{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:32:32Z","timestamp":1785414752044,"version":"3.56.0"},"reference-count":13,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Simulations are an essential tool for investigating scenarios in pharmacokinetics\u2010pharmacodynamics. 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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\u2010positive African children, consisting of 19\u2009742 observations with weight ranging from 3.8 to 79.7\u00a0kg, height from 55.5 to 180\u00a0cm, and an age between 0.40 and 18\u00a0years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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\u2010to\u2010use paediatric population.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14694","type":"journal-article","created":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T05:56:36Z","timestamp":1607579796000},"page":"2847-2854","source":"Crossref","is-referenced-by-count":26,"title":["Constructing a representative in\u2010silico population for paediatric simulations: Application to HIV\u2010positive African children"],"prefix":"10.1111","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5769-8150","authenticated-orcid":false,"given":"Roeland E.","family":"Wasmann","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine University of Cape Town  Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0093-6445","authenticated-orcid":false,"given":"Elin M.","family":"Svensson","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences Uppsala University  Uppsala Sweden"},{"name":"Department of Pharmacy, Radboud Institute for Health Sciences Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0412-8509","authenticated-orcid":false,"given":"A. Sarah","family":"Walker","sequence":"additional","affiliation":[{"name":"MRC Clinical Trials Unit at UCL  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3442-3947","authenticated-orcid":false,"given":"Michelle N.","family":"Clements","sequence":"additional","affiliation":[{"name":"MRC Clinical Trials Unit at UCL  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7494-079X","authenticated-orcid":false,"given":"Paolo","family":"Denti","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Department of Medicine University of Cape Town  Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-015-1699-x"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200544100-00004"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-015-0277-z"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.48.113006.094708"},{"key":"e_1_2_10_6_1","first-page":"1","volume-title":"WHO Child Growth Standards Length\/Height\u2010for\u2010Age, Weight\u2010for\u2010Age, Weight\u2010for\u2010Length, Weight\u2010for\u2010Height and Body Mass Index\u2010for\u2010Age: Methods and Development","author":"World Health Organization","year":"2006"},{"issue":"246","key":"e_1_2_10_7_1","first-page":"1","article-title":"2000 CDC growth charts for the United States: methods and development","volume":"11","author":"Kuczmarski RJ","year":"2002","journal-title":"Vital Health Stat 11"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3156.2010.02634.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-017-0577-6"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)62198-9"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)00319-9"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2013.24"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/15648265040251S103"},{"key":"e_1_2_10_14_1","volume-title":"Prevalence of Obesity Among Adults and Youth: United States, 2015\u20102016. 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