention efforts where diagnostic testing is not widely available.

Clinical Outcomes of Mpox Disease in Patients Treated With Tecovirimat

Clinical Infectious Diseases · 2025-09-18

BACKGROUND: There is emerging literature describing clinical characteristics and outcomes in patients with mpox treated with tecovirimat. METHODS: We analyzed retrospective deidentified data from healthcare systems in New York City with the highest number of tecovirimat prescriptions. Individuals with probable or confirmed mpox initiating tecovirimat from May to December 2022 were included. A chart abstraction instrument was used to extract demographic and clinical data from medical records. We examined factors associated with delay in treatment and hospitalization. RESULTS: A total of 708 individuals prescribed tecovirimat for mpox were included in the analysis; median age was 36 years (IQR 31-43); 566 (80%) were cisgender men who have sex with men; and 399 (56%) were diagnosed with HIV. Side effects (100, 14%) and severe adverse events (7, 1%) were rare. The most common long-term sequela was scarring (69, 10%). One hundred and one (14%) were hospitalized. Median time from symptom onset to treatment initiation was 8 days (IQR 6-11). Non-Hispanic Black patients had higher risk of initiating tecovirimat ≥8 days after symptom onset (relative risk [RR] = 1.3, 95% CI: 1.2-1.7) and being hospitalized (adjusted relative risk [aRR] = 2.2, 95% CI: 1.4-3.5) compared with Hispanic patients, after adjusting for HIV and insurance status. CONCLUSIONS: We described common reasons for tecovirimat initiation and hospitalization. There were racial inequities in hospitalization and treatment delays. More research and focused efforts to mitigate these inequities are needed. These findings may better inform decisions for treatment initiation and hospitalization for mpox.

The Design Process of a Digital Patient Decision Tool to Increase Sexually Transmitted Infection Testing in the Emergency Department

Sexually Transmitted Diseases · 2025-06-04 · 2 citations

BACKGROUND: Adolescents and young adults (AYA) frequently use the emergency department (ED) and admit to infrequent contraceptive use, increasing their risk of sexually transmitted infections (STIs). This study aimed to design STI Check in the Emergency Room (STIckER), a user-informed digital patient decision aid aiming to increase shared decision making around genitourinary and extragenital STIs testing among AYA ED patients. METHODS: This 2-center study followed a multiphase approach. In phase 1, we defined our health condition, target audience, and health decision, and organized a multidisciplinary steering group. Through a series of design workshops, we created a low-fidelity prototype. In phase 2, we conducted semistructured interviews with AYA ED patients and ED health care providers to understand values and preferences around STI testing and decision-aid implementation. Interviews were recorded and analyzed using rapid qualitative analysis techniques. Data from interviews led to a final high-fidelity prototype. RESULTS: Interviews with 19 AYA ED patients suggested interest in participating in the decision for STI testing and have emotions about getting results. Interviews with 15 ED health care providers highlighted that shared decision making matches clinical practice, interventions should not increase cognitive load, and sexual health interventions are more complex when parents are involved. Both groups were receptive to nonjudgmental sexual health interventions that promote privacy and eliminate testing stigma. CONCLUSION: The STIckER decision aid was designed using an iterative process that involved user testing and integrating feedback, leading to a digital tool that could promote equitable STI testing built specifically for the complex ED setting.

Development of machine learning-based mpox surveillance models in a learning health system

Sexually Transmitted Infections · 2025-05-02 · 3 citations

OBJECTIVES: This study aimed to develop robust machine learning (ML)-based and deep learning (DL)-based models capable of detecting mpox cases for surveillance efforts using clinical notes. METHODS: As part of a learning health system initiative, we conducted a retrospective study of clinical encounters at the Columbia University Irving Medical Center in New York City. We included patients with mpox diagnoses confirmed by PCR testing between 15 May 2022 and 15 October 2022 and three matched controls for each case based on patient age, sex, race, ethnicity and visit month. We trained three mpox surveillance models using: (1) logistic regression with L1 regularisation (least absolute shrinkage and selection operator (LASSO)), (2) ClinicalBERT and (3) ClinicalLongformer. We evaluated model performance using precision, recall, F1 score, area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC) and recall at 80% precision (RP80). RESULTS: The study included 228 PCR-confirmed mpox cases and 698 controls. LASSO regression outperformed the DL models with a precision, recall and F1 score of 0.93, AUROC of 0.97, AUPRC of 0.93 and RP80 of 0.89. ClinicalBERT achieved a precision of 0.88, recall of 0.89, F1 score of 0.88 and AUROC of 0.93. ClinicalLongformer achieved a precision of 0.87, recall of 0.88, F1 score of 0.87 and AUROC of 0.92. Phrases related to symptoms (eg, lesions and pain) were among the most predictive features in LASSO regression. CONCLUSIONS: ML and DL models based on clinical notes show promise for identifying mpox cases. In this study, LASSO regression outperformed DL models and excelled in minimising false positives. These findings highlight the potential for ML and DL methods to support case surveillance for mpox and other infectious diseases. These methods may also prove helpful for flagging missed or delayed diagnoses as part of continuous quality improvement.

Identifying Provider Attitudes, Practices, and Barriers to Extra-Genital Testing for Neisseria Gonorrheae and Chlamydia Trachomatis Infections Among Adolescents and Young Adults

Journal of Adolescent Health · 2025-04-03 · 2 citations

Hospital wastewater surveillance for SARS-CoV-2 identifies intra-hospital dynamics of viral transmission and evolution

medRxiv · 2025-03-05 · 1 citations

Abstract Wastewater testing has emerged as an effective, widely used tool for population-level SARS-CoV-2 surveillance. Such efforts have primarily been implemented at the wastewater treatment plants (WWTPs), providing data for large resident populations but hindering the ability to implement targeted interventions or follow-ups. Conversely, building-level wastewater data exhibits increased variability due to rapid daily population dynamics but allows for targeted follow-up interventions or mitigation efforts. Here, we implemented a three-site wastewater sampling strategy on our university-affiliated medical campus from May 2021 to March 2024, comprised of two distinct hospital quadrants and a primarily research laboratory and classroom building. We first addressed several limitations in implementing hospital-level wastewater surveillance by optimizing sampling frequency and laboratory techniques. We subsequently improved our ability to model SARS-CoV-2 case counts using wastewater data by performing sensitivity analyses on viral shedding assumptions and testing the utility of internal normalization factors for population size. Our unique infrastructure allowed us to detect intra-hospital dynamics of SARS-CoV-2 prevalence and diversity and confirmed that direct sequencing of wastewater was able to capture corresponding clinical viral diversity. In contrast, research building wastewater sampling showed that for most non-residential settings, despite low overall viral loads, a threshold approach can still be used to identify peaks in cases or transmission amongst the general population. Our study expands on current wastewater surveillance practices by examining the utility of and best practices for upstream and particularly hospital settings, enabling the use of non-municipal, medium-scale wastewater testing to inform efforts for reducing the burden of COVID-19. Importance Since the onset of the COVID-19 pandemic, wastewater surveillance has been increasingly implemented to track the spread of SARS-CoV-2. Most wastewater testing across the United States occurs at municipal wastewater treatment plants. Yet, this testing method could also be beneficial at non-municipal and non-residential sites, including hospitals, where wastewater data for SARS-CoV-2 signals and viral diversity could directly impact hospital practices to control its spread. We analyzed both hospital and non-residential research building wastewater over a three-year period to establish optimized methods for collecting and interpreting wastewater data at sites upstream of treatment plants. We found that even within a single hospital building, wastewater testing in different locations showed distinct signatures over time, which corresponded with data from patients hospitalized in those locations. This study provides a framework for the use of wastewater viral surveillance upstream of municipal treatment plants to enable targeted interventions to limit the spread of SARS-CoV-2.

Population pharmacokinetics of tecovirimat in persons with mpox: Initial results from ACTG A5418

British Journal of Clinical Pharmacology · 2025-09-01

1 Background: The Study of Tecovirimat for Human Mpox Virus (STOMP) (ACTG A5418) assessed the safety, efficacy and pharmacokinetics (PK) of tecovirimat in clade II mpox infection. We previously showed lower tecovirimat exposures among participants in the open-label arm in comparison to healthy volunteers (HVs), though predicted concentrations at the end of the dosing interval (Ctau) were comparable or above the therapeutic target in non-human primates (NHPs). In clinical trials, tecovirimat did not reduce time to clinical resolution vs. placebo, highlighting the need to examine factors affecting tecovirimat PK in persons with mpox and the adequacy of current dosing strategies. Here, we report the initial population PK modelling of tecovirimat in persons with mpox and comparisons with historical data in HVs. Methods: Participants in the randomized and open-label arms received oral tecovirimat 600 mg either twice daily (weight 40–<120 kg) or three times daily (weight ≥120 kg) for 14 days. Intensive PK sampling occurred on treatment Day 8 at time 0 (pre-dose) and 1, 2, 3, 4, 6, 8 and 10 h post-dose with sparse sampling on Days 3, 8 and/or 15. Plasma tecovirimat concentrations were quantified by a validated LC–MS/MS assay. The population PK model was developed in Phoenix NLME. One- and two- compartment models with additive, multiplicative, or combined error models were investigated. Fixed allometric scaling of weight on apparent volume of distribution (V/F) and apparent oral clearance (CL/F), inclusion of an absorption lag time (Tlag) and the effect of meals on relative bioavailability (F) and absorption rate (ka) were assessed in base model development in alignment with prior modelling in HVs. Simulations with 100 replicates per participant were performed with the final base model, and predicted AUC0-24h, Cmax and Ctau estimates were compared to those previously simulated in HVs (US FDA Clinical Pharmacology Review) and the NHP therapeutic target (169 ng/mL). Results: PK data were available in 75 participants (41 participants with 315 intensive+30 sparse observations; 34 participants with 59 sparse observations; 404 observations total). A one-compartment model with combined error, Tlag and allometric scaling for weight (centred to 70 kg) fixed at 1 and 0.75 on V/F and CL/F, respectively, best fit the available data. Population estimates (95% CI) for ka, Tlag, V/F and CL/F were 0.56 1/h (0.20–0.92), 0.99 h (0.91–1.07), 367 L (222–510) and 51.6 L/h (44.7–58.5), respectively. Interindividual variability for ka, Tlag, V/F and CL/F were 124%, 57.6%, 65.9% and 42.7%, respectively, and generally indicated more variability than HVs. Median simulated AUC0-24h, Cmax and Ctau were 38.8%, 38.5% and 36.4% lower in A5418 participants than HVs. Simulated median Ctau (5th, 95th percentiles) was 599 ng/mL (112, 1523) in A5418 participants, with 8.5% of predicted Ctau values from A5418 falling below the NHP therapeutic target. Conclusions: Lower tecovirimat exposures and greater PK variability were observed in A5418 participants vs. HVs, but simulated Ctau estimates exceeded the NHP therapeutic target in ~91.5% of cases. Investigation into the mechanism of these differences and their relationship to clinical/virologic outcomes is warranted.