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. 2022 Jun 9:13:892574.
doi: 10.3389/fphar.2022.892574. eCollection 2022.

Recommendations on Off-Label Drug Use in Pediatric Guidelines

Min Meng  1   2   3   4 , Qi Zhou  5   6 , Wenjuan Lei  4 , Min Tian  4 , Ping Wang  5   6 , Yunlan Liu  7 , Yajia Sun  7 , Yaolong Chen  1   2   3   5   6   7   8   9   10 , Qiu Li  2   3   11
Affiliations

Recommendations on Off-Label Drug Use in Pediatric Guidelines

Min Meng et al. Front Pharmacol. .

Abstract

Objective: 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. Methods: A cross-sectional study was performed by systematic search through MEDLINE (via 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. Results: 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 (n = 314, 14.0%), pediatric case series studies (n = 260, 11.6%), and reviews (n = 255, 11.4%). Twenty-one percent (n = 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 (n = 255, 48.8%). Sixty-nine (11.4%) recommendations explicitly reported the drug use as off-label. Conclusion: Children may be exposed to medical risks due to gaps in reporting and evidence of off-label drug use recommendations in pediatric guidelines.

Keywords: children; evidence-based medicine; off-label use of drugs; pediatric guidelines; recommendations.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Guideline screening process.
FIGURE 2
FIGURE 2
The types of references cited to support the recommendations.
FIGURE 3
FIGURE 3
Strength of the off-label drug use recommendations and quality of the supporting evidence according to the GRADE grading system.
See this image and copyright information in PMC

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