A5003225431- Statistical Methods in Clinical Trials
- Optimal Experimental Design Methods
- Health Systems, Economic Evaluations, Quality of Life
- Social Sciences and Governance
- Neonatal Respiratory Health Research
- Meta-analysis and systematic reviews
- Statistical Methods and Bayesian Inference
- Advanced Causal Inference Techniques
- Statistical Methods and Inference
- Pharmacogenetics and Drug Metabolism
- Bayesian Methods and Mixture Models
- Pharmaceutical studies and practices
- Infant Development and Preterm Care
- Computational Drug Discovery Methods
- Colorectal Cancer Screening and Detection
- Long-Term Effects of COVID-19
- Childhood Cancer Survivors' Quality of Life
- Biosimilars and Bioanalytical Methods
- COVID-19 Clinical Research Studies
- Congenital Heart Disease Studies
- Delphi Technique in Research
- Cardiovascular Conditions and Treatments
- Colorectal Cancer Treatments and Studies
- Asthma and respiratory diseases
- Genomic variations and chromosomal abnormalities
Inserm
2016-2025
Sorbonne Université
2016-2025
Université Paris Cité
2016-2025
Centre de Recherche des Cordeliers
2018-2025
French Clinical Research Infrastructure Network
2018-2025
Hôpital Robert-Debré
2023-2025
Institut national de recherche en informatique et en automatique
2022-2025
Assistance Publique – Hôpitaux de Paris
2021-2025
Sorbonne Paris Cité
2019-2025
University of Naples Federico II
2025
Objectives: About 5% of patients with coronavirus disease-2019 are admitted to the ICU for acute hypoxemic respiratory failure. Opinions differ on whether invasive mechanical ventilation should be used as first-line therapy over noninvasive oxygen support. The aim study was assess effect early in failure day-60 mortality. Design: Multicenter prospective French observational study. Setting: Eleven ICUs OutcomeRea network. Patients: Coronavirus (Pa o 2 /F io ≤ 300 mm Hg), without shock or...
The aim of phase I clinical trials is to obtain reliable information on safety, tolerability, pharmacokinetics (PK), and mechanism action drugs with the objective determining maximum tolerated dose (MTD). In most studies, dose-finding PK analysis are done separately no attempt made combine them during allocation. cases such as rare diseases, paediatrics, studies in a biomarker-defined subgroup defined population, available population size will limit number possible that can be conducted....
Objectives In severe COVID-19 pneumonia, the appropriate timing and dosing of corticosteroids (CS) is not known. Patient subgroups for which CS could be more beneficial also need appraisal. The aim this study was to assess effect early in pneumonia patients admitted ICU on occurrence 60-day mortality, ICU-acquired-bloodstream infections(ICU-BSI), hospital-acquired ventilator-associated pneumonia(HAP-VAP). Methods We included with 11 ICUs belonging French OutcomeRea TM network from January...
The CONSORT (CONsolidated Standards Of Reporting Trials) 2010 statement is the standard guideline for reporting completed randomised trials. Dose-finding Extension (DEFINE) extends guidance (with 21 new items and 19 modified items) to early phase dose-finding trials with interim dose escalation or de-escalation strategies. Such generally focus on safety, tolerability, activity, recommending dosing scheduling regimens further clinical development. These are often inadequately reported,...
SummaryEarly phase dose-finding (EPDF) trials are key in the development of novel therapies, with their findings directly informing subsequent clinical phases and providing valuable insights for reverse translation. Comprehensive transparent reporting these studies is critical accurate interpretation, which may improve expedite therapeutic development. However, quality design characteristics results from EPDF often variable incomplete. The international consensus-based CONSORT-DEFINE...
Abstract Objective This study aimed to evaluate the effects of intravaginal prasterone treatment on urge urinary symptoms in women affected by genitourinary syndrome menopause. Methods The was conducted postmenopausal with vulvovaginal atrophy and increased frequency urgency an Overactive Bladder Screener score >8. Participants underwent urodynamic examination completed International Consultation Incontinence Questionnaire—Short Form (ICIQ-SF) questionnaire before after 3 months...
Persistent patency of the ductus arteriosus (PDA) has challenged neonatologists for more than 40 years. Controversies persist about management PDA in extremely preterm infants. is associated with morbidities, but no therapeutic strategy resulted an improved neonatal outcome. Acetaminophen appears to be a promising alternative possibly fewer adverse effects. The primary objective determine whether prophylactic pharmacological intervention acetaminophen may increase survival without severe...
During drug evaluation trials, information from clinical trials previously conducted on another population, indications or schedules may be available. In these cases, it might desirable to share by efficiently using the available resources. this work, we developed an adaptive power prior with a commensurability parameter for historical external information. It allows, at each stage, full borrowing when data are not in conflict, no conflict “tuned” between. We propose apply our method...
SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 provides guidance clinical trial protocol writing. However, neither the original nor its extensions adequately cover features of early phase dose-finding trials. The Dose-finding Extension (DEFINE) statement is a new guideline that recommendations essential items should be provided in protocols these It details to guidance, incorporating 17 and modifying 15 existing items. purpose this promote transparency,...
Although antenatal betamethasone is recommended worldwide for women at risk of preterm delivery, concerns persist regarding the long-term effects associated with this treatment. Indeed, adverse events, mainly dose-related, have been reported. The current dose directly derives from sheep experiments performed in late 60's and has not challenged 45 years. Therefore, randomized trials evaluating novel regimens are urgently needed.A randomised, double blind, placebo-controlled, non-inferiority...
While the SARS-CoV-2 (COVID-19) pandemic has led to an impressive and unprecedented initiation of clinical research, it also considerable disruption trials in other disease areas, with around 80% non-COVID-19 stopped or interrupted during pandemic. In many cases disrupted will not have planned statistical power necessary yield interpretable results. This article describes methods compensate for information loss arising from trial disruptions by incorporating additional available auxiliary...
Antenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, its optimal dose remains unknown. A 50% reduction was proposed decrease the potential dose-related long-term neurodevelopmental side effects, including psychological development, sleep, and emotional disorders. Because noninferiority of half in terms need for exogenous surfactant not shown primary analysis, impact on survival without major neonatal morbidity needs be investigated.
In this paper, a new discrete statistical model for ordered categorical data is proposed via fixed-point discretization of beta latent variable. The resulting discretized distribution has highly flexible shape and it can be either over-dispersed or under-dispersed with respect to the binomial distribution. It only two parameters, which may therefore parsimoniously depend on covariates random effects, providing tools analysis structured, clustered longitudinal ordinal data. Practical examples...
The number of trials conducted and the patients per trial are typically small in paediatric clinical studies. This is due to ethical constraints complexity medical process for treating children. While incorporating prior knowledge from adults may be extremely valuable, this must done carefully. In paper, we propose a unified method designing analysing dose-finding paediatrics, while bridging information adults. dose-range calculated under three extrapolation options, linear, allometry...
Phase I dose-finding trials in oncology seek to find the maximum tolerated dose (MTD) of a drug under specific schedule. Evaluating drug-schedules aims at improving treatment safety while maintaining efficacy. However, we can reasonably assume that toxicity increases with for cytotoxic drugs, relationship between and multiple schedules remains elusive. We proposed Bayesian dose-regimen assessment method (DRtox) using pharmacokinetics/pharmacodynamics (PK/PD) information estimate...
Background Satisfactory treatment is often lacking for spasticity, a highly prevalent motor disorder in patients with spinal cord injury (SCI). Low concentrations of riluzole potently reduce the persistent sodium current, post-SCI increase which contributes to spasticity. The repurposing this drug may therefore constitute useful potential therapeutic option relieving SCI suffering from chronic traumatic Objective RILUSCI phase 1b–2b trial designed assess whether safe and biologically...
This article addresses the concern regarding late-onset dose-limiting toxicities (DLT), moderate below threshold of a DLT and cumulative that may lead to DLT, which are mostly disregarded or handled in an ad hoc manner when determining maximum tolerated dose (MTD) dose-finding cancer clinical trials. An extension Time-to-Event Continual Reassessment Method (TITE-CRM) allows for specification toxicity constraints on both toxicities, can account partial information is proposed. The method...
Introduction Therapeutic schedules for treating neonatal seizures remain elusive. First-line treatment with phenobarbital is widely supported but without strong scientific evidence. Levetiracetam (LEV) an emerging and promising antiepileptic drug (AED). The aim of this phase II trial to determine the benefits LEV by applying a strict methodology estimate optimal dose as first-line AED treat in newborns suffering from hypoxic-ischaemic encephalopathy. Methods analysis LEVNEONAT-1 open...
The mortality of COVID-19 patients in the intensive care unit (ICU) is influenced by their state at admission. We aimed to model acute respiratory distress syndrome transitions from ICU admission day 60 outcome and evaluate possible prognostic factors. analyzed a prospective French database that includes critically ill patients. A six-state multistate was built 17 were either using non-parametric approach or Cox proportional hazard model. Corticosteroids IL-antagonists (tocilizumab anakinra)...
We congratulate the authors for new meta-analysis model that accounts different outcomes. discuss modeling choice and Bayesian setting, specifically, we point out connection between hierarchical a mixed-effect formulation to subsequently possible future method extensions.