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Off-label use of drugs in pediatrics: a scoping review

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Abstract

To explore the current state of research on off-label drug use in children and identify the existing research gaps in this topic. Six literature databases were searched to identify studies focusing exclusively on off-label drug use in children (aged < 18 years) published in Chinese or English between 2016 and 2021. We also searched clinicaltrials.gov for pediatric clinical trials conducted in the same period and compared the numbers of studies on off-label use and clinical trials for the most commonly reported drugs and drug types. Our search revealed 568 studies on off-label drug use. Almost half of the studies (n = 240) were cross-sectional. A total of 212 specific drugs or drug types were addressed in 361 studies, the most frequent being antipsychotic agents (n = 12), dexmedetomidine (n = 10), and rituximab (n = 8). Antipsychotic agents were also the most common type of drug examined in clinical trials in children. We identified a total of 435 different types of off-label use, the top three being unapproved indication (n = 157), population (n = 96), or age (n = 36). Only about one-third of the studies reported collecting informed consent (n = 195) or having ethics committee approval (n = 166).

   Conclusions: Off-label use of antipsychotics in children is widely reported in the literature. We suggest pediatric researchers to consider the number of studies on off-label use and existing clinical trials on different drugs when selecting target drugs for new studies and systematic reviews.

What is Known:

• There exist a large number of studies on off-label drug use in children.

What is New:

• This is the first scoping review of studies on off-label drug use in children.

• Off-label use of antipsychotic agents is widely reported.

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Abbreviations

CBM:

China Biology Medicine

CNKI:

China National Knowledge Infrastructure

FDA:

US Food and Drug Administration

PRISMA-ScR:

Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews

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Acknowledgements

We acknowledge Janne Estill, PhD (University of Geneva), for his assistance in writing the article.

Funding

All phases of this study were supported by Chongqing “Bayu Scholar” program.

Author information

Authors and Affiliations

  1. Chevidence Lab Child & Adolescent Health Department, Children’s Hospital of Chongqing Medical University, 136 Zhongshan Second Street, Chongqing, 400014, China

    Min Meng, Meng Lv, Bo Yang, Ruobing Lei, Tianchun Hou & Yaolong Chen

  2. National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, China

    Min Meng, Meng Lv, Bo Yang, Quan Shen, Ruobing Lei, Tianchun Hou, Yaolong Chen & Qiu Li

  3. Chongqing Key Laboratory of Pediatrics, Chongqing, 400014, China

    Min Meng, Meng Lv, Bo Yang, Quan Shen, Ruobing Lei, Tianchun Hou, Yaolong Chen & Qiu Li

  4. Department of Pharmacy, Gansu Provincial Hospital, Lanzhou, 730000, China

    Min Meng & Wenjuan Lei

  5. School of Public Health, Lanzhou University, Lanzhou, 730000, China

    Ling Wang, Hui Lan & Xufei Luo

  6. The First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China

    Panpan Jiao

  7. Lanzhou University Institute of Health Data Science, Lanzhou, 730000, China

    Qi Zhou, Xuan Yu, Yangqin Xun & Yaolong Chen

  8. Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 73000, China

    Qi Zhou, Xuan Yu, Yangqin Xun & Yaolong Chen

  9. WHO Collaborating Centre for Guideline Implementation and Knowledge Translation, Lanzhou, 73000, China

    Yaolong Chen

  10. Lanzhou University GRADE Center, Lanzhou, 73000, China

    Yaolong Chen

  11. Department of Nephrology, Children’s Hospital of Chongqing Medical University, 136 Zhongshan Second Street, Chongqing, China

    Qiu Li

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  1. Min Meng
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  2. Meng Lv
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  3. Ling Wang
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  15. Yaolong Chen
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  16. Qiu Li
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Contributions

Dr. Yaolong Chen and Dr. Qiu Li conceptualized and designed the study, analyzed and interpreted data, and reviewed and revised the manuscript critically. Min Meng and Ling Wang designed the data collection instruments, collected, interpreted, and analyzed data, and drafted the initial manuscript. Meng Lv and Yangqin Xun made charts and graphs, carried out the initial analyses, and reviewed and revised the manuscript. Ling Wang and Xuan Yu collected, analyzed and interpreted data, and drafted the initial manuscript. Xufei Luo and Qi Zhou conceptualized and designed the study, interpreted data, and critically reviewed the manuscript for important intellectual content. Bo Yang, Panpan Jao, Wenjuan Lei, and Hui Lan collected data, interpreted of data, and revised the article critically for important intellectual content. Quan Shen, Ruobing Lei, and Tianchun Hou optimized the data collection instruments, coordinated and supervised data collection, and revised the manuscript completely. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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Correspondence to Yaolong Chen or Qiu Li.

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Meng, M., Lv, M., Wang, L. et al. Off-label use of drugs in pediatrics: a scoping review. Eur J Pediatr 181, 3259–3269 (2022). https://doi.org/10.1007/s00431-022-04515-7

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