. 2022 Jul 23;22(1):442.

doi: 10.1186/s12887-022-03457-1.

Guideline for the management of pediatric off-label use of drugs in China (2021)

Min Meng^#^{1

2

3

4}, Enmei Liu^#^{1

2

3}, Bo Zhang⁵, Quan Lu⁶, Xiaobo Zhang⁷, Bin Ge⁴, Ye Wu⁸, Li Wang⁹, Mo Wang^{1

2

3}, Zhengxiu Luo^{1

2

3}, Ziyu Hua^{1

2

3}, Xiaoling Wang¹⁰, Wei Zhao¹¹, Yi Zheng¹¹, Xinan Wu¹², Ruiling Zhao¹³, Wenbo Meng¹², Li Xiang¹⁰, Gang Wang^{1

2

3}, Yuntao Jia^{1

2

3}, Yongchuan Chen¹⁴, Xiaoyan Dong⁶, Lina Hao¹⁵, Chengjun Liu^{1

2

3}, Meng Lv^{1

2

3}, Xufei Luo¹⁶, Yunlan Liu¹⁶, Quan Shen^{1

2

3}, Wenjuan Lei⁴, Ping Wang¹⁷, Yajia Sun¹⁷, Juanjuan Zhang¹⁶, Ling Wang¹⁶, Ruobing Lei^{1

2

3}, Tianchun Hou^{1

2

3}, Bo Yang^{1

2

3}, Qiu Li^{18

19

20}, Yaolong Chen^{21

22

23

24

25

26

27

28}

Affiliations

¹ Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
² National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
³ Chongqing Key Laboratory of Pediatrics, Chongqing, 400014, China.
⁴ Gansu Provincial Hospital, Lanzhou, 730000, China.
⁵ Department of Pharmacy, Peking Union Medical College Hospital, Beijing, 100730, China.
⁶ Department of Pulmonology, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200040, China.
⁷ Children's Hospital of Fudan University, Shanghai, 201102, China.
⁸ Peking University First Hospital, Beijing, 100034, China.
⁹ Peking University, Beijing, 100871, China.
¹⁰ Beijing Children's Hospital, Capital Medical University, Beijing, 100045, China.
¹¹ Shandong University, Jinan, 250100, China.
¹² The First Hospital of Lanzhou University, Lanzhou, 730000, China.
¹³ Children's Hospital of Shanxi, Taiyuan, 030012, China.
¹⁴ The First Affiliated Hospital of Third Military Medical University (Army Medical University), Chongqing, 400038, China.
¹⁵ Children's Hospital Affiliated to Shandong University, Jinan, 250022, China.
¹⁶ School of Public Health, Lanzhou University, Lanzhou, 730000, China.
¹⁷ Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China.
¹⁸ Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China. liqiu809@hospital.cqmu.edu.cn.
¹⁹ National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China. liqiu809@hospital.cqmu.edu.cn.
²⁰ Chongqing Key Laboratory of Pediatrics, Chongqing, 400014, China. liqiu809@hospital.cqmu.edu.cn.
²¹ Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China. chenyaolong@lzu.edu.cn.
²² National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China. chenyaolong@lzu.edu.cn.
²³ Chongqing Key Laboratory of Pediatrics, Chongqing, 400014, China. chenyaolong@lzu.edu.cn.
²⁴ Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China. chenyaolong@lzu.edu.cn.
²⁵ Research Unit of Evidence-Based Evaluation and Guidelines, Chinese Academy of Medical Sciences (2021RU017), School of Basic Medical Sciences, Lanzhou University, Lanzhou University Institute of Health Data Science, Lanzhou, 730000, China. chenyaolong@lzu.edu.cn.
²⁶ Lanzhou University Institute of Health Data Science, Lanzhou, 730000, China. chenyaolong@lzu.edu.cn.
²⁷ WHO Collaborating Centre for Guideline Implementation and Knowledge Translation, Lanzhou, 730000, China. chenyaolong@lzu.edu.cn.
²⁸ Lanzhou University GRADE Center, Lanzhou, 730000, China. chenyaolong@lzu.edu.cn.

^# Contributed equally.

PMID: 35869466
PMCID: PMC9307429
DOI: 10.1186/s12887-022-03457-1

Guideline for the management of pediatric off-label use of drugs in China (2021)

Min Meng et al. BMC Pediatr. 2022.

. 2022 Jul 23;22(1):442.

doi: 10.1186/s12887-022-03457-1.

Authors

Affiliations

¹ Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
² National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
³ Chongqing Key Laboratory of Pediatrics, Chongqing, 400014, China.
⁴ Gansu Provincial Hospital, Lanzhou, 730000, China.
⁵ Department of Pharmacy, Peking Union Medical College Hospital, Beijing, 100730, China.
⁶ Department of Pulmonology, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200040, China.
⁷ Children's Hospital of Fudan University, Shanghai, 201102, China.
⁸ Peking University First Hospital, Beijing, 100034, China.
⁹ Peking University, Beijing, 100871, China.
¹⁰ Beijing Children's Hospital, Capital Medical University, Beijing, 100045, China.
¹¹ Shandong University, Jinan, 250100, China.
¹² The First Hospital of Lanzhou University, Lanzhou, 730000, China.
¹³ Children's Hospital of Shanxi, Taiyuan, 030012, China.
¹⁴ The First Affiliated Hospital of Third Military Medical University (Army Medical University), Chongqing, 400038, China.
¹⁵ Children's Hospital Affiliated to Shandong University, Jinan, 250022, China.
¹⁶ School of Public Health, Lanzhou University, Lanzhou, 730000, China.
¹⁷ Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China.
¹⁸ Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China. liqiu809@hospital.cqmu.edu.cn.
¹⁹ National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China. liqiu809@hospital.cqmu.edu.cn.
²⁰ Chongqing Key Laboratory of Pediatrics, Chongqing, 400014, China. liqiu809@hospital.cqmu.edu.cn.
²¹ Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China. chenyaolong@lzu.edu.cn.
²² National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China. chenyaolong@lzu.edu.cn.
²³ Chongqing Key Laboratory of Pediatrics, Chongqing, 400014, China. chenyaolong@lzu.edu.cn.
²⁴ Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China. chenyaolong@lzu.edu.cn.
²⁵ Research Unit of Evidence-Based Evaluation and Guidelines, Chinese Academy of Medical Sciences (2021RU017), School of Basic Medical Sciences, Lanzhou University, Lanzhou University Institute of Health Data Science, Lanzhou, 730000, China. chenyaolong@lzu.edu.cn.
²⁶ Lanzhou University Institute of Health Data Science, Lanzhou, 730000, China. chenyaolong@lzu.edu.cn.
²⁷ WHO Collaborating Centre for Guideline Implementation and Knowledge Translation, Lanzhou, 730000, China. chenyaolong@lzu.edu.cn.
²⁸ Lanzhou University GRADE Center, Lanzhou, 730000, China. chenyaolong@lzu.edu.cn.

^# Contributed equally.

PMID: 35869466
PMCID: PMC9307429
DOI: 10.1186/s12887-022-03457-1

Abstract

Background: The "Law on Doctors of the People's Republic of China," which was officially implemented on March 1, 2022, emphasizes the requirements for rational drug use and the necessity for appropriate management of off-label drug use. The safety and ethical considerations related to off-label drug use are different in children than in adults. There is so far no management guideline for pediatric off-label use of drugs in China, and the applicability of foreign guidelines is limited. Establishing a localized evidence-based management guideline for pediatric off-label use of drugs to support the national legislation and clinical practice is of critical importance.

Methods: We established a guideline working group, including experts from a broad range of disciplines and developed recommendations following the guidance of the World Health Organization Handbook and the Chinese Medical Association. The following themes were identified by questionnaires and expert interviews to be of great concern in the management of off-label drug use in children: general principles and characteristics of management of pediatric off-label drug use; establishment of expert committees; evidence evaluation; risk-benefit assessment; informed consent; monitoring and assessment of the risk; and monitoring and patient education. Two rounds of Delphi surveys were organized to determine the final recommendations of this guideline. We graded the recommendations based on the body of evidence, referring to the evaluation tool of the Evidence-based management (EBMgt) and the Oxford Center for Evidence-Based Medicine: Level of Evidence (March 2009).

Results: We developed the first guideline for the management of pediatric off-label use of drugs in China.

Conclusions: The guideline is to offer guidance for pediatricians, pharmacists, medical managers, policymakers, and primary care physicians on how to manage off-label drug use in pediatrics and to provide recommendations for Chinese healthcare policy in the future.

Keywords: Children; Guideline; Management; Off-label use of drugs.

PubMed Disclaimer

Conflict of interest statement

The study/development of guidelines were approved by the Chinese Society of Pediatric Clinical Pharmacology, the Chinese Medical Association, the National Clinical Medical Research Center for Child Health and Disease (Children's Hospital of Chongqing Medical University), and the Chinese GRADE Center. Participation of all participants were voluntarily and they were informed about the objective of the study. All members completed a declaration of interest form and stated that they had no economic conflicts of interest directly relevant to this guideline. All methods were carried out in relevant regulations and guidelines.

The authors declare that they have no competing interests.

Figures

**Fig. 1**
Framework for benefit-risk assessment of pediatric off-label use of drugs

See this image and copyright information in PMC

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Guideline for the management of pediatric off-label use of drugs in China (2021)

Affiliations

Guideline for the management of pediatric off-label use of drugs in China (2021)

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Conflict of interest statement

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