{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T08:32:07Z","timestamp":1767947527632,"version":"3.49.0"},"reference-count":11,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study investigates the formal definitions of \u201coff-label\u201d medication use among five major Western regulatory authorities\u2014FDA, EMA, Health Canada, MHRA, and TGA. The primary research question is whether these agencies provide explicit, official definitions of off-label use.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>The study employs a mixed-methods design, combining direct inquiries via standardized questionnaires with AI-assisted text mining of publicly available regulatory documents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Regulatory agencies at a national level across North America, Europe, and Oceania.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>Five agencies, with data collected through direct contact and automated document analysis; no human participants were involved.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Intervention<\/jats:title>\n                    <jats:p>Analysing agency webpages and documents for sentences that resemble formal definitions, followed by manual review and categorization based on linguistic and contextual criteria.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main outcome<\/jats:title>\n                    <jats:p>The presence or absence of official definitions, the content and clarity of any definitional statements, and their prominence within regulatory documents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>None of the agencies provide a formal, official definition of off-label use. However, all agencies\u2019 publicly available documents contain statements that resemble definitions, generally describing off-label use as prescribing beyond the conditions approved by the drug\u2019s marketing authorization. Despite similarities in language, the clarity and prominence of these statements vary across agencies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The lack of formal off-label definitions may contribute to legal ambiguity, clinical uncertainty, and challenges in guideline development, particularly affecting paediatric populations where off-label prescribing is common. The regulatory agencies should adopt clear, standardized official definitions of off-label use to improve transparency, legal coherence, and patient safety.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1750718","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T06:36:09Z","timestamp":1767940569000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Lack of formal regulatory definitions of off-label medication use in children: an analysis using agency inquiry and text mining"],"prefix":"10.3389","volume":"16","author":[{"given":"Christina","family":"Gade","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrik","family":"Lausten-Thomsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1111\/bcp.12750","article-title":"Awareness, knowledge and views of off-label prescribing in children: a systematic review","volume":"80","author":"Balan","year":"2015","journal-title":"Br. 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