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Off‐Label, but on‐Evidence? A Review of the Level of Evidence for Pediatric Pharmacotherapy
Many drugs are still prescribed off‐label to the pediatric population. Although off‐label drug use not supported by high level of evidence is potentially harmful, a comprehensive overview of the quality of the evidence pertaining off‐label drug use in children is lacking. The Dutch Pediatric Formula...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9828396/ https://www.ncbi.nlm.nih.gov/pubmed/36069288 http://dx.doi.org/10.1002/cpt.2736 |
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author | van der Zanden, Tjitske M. Smeets, Nori J.L. de Hoop‐Sommen, Marika Schwerzel, Michiel F.T. Huang, Hui Jun Barten, Lieke J.C. van der Heijden, Joyce E.M. Freriksen, Jolien J.M. Horstink, Akira A.L. Holsappel, Inge H.G. Mooij, Miriam G. de Hoog, Matthijs de Wildt, Saskia N. |
author_facet | van der Zanden, Tjitske M. Smeets, Nori J.L. de Hoop‐Sommen, Marika Schwerzel, Michiel F.T. Huang, Hui Jun Barten, Lieke J.C. van der Heijden, Joyce E.M. Freriksen, Jolien J.M. Horstink, Akira A.L. Holsappel, Inge H.G. Mooij, Miriam G. de Hoog, Matthijs de Wildt, Saskia N. |
author_sort | van der Zanden, Tjitske M. |
collection | PubMed |
description | Many drugs are still prescribed off‐label to the pediatric population. Although off‐label drug use not supported by high level of evidence is potentially harmful, a comprehensive overview of the quality of the evidence pertaining off‐label drug use in children is lacking. The Dutch Pediatric Formulary (DPF) provides best evidence‐based dosing guidelines for drugs used in children. For each drug‐indication‐age group combination—together compiling one record—we scored the highest available level of evidence: labeled use, systematic review or meta‐analysis, randomized controlled trial (RCT), comparative research, noncomparative research, or consensus‐based expert opinions. For records based on selected guidelines, the original sources were not reviewed. These records were scored as guideline. A total of 774 drugs were analyzed comprising a total of 6,426 records. Of all off‐label records (n = 2,718), 14% were supported by high quality evidence (4% meta‐analysis or systematic reviews, 10% RCTs of high quality), 20% by comparative research, 14% by noncomparative research, 37% by consensus‐based expert opinions, and 15% by selected guidelines. Fifty‐eight percent of all records were authorized, increasing with age from 30% in preterm neonates (n = 110) up to 64% in adolescents (n = 1,630). Many have advocated that off‐label use is only justified when supported by a high level of evidence. We show that this prerequisite would seriously limit available drug treatment for children as the underlying evidence is low across ages and drug classes. Our data identify the drugs and therapeutic areas for which evidence is clearly missing and could drive the global research agenda. |
format | Online Article Text |
id | pubmed-9828396 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98283962023-01-11 Off‐Label, but on‐Evidence? A Review of the Level of Evidence for Pediatric Pharmacotherapy van der Zanden, Tjitske M. Smeets, Nori J.L. de Hoop‐Sommen, Marika Schwerzel, Michiel F.T. Huang, Hui Jun Barten, Lieke J.C. van der Heijden, Joyce E.M. Freriksen, Jolien J.M. Horstink, Akira A.L. Holsappel, Inge H.G. Mooij, Miriam G. de Hoog, Matthijs de Wildt, Saskia N. Clin Pharmacol Ther Research Many drugs are still prescribed off‐label to the pediatric population. Although off‐label drug use not supported by high level of evidence is potentially harmful, a comprehensive overview of the quality of the evidence pertaining off‐label drug use in children is lacking. The Dutch Pediatric Formulary (DPF) provides best evidence‐based dosing guidelines for drugs used in children. For each drug‐indication‐age group combination—together compiling one record—we scored the highest available level of evidence: labeled use, systematic review or meta‐analysis, randomized controlled trial (RCT), comparative research, noncomparative research, or consensus‐based expert opinions. For records based on selected guidelines, the original sources were not reviewed. These records were scored as guideline. A total of 774 drugs were analyzed comprising a total of 6,426 records. Of all off‐label records (n = 2,718), 14% were supported by high quality evidence (4% meta‐analysis or systematic reviews, 10% RCTs of high quality), 20% by comparative research, 14% by noncomparative research, 37% by consensus‐based expert opinions, and 15% by selected guidelines. Fifty‐eight percent of all records were authorized, increasing with age from 30% in preterm neonates (n = 110) up to 64% in adolescents (n = 1,630). Many have advocated that off‐label use is only justified when supported by a high level of evidence. We show that this prerequisite would seriously limit available drug treatment for children as the underlying evidence is low across ages and drug classes. Our data identify the drugs and therapeutic areas for which evidence is clearly missing and could drive the global research agenda. John Wiley and Sons Inc. 2022-09-25 2022-12 /pmc/articles/PMC9828396/ /pubmed/36069288 http://dx.doi.org/10.1002/cpt.2736 Text en © 2022 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Research van der Zanden, Tjitske M. Smeets, Nori J.L. de Hoop‐Sommen, Marika Schwerzel, Michiel F.T. Huang, Hui Jun Barten, Lieke J.C. van der Heijden, Joyce E.M. Freriksen, Jolien J.M. Horstink, Akira A.L. Holsappel, Inge H.G. Mooij, Miriam G. de Hoog, Matthijs de Wildt, Saskia N. Off‐Label, but on‐Evidence? A Review of the Level of Evidence for Pediatric Pharmacotherapy |
title | Off‐Label, but on‐Evidence? A Review of the Level of Evidence for Pediatric Pharmacotherapy |
title_full | Off‐Label, but on‐Evidence? A Review of the Level of Evidence for Pediatric Pharmacotherapy |
title_fullStr | Off‐Label, but on‐Evidence? A Review of the Level of Evidence for Pediatric Pharmacotherapy |
title_full_unstemmed | Off‐Label, but on‐Evidence? A Review of the Level of Evidence for Pediatric Pharmacotherapy |
title_short | Off‐Label, but on‐Evidence? A Review of the Level of Evidence for Pediatric Pharmacotherapy |
title_sort | off‐label, but on‐evidence? a review of the level of evidence for pediatric pharmacotherapy |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9828396/ https://www.ncbi.nlm.nih.gov/pubmed/36069288 http://dx.doi.org/10.1002/cpt.2736 |
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