A5053439236- Statistical Methods in Clinical Trials
- Optimal Experimental Design Methods
- Statistical Methods and Bayesian Inference
- Alzheimer's disease research and treatments
- Health Systems, Economic Evaluations, Quality of Life
- Hemophilia Treatment and Research
- Analytical Chemistry and Chromatography
- Influenza Virus Research Studies
- Platelet Disorders and Treatments
- Biosimilars and Bioanalytical Methods
- Spectroscopy and Chemometric Analyses
- Anesthesia and Pain Management
- HIV Research and Treatment
- Pharmacogenetics and Drug Metabolism
- Cholinesterase and Neurodegenerative Diseases
- Peripheral Artery Disease Management
- Anesthesia and Sedative Agents
- Diagnosis and Treatment of Venous Diseases
- Anesthesia and Neurotoxicity Research
- Blood Coagulation and Thrombosis Mechanisms
- Advanced Causal Inference Techniques
- Respiratory viral infections research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Antibiotics Pharmacokinetics and Efficacy
- Statistical Methods and Inference
Roche (Switzerland)
2013-2024
Roche (France)
2013-2024
Bioanalytica (Switzerland)
2018
Inserm
2001-2011
Université Paris Cité
2007-2011
Délégation Paris 7
2009-2011
Hôpital Bichat-Claude-Bernard
2003-2010
Université Claude Bernard Lyon 1
2003-2010
Assistance Publique – Hôpitaux de Paris
2007-2010
Hôpital Beaujon
2008
Gantenerumab is a fully human monoclonal antibody that binds aggregated amyloid-β (Aβ) and removes Aβ plaques by Fc receptor-mediated phagocytosis. In the SCarlet RoAD trial, we assessed efficacy safety of gantenerumab in prodromal Alzheimer's disease (AD). this randomized, double-blind, placebo-controlled phase III study, investigated over 2 years. Patients were randomized to 105 mg or 225 placebo every 4 weeks subcutaneous injection. The primary endpoint was change from baseline week 104...
Although optimization of the fluoroquinolone dosage increases efficacy this class drugs against bacterial infections, its impact on emergence resistance in commensal bacteria is unknown.Six different 14-day dosages oral ciprofloxacin were randomly assigned to 48 healthy volunteers. Individual pharmacokinetic and pharmacodynamic parameters combining antibiotic exposure plasma, saliva, stool specimens minimum inhibitory concentrations (MICs) mutant prevention viridans group streptococci...
OBJECTIVE Peripheral arterial disease (PAD) is a prognostic marker in cardiovascular disease. The use of Doppler-measured ankle-brachial pressure index (Dop-ABI) for PAD diagnosis limited because time, required training, and costs. We assessed automated oscillometric measurement the (Osc-ABI) by nurses clinical staff. RESEARCH DESIGN AND METHODS Clinical staff obtained Osc-ABI with an device 146 patients (83 diabetes) at time Dop-ABI ultrasound evaluation. RESULTS Measurements were most legs...
We extend the development of expression Fisher information matrix in nonlinear mixed effects models for designs evaluation. consider dependence marginal variance observations with mean parameters and assume an heteroscedastic error model. Complex interoccasions variability quantifying influence covariates are introduced. Two methods using a Taylor expansion model around expectation random or simulated value, then Monte Carlo integration, proposed compared. Relevance resulting standard errors...
Abstract We extend the methodology for designs evaluation and optimization in nonlinear mixed effects models with an illustration of decrease human immunodeficiency virus viral load after antiretroviral treatment initiation described by a bi‐exponential model. first show relevance predicted standard errors (SEs) given computation population Fisher information matrix using R function PFIM, comparison to those computed stochastic approximation expectation–maximization algorithm, implemented...
Emicizumab is a bispecific monoclonal antibody developed for routine prophylaxis of bleeding in people with hemophilia A (PwHA). This work characterizes the pharmacokinetics emicizumab adult and pediatric PwHA, identifies factors contributing to its between-person variabilities, compares following different dosing regimens, makes descriptive assessment exposure–bleeding events relationship. population pharmacokinetic model was developed, using database 389 PwHA from five clinical studies....
Abstract We address the problem of choice and evaluation designs in population pharmacokinetic studies that use non‐linear mixed‐effects models. Criteria, based on Fisher information matrix, have been developed to optimize adapted such under different constraints evaluate them for a pharmacokinetics study, within new phase III trial enoxaparin, low molecular weight heparin. To do this, we approximate expression matrix models including residual error variance as parameter be estimated....
Emicizumab is a monoclonal antibody that bridges activated coagulation factor IX and X to restore effective hemostasis in persons with hemophilia A. It indicated for routine prophylaxis of bleeding episodes The aim the present study describe exposure-response relationship between emicizumab concentrations frequency, confirm adequate control investigated dosing regimens 1.5 mg/kg once weekly, 3 every 2 weeks, 6 4 weeks.
Abstract The Pharmpy Automatic Model Development (AMD) tool automates the building of population pharmacokinetic (popPK) models by utilizing a systematic stepwise process. In this study, performance AMD was assessed using simulated datasets. Ten true mimicking classical popPK were created. From each model, dataset replicates assuming typical phase I study design—single and multiple ascending doses with/without dichotomous food effect, with rich PK sampling. For every replicate, automatically...
Abstract We focus on the Fisher information matrix used for design evaluation and optimization in nonlinear mixed effects multiple response models. evaluate appropriateness of its expression computed by linearization as proposed a single model. Using pharmacokinetic–pharmacodynamic (PKPD) example, we first compare computation with approximation to one derived from observed large simulation using stochastic expectation–maximization algorithm (SAEM). The responses is also evaluated comparison...
Selecting the right dose is a significant challenge in designing clinical development programs, especially for slowly progressing diseases lacking predictive biomarkers of efficacy that may require long‐term treatment to assess benefit. Gantenerumab, fully human monoclonal antibody (mAb) binds aggregated amyloid‐beta, was tested two 24‐month phase III studies (NCT01224106, NCT02051608) participants with prodromal and mild Alzheimer’s disease (AD), respectively. Dosing first study suspended...
Aims A major concern with any antithrombotic therapy is an increase in the risk of haemorrhage. The aim this study was to analyse population pharmacokinetics and pharmacokinetic/pharmacodynamic (PK/PD) relationships for enoxaparin patients unstable angina (UA) non‐ST‐segment elevation myocardial infarction (NSTEMI), which may help predict Methods Anti‐factor Xa (anti‐Xa) activity measured as marker concentration 448 receiving drug a single 30‐mg intravenous bolus followed by 1.0 or 1.25 mg...
Abstract Baloxavir marboxil is an endonuclease inhibitor indicated for the treatment of influenza in patients ≥12 years. No data exist Chinese global studies. This randomized, open‐label, phase I study evaluated pharmacokinetics (PK) and safety baloxavir healthy volunteers was used to anticipate efficacy patients. Patients received a single oral dose (40 or 80 mg [1:1]). Serial blood samples were collected predose at various timepoints up 14 days postdose. acid plasma concentrations...