Evidence map›Paper›PMID 27767204›Full record

ArticleBritish journal of clinical pharmacology2017

Scaling clearance in paediatric pharmacokinetics: All models are wrong, which are useful?

Eva Germovsek, Charlotte I S Barker, Mike Sharland, Joseph F Standing

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Article in British journal of clinical pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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

72 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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  15. Strategies for pediatric dose derivation from population pharmacokinetic models.Journal of pharmacokinetics and pharmacodynamics · 2026
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12 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors.

Eva GermovsekInflammation, Infection and Rheumatology Section, Great Ormond Street Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK.
Charlotte I S BarkerInflammation, Infection and Rheumatology Section, Great Ormond Street Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK.
Mike SharlandPaediatric Infectious Diseases Research Group, Institute for Infection and Immunity, St George's, University of London, Cranmer Terrace, London, SW17 0RE, UK.
Joseph F StandingInflammation, Infection and Rheumatology Section, Great Ormond Street Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK.

Funding

Department of Health [UK]Medical Research Council G1002305Medical Research Council MR/M008665/1
6 · The paper itself

Abstract

linked articlesThis article is commented on in the editorial by Holford NHG and Anderson BJ. Why standards are useful for predicting doses. Br J Clin Pharmacol 2017; 83: 685-7. doi: 10.1111/bcp.13230

aimWhen different models for weight and age are used in paediatric pharmacokinetic studies it is difficult to compare parameters between studies or perform model-based meta-analyses. This study aimed to compare published models with the proposed standard model (allometric weight

methodsA systematic literature search was undertaken to identify published clearance (CL) reports for gentamicin and midazolam and all published models for scaling clearance in children. Each model was fitted to the CL values for gentamicin and midazolam, and the results compared with the standard model (allometric weight exponent of 0.75, along with a sigmoidal maturation function estimating the time in weeks of postmenstrual age to reach half the mature value and a shape parameter). For comparison, we also looked at allometric size models with no age effect, the influence of estimating the allometric exponent in the standard model and, for gentamicin, using a fixed allometric exponent of 0.632 as per a study on glomerular filtration rate maturation. Akaike information criteria (AIC) and visual predictive checks were used for evaluation.

resultsNo model gave an improved AIC in all age groups, but one model for gentamicin and three models for midazolam gave slightly improved global AIC fits albeit using more parameters: AIC drop (number of parameters), -4.1 (5), -9.2 (4), -10.8 (5) and -10.1 (5), respectively. The 95% confidence interval of estimated CL for all top performing models overlapped.

conclusionNo evidence to reject the standard model was found; given the benefits of standardised parameterisation, its use should therefore be recommended.

Indexed as

Models, BiologicalAge FactorsBody WeightChildGentamicinsHumansMidazolamPharmacokineticsGentamicinsMidazolamallometric exponentallometric scalingchildrengentamicininfantsmaturation functionmidazolamneonatesNONMEMpharmacometrics

Identifiers

PMID27767204
PMCPMC5346879

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Registered trials

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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.