ArticleJournal of pharmacokinetics and pharmacodynamics2014
Evaluation of bootstrap methods for estimating uncertainty of parameters in nonlinear mixed-effects models: a simulation study in population pharmacokinetics.
Article in Journal of pharmacokinetics and pharmacodynamics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
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- PK/PD modeling of a clazosentan thorough QT study with hysteresis in concentration-QT and RR-QT.Journal of pharmacokinetics and pharmacodynamics · 2021Trial
- A Pharmacometric Approach to Substitute for a Conventional Dose-Finding Study in Rare Diseases: Example of Phase III Dose Selection for Emicizumab in Hemophilia A.Clinical pharmacokinetics · 2018Trial
- Population pharmacokinetics of imipenem in critically ill patients with suspected ventilator-associated pneumonia and evaluation of dosage regimens.British journal of clinical pharmacology · 2014Trial
- Kinetic Analysis of Irreversible Covalent Enzyme Inhibitors and Its Use in Drug Design.International journal of molecular sciences · 2026Review
- Assessing Covariate Clinical Relevance in High-Dimensional PK Analysis: A Comparison of SCM+, FFEM, and FREM Approaches.CPT: pharmacometrics & systems pharmacology · 2026Article
- Associations between multidimensional fatigue and wearable-derived cardio-respiratory variables in post-COVID-19 patients: an observational study.Frontiers in digital health · 2026Article
- Establishment of a Vancomycin Population Pharmacokinetic Model for Pediatric Patients Based on the Non-Linear Mixed-Effects Model.Drugs in R&D · 2025Article
- Impact of covariate model building methods on their clinical relevance evaluation in population pharmacokinetic analyses: comparison of the full model, stepwise covariate model (SCM) and SCM+ approaches.Journal of pharmacokinetics and pharmacodynamics · 2024Article
- Population Pharmacokinetics of Cabozantinib in Metastatic Renal Cell Carcinoma Patients: Towards Drug Expenses Saving Regimens.Clinical pharmacokinetics · 2024Article
- Uncertainty Computation at Finite Distance in Nonlinear Mixed Effects Models-a New Method Based on Metropolis-Hastings Algorithm.The AAPS journal · 2024Article
- Accelerating drug development for amyotrophic lateral sclerosis: construction and application of a disease course model using historical placebo group data.Orphanet journal of rare diseases · 2024Article
- An improved PKPD modeling approach to characterize the pharmacodynamic interaction over time between ceftazidime/avibactam and colistin fromAntimicrobial agents and chemotherapy · 2023Article
- Safety Evaluation and Population Pharmacokinetics of Camostat Mesylate and Its Major Metabolites Using a Phase I Study.Pharmaceutics · 2023Article
- The Effect of Stereotactic Body Radiation Therapy for Hepatocellular Cancer on Regional Hepatic Liver Function.International journal of radiation oncology, biology, physics · 2023Article
- Population Pharmacokinetics of Isavuconazole in Critical Care Patients with COVID-19-Associated Pulmonary Aspergillosis and Monte Carlo Simulations of High Off-Label Doses.Journal of fungi (Basel, Switzerland) · 2023Article
- Increasing transparency in machine learning through bootstrap simulation and shapely additive explanations.PloS one · 2023Article
- Population Pharmacokinetics of Oral Brepocitinib in Healthy Volunteers and Patients.Clinical pharmacology in drug development · 2022Article
- Longitudinal and time-to-event modeling for prognostic implications of radical surgery in retroperitoneal sarcoma.CPT: pharmacometrics & systems pharmacology · 2022Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bootstrap methods are used in many disciplines to estimate the uncertainty of parameters, including multi-level or linear mixed-effects models. Residual-based bootstrap methods which resample both random effects and residuals are an alternative approach to case bootstrap, which resamples the individuals. Most PKPD applications use the case bootstrap, for which software is available. In this study, we evaluated the performance of three bootstrap methods (case bootstrap, nonparametric residual bootstrap and parametric bootstrap) by a simulation study and compared them to that of an asymptotic method (Asym) in estimating uncertainty of parameters in nonlinear mixed-effects models (NLMEM) with heteroscedastic error. This simulation was conducted using as an example of the PK model for aflibercept, an anti-angiogenic drug. As expected, we found that the bootstrap methods provided better estimates of uncertainty for parameters in NLMEM with high nonlinearity and having balanced designs compared to the Asym, as implemented in MONOLIX. Overall, the parametric bootstrap performed better than the case bootstrap as the true model and variance distribution were used. However, the case bootstrap is faster and simpler as it makes no assumptions on the model and preserves both between subject and residual variability in one resampling step. The performance of the nonparametric residual bootstrap was found to be limited when applying to NLMEM due to its failure to reflate the variance before resampling in unbalanced designs where the Asym and the parametric bootstrap performed well and better than case bootstrap even with stratification.
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