eprintid: 10117964
rev_number: 28
eprint_status: archive
userid: 608
dir: disk0/10/11/79/64
datestamp: 2021-01-18 17:41:24
lastmod: 2021-12-06 00:06:20
status_changed: 2021-01-18 17:41:24
type: article
metadata_visibility: show
creators_name: Wasmann, RE
creators_name: Svensson, EM
creators_name: Walker, AS
creators_name: Clements, MN
creators_name: Denti, P
title: Constructing a representative in-silico population for paediatric simulations: Application to HIV-positive African children
ispublished: inpress
divisions: UCL
divisions: B02
divisions: D65
divisions: J38
keywords: modelling, paediatric population, pharmacokinetics-pharmacodynamics, simulation, underweight, weight-for-age
note: © 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/).
abstract: AIMS: Simulations are an essential tool for investigating scenarios in pharmacokinetics-pharmacodynamics. The models used during simulation often include the effect of highly correlated covariates such as weight, height and sex, and for children also age, which complicates the construction of an in silico population. For this reason, a suitable and representative patient population is crucial for the simulations to produce meaningful results. For simulation in paediatric patients, international growth charts from the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) provide a reference, but these may not always be representative for specific populations, such as malnourished children with HIV or acutely unwell children. METHODS: We present a workflow to construct a virtual paediatric patient population using WHO and CDC growth charts, suggest piecewise linear functions to adjust the median of the growth charts by sex and age, and suggest visual diagnostics to compare with the target population. We applied this workflow in a population of 1206 HIV-positive African children, consisting of 19 742 observations with weight ranging from 3.8 to 79.7 kg, height from 55.5 to 180 cm, and an age between 0.40 and 18 years. RESULTS: Before adjustment, the WHO and CDC charts produced weights and heights higher compared to the observed data. After applying our methodology, we could simulate weight, height, sex and age combinations in good agreement with the observed data. CONCLUSION: The methodology presented here is flexible and may be applied to other scenarios where WHO and CDC growth standards might not be appropriate. In addition we provide R scripts and a large ready-to-use paediatric population.
date: 2021-01-11
date_type: published
official_url: https://doi.org/10.1111/bcp.14694
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1838188
doi: 10.1111/bcp.14694
lyricists_name: Clements, Michelle
lyricists_name: Walker, Ann
lyricists_id: MNCLE87
lyricists_id: ASWAL40
actors_name: Walker, Ann
actors_id: ASWAL40
actors_role: owner
full_text_status: public
publication: British Journal of Clinical Pharmacology
event_location: England
citation:        Wasmann, RE;    Svensson, EM;    Walker, AS;    Clements, MN;    Denti, P;      (2021)    Constructing a representative in-silico population for paediatric simulations: Application to HIV-positive African children.                   British Journal of Clinical Pharmacology        10.1111/bcp.14694 <https://doi.org/10.1111/bcp.14694>.    (In press).    Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10117964/13/Walker_Constructing%20a%20representative%20in-silico%20population%20for%20paediatric%20simulations-%20Application%20to%20HIV-positive%20African%20children_AOP.pdf