Evidence map›Paper›PMID 32737765›Full record

ArticleJournal of pharmacokinetics and pharmacodynamics2020

Well-tempered MCMC simulations for population pharmacokinetic models.

Frederic Y Bois, Nan-Hung Hsieh, Wang Gao, Weihsueh A Chiu, Brad Reisfeld

Open access · greenAbstract read
In one paragraph

Article in Journal of pharmacokinetics and pharmacodynamics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.5field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 11 citations in OpenAlex.

  1. Informatics for toxicokinetics.Journal of pharmacokinetics and pharmacodynamics · 2025
    Article
  2. Article
  3. Incorporating new approach methods (NAMs) data in dose-response assessments: The future is now!Journal of toxicology and environmental health. Part B, Critical reviews · 2025
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 4 institutions in 3 countries.

Frederic Y BoisCertara UK Limited, Simcyp Division, Sheffield, UK. frederic.bois@certara.com.ORCID 0000-0002-4154-0391
Nan-Hung HsiehDepartment of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA.
Wang GaoDRC/VIVA/METO Unit, INERIS, Verneuil en Halatte, France.
Weihsueh A ChiuDepartment of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA.
Brad ReisfeldDepartment Chemical and Biological Engineering, School of Biomedical Engineering, Colorado State University, Fort Collins, CO, USA.
Texas A&M University · USColorado State University · USInstitut national de l'environnement industriel et des risques · FRSimcyp (United Kingdom) · GB

Funding

Single cell, multi-parametric high throughput platform to classify endocrine disruptor potential of mixturesP42ES027704 · NIEHS · TEXAS A&M UNIVERSITY · PI Weihsueh A Chiu · 2017 to 2026
$21.2M
Enhancing the reliability, efficiency, and usability of Bayesian population PBPK modelingU01FD005838 · FDA · COLORADO STATE UNIVERSITY · PI REISFELD, BRAD · 2016 to 2017
$500k
FDA HHS U01 FD005838NIEHS NIH HHS P42 ES027704NIH HHS P42 ES027704U.S. Food and Drug Administration 1U01FD005838
6 · The paper itself

Abstract

A full Bayesian statistical treatment of complex pharmacokinetic or pharmacodynamic models, in particular in a population context, gives access to powerful inference, including on model structure. Markov Chain Monte Carlo (MCMC) samplers are typically used to estimate the joint posterior parameter distribution of interest. Among MCMC samplers, the simulated tempering algorithm (TMCMC) has a number of advantages: it can sample from sharp multi-modal posteriors; it provides insight into identifiability issues useful for model simplification; it can be used to compute accurate Bayes factors for model choice; the simulated Markov chains mix quickly and have assured convergence in certain conditions. The main challenge when implementing this approach is to find an adequate scale of auxiliary inverse temperatures (perks) and associated scaling constants. We solved that problem by adaptive stochastic optimization and describe our implementation of TMCMC sampling in the GNU MCSim software. Once a grid of perks is obtained, it is easy to perform posterior-tempered MCMC sampling or likelihood-tempered MCMC (thermodynamic integration, which bridges the joint prior and the posterior parameter distributions, with assured convergence of a single sampling chain). We compare TMCMC to other samplers and demonstrate its efficient sampling of multi-modal posteriors and calculation of Bayes factors in two stylized case-studies and two realistic population pharmacokinetic inference problems, one of them involving a large PBPK model.

Indexed as

Biological Variation, PopulationModels, BiologicalAcetaminophenAlgorithmsBayes TheoremHumansMarkov ChainsMonte Carlo MethodSoftwareTheophyllineAcetaminophenTheophyllineBayes factorBayesian inferencecomputational efficiencyphysiologically-based pharmacokinetic modelpopulation pharmacokineticsThermodynamic integration

Identifiers

PMID32737765
PMCPMC8082542
OpenAlexW3046770151

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.