ArticlePharmaceutical research2016
Enhanced Method for Diagnosing Pharmacometric Models: Random Sampling from Conditional Distributions.
Article in Pharmaceutical research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed.
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- Modeling serum M-protein response for early detection of biochemical relapse in myeloma patients treated with bortezomib, lenalidomide and dexamethasone.CPT: pharmacometrics & systems pharmacology · 2024Article
- Prediction of Individual Disease Progression Including Parameter Uncertainty in Rare Neurodegenerative Diseases: The Example of Autosomal-Recessive Spastic Ataxia Charlevoix Saguenay (ARSACS).The AAPS journal · 2024Article
- Model-based simulation to support the approval of isatuximab alone or with dexamethasone for the treatment of relapsed/refractory multiple myeloma in Japanese patients.CPT: pharmacometrics & systems pharmacology · 2023Article
- Negative Impact of ST-Segment Elevation Myocardial Infarction and Morphine Dose on Ticagrelor Uptake and Pharmacodynamics: A Population PK/PD Analysis of Pooled Individual Participant Data.Clinical pharmacokinetics · 2023Article
- Plasma pharmacokinetics of tigolaner, emodepside, and praziquantel following topical administration of a combination product (Felpreva®) and of intravenous administration of the individual active ingredients in cats.Current research in parasitology & vector-borne diseases · 2023Article
- Pharmacokinetics and Dose Optimization Strategies of Para-Aminosalicylic Acid in Children with Rifampicin-Resistant Tuberculosis.Antimicrobial agents and chemotherapy · 2022Article
- Population pharmacokinetic analysis of dexmedetomidine in children using real-world data from electronic health records and remnant specimens.British journal of clinical pharmacology · 2022Article
- "De-Shrinking" EBEs: The Solution for Bayesian Therapeutic Drug Monitoring.Clinical pharmacokinetics · 2022Article
- Joint modelling and simulation of M-protein dynamics and progression-free survival for alternative isatuximab dosing with pomalidomide/dexamethasone.British journal of clinical pharmacology · 2022Article
- SAMBA: A novel method for fast automatic model building in nonlinear mixed-effects models.CPT: pharmacometrics & systems pharmacology · 2022Article
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeFor nonlinear mixed-effects pharmacometric models, diagnostic approaches often rely on individual parameters, also called empirical Bayes estimates (EBEs), estimated through maximizing conditional distributions. When individual data are sparse, the distribution of EBEs can "shrink" towards the same population value, and as a direct consequence, resulting diagnostics can be misleading.
methodsInstead of maximizing each individual conditional distribution of individual parameters, we propose to randomly sample them in order to obtain values better spread out over the marginal distribution of individual parameters.
resultsWe evaluated, through diagnostic plots and statistical tests, hypothesis related to the distribution of the individual parameters and show that the proposed method leads to more reliable results than using the EBEs. In particular, diagnostic plots are more meaningful, the rate of type I error is correctly controlled and its power increases when the degree of misspecification increases. An application to the warfarin pharmacokinetic data confirms the interest of the approach for practical applications.
conclusionsThe proposed method should be implemented to complement EBEs-based approach for increasing the performance of model diagnosis.
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