{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:16:34Z","timestamp":1790255794325,"version":"4.1.0"},"reference-count":126,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T00:00:00Z","timestamp":1771113600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T00:00:00Z","timestamp":1771113600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Despite regulatory progress being made in the past two decades, off\u2010label drug use in paediatrics remains pervasive, with prevalence estimated between 3% and 97% of prescriptions across different clinical settings. Off\u2010label use\u2014defined as prescribing outside the conditions described in the Summary of Product Characteristics (SmPC)\u2014is often unavoidable due to the lack of authorized paediatric indications, particularly for older, off\u2010patent drugs. The level of evidence for off\u2010label use is strikingly low: strong evidence supports only 14% of off\u2010label paediatric drug records, while 37% of dosing recommendations rely solely on expert consensus. This practice exposes children to increased risks of adverse drug reactions (OR 2.25; 95% CI 1.95\u20132.59) and dosing errors, driven by insufficient evidence on age\u2010appropriate dosing, efficacy and safety. Children remain \u2018therapeutic orphans\u2019, and the true challenge lies not in the absence of marketing authorization, but in the persistent evidence gap.<\/jats:p>\n                  <jats:p>\n                    This narrative review examines strategies to mitigate risks associated with paediatric off\u2010label drug use proposing a five\u2010step framework\n                    <jats:sup>1<\/jats:sup>\n                    : verify authorization status\n                    <jats:sup>2<\/jats:sup>\n                    ; confirm unmet medical need\n                    <jats:sup>3<\/jats:sup>\n                    ; assess benefit\u2013risk balance using structured published tools\n                    <jats:sup>4<\/jats:sup>\n                    ensure proportional informed consent and\n                    <jats:sup>5<\/jats:sup>\n                    closing the knowledge gap.\n                  <\/jats:p>\n                  <jats:p>Closing knowledge gaps through research prioritization, evidence mapping and innovative methodologies such as paediatric extrapolation, modelling and simulation, real\u2010world evidence use and innovative trial designs will enable safer, scientifically grounded off\u2010label use. Dissemination via harmonized international paediatric drug information platforms is critical to ensure equitable access to best\u2010evidence paediatric pharmacotherapy.<\/jats:p>\n                  <jats:p>Off\u2010label use in paediatrics is a global reality demanding a paradigm shift from \u2018off\u2010label\u2019 to \u2018on\u2010evidence\u2019.<\/jats:p>","DOI":"10.1002\/bcp.70461","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T06:30:58Z","timestamp":1771223458000},"source":"Crossref","is-referenced-by-count":2,"title":["Beyond the label: Rethinking off\u2010label drug use in paediatrics. Towards a scientifically grounded and safer future for paediatric pharmacotherapy"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1201-0591","authenticated-orcid":false,"given":"Tjitske M.","family":"van der Zanden","sequence":"first","affiliation":[{"name":"Paediatric and neonatal Intensive Care, Erasmus MC Sophia Children's Hospital Rotterdam  The Netherlands"},{"name":"Departments of Pharmacy, Pharmacology and Toxicology, Radboud University Medical Centre Nijmegen  The Netherlands"},{"name":"Dutch Knowledge Centre Pharmacotherapy for Children  The Hague The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam G.","family":"Mooij","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, division of Paediatric Nephrology, Erasmus MC \u2010 Sophia Children's Hospital Rotterdam  The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthijs","family":"de 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