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Record W4293698173 · doi:10.1111/bcp.15518

Comparative assessment of viral dynamic models for SARS‐CoV‐2 for pharmacodynamic assessment in early treatment trials

2022· article· en· W4293698173 on OpenAlexaff
Akosua Adom Agyeman, Tao You, Phylinda L. S. Chan, D Lonsdale, Christoforos Hadjichrysanthou, Tabitha Mahungu, Emmanuel Wey, David M. Lowe, Marc Lipman, Frank Kloprogge, Joseph F. Standing

Bibliographic record

VenueBritish Journal of Clinical Pharmacology · 2022
Typearticle
Languageen
FieldComputer Science
TopicComputational Drug Discovery Methods
Canadian institutionsInstitute of Infection and Immunity
FundersMedical Research Council
KeywordsViral loadPharmacodynamicsStatisticsBayesian information criterionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Coronavirus disease 2019 (COVID-19)Goodness of fitBayesian probabilityComputer scienceMedicineMathematicsImmunologyPharmacologyInternal medicinePharmacokineticsVirus

Abstract

fetched live from OpenAlex

Pharmacometric analyses of time series viral load data may detect drug effects with greater power than approaches using single time points. Because SARS‐CoV‐2 viral load rapidly rises and then falls, viral dynamic models have been used. We compared different modelling approaches when analysing Phase II‐type viral dynamic data. Using two SARS‐CoV‐2 datasets of viral load starting within 7 days of symptoms, we fitted the slope‐intercept exponential decay (SI), reduced target cell limited (rTCL), target cell limited (TCL) and TCL with eclipse phase (TCLE) models using nlmixr. Model performance was assessed via Bayesian information criterion (BIC), visual predictive checks (VPCs), goodness‐of‐fit plots, and parameter precision. The most complex (TCLE) model had the highest BIC for both datasets. The estimated viral decline rate was similar for all models except the TCL model for dataset A with a higher rate (median [range] day−1: dataset A; 0.63 [0.56–1.84]; dataset B: 0.81 [0.74–0.85]). Our findings suggest simple models should be considered during pharmacodynamic model development.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.019
metaresearch head score (Gemma)0.036
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Simulation or modeling · Consensus signal: Simulation or modeling
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.019
Threshold uncertainty score0.100

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0190.036
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0020.002
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0020.001
Open science0.0010.001
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.254
GPT teacher head0.583
Teacher spread0.329 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designSimulation or modeling
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations7
Published2022
Admission routes1
Has abstractyes

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