AUTHOR=Meng Min , Zhou Qi , Lei Wenjuan , Tian Min , Wang Ping , Liu Yunlan , Sun Yajia , Chen Yaolong , Li Qiu 

TITLE=Recommendations on Off-Label Drug Use in Pediatric Guidelines

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.892574

DOI=10.3389/fphar.2022.892574

ISSN=1663-9812

ABSTRACT=<p><bold>Objective:</bold> To systematically analyze the supporting evidence, drug information, and the type of off-label drug use in recommendations on off-label drug use in pediatric guidelines.</p><p><bold>Methods:</bold> A cross-sectional study was performed by systematic search through MEDLINE (<italic>via</italic> PubMed) and Embase databases to identify literature published from 1 January 2018, to 31 December 2020. Only pediatric clinical practice guidelines that included recommendations on off-label use of drugs were included. We present descriptive information on the sources of the included guidelines, country, publication year, evidence grading system used, details on the types of off-label drug use, and the types of studies used as references to support the recommendations.</p><p><bold>Results:</bold> A total of 66 pediatric guidelines with 605 recommendations were included. Eighty-seven (14.4%) recommendations did not cite any references; and the remaining 518 recommendations were supported by 2,240 references (mean 4.3 references/recommendation). The most common types of studies cited were pediatric RCTs (<italic>n</italic> = 314, 14.0%), pediatric case series studies (<italic>n</italic> = 260, 11.6%), and reviews (<italic>n</italic> = 255, 11.4%). Twenty-one percent (<italic>n</italic> = 470) of the references were studies on adults. One hundred and forty (23.1%) recommendations were graded using the Grading of Recommendations, Assessments, Development, and Evaluations (GRADE) system, of which 37 (26.4%) were graded as strong but supported with only C or D level of evidence. The most commonly reported type of information in the recommendations was indication (n = 499, 82.5%). The most commonly addressed type of off-label drug use in the 523 positive recommendations was unapproved population (<italic>n</italic> = 255, 48.8%). Sixty-nine (11.4%) recommendations explicitly reported the drug use as off-label.</p><p><bold>Conclusion:</bold> Children may be exposed to medical risks due to gaps in reporting and evidence of off-label drug use recommendations in pediatric guidelines.</p>