Meng Min, Zhou Qi, Lei Wenjuan, Tian Min, Wang Ping, Liu Yunlan, Sun Yajia, Chen Yaolong, Li Qiu
Department of Chevidence Lab Child & Adolescent Health, Children's Hospital of Chongqing Medical University, Chongqing, China.
Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
Front Pharmacol. 2022 Jun 9;13:892574. doi: 10.3389/fphar.2022.892574. eCollection 2022.
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. A cross-sectional study was performed by systematic search through MEDLINE ( 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. 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 ( = 314, 14.0%), pediatric case series studies ( = 260, 11.6%), and reviews ( = 255, 11.4%). Twenty-one percent ( = 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 ( = 255, 48.8%). Sixty-nine (11.4%) recommendations explicitly reported the drug use as off-label. Children may be exposed to medical risks due to gaps in reporting and evidence of off-label drug use recommendations in pediatric guidelines.
系统分析儿科指南中关于药品未按说明书用药建议的支持证据、药物信息及未按说明书用药的类型。通过系统检索MEDLINE（PubMed）和Embase数据库进行横断面研究，以识别2018年1月1日至2020年12月31日发表的文献。仅纳入包含药品未按说明书用药建议的儿科临床实践指南。我们呈现了关于纳入指南的来源、国家、出版年份、使用的证据分级系统、未按说明书用药类型的详细信息，以及用作支持建议的研究类型的描述性信息。共纳入66部儿科指南及605条建议。87条（14.4%）建议未引用任何参考文献；其余518条建议得到2240篇参考文献的支持（平均每条建议4.3篇参考文献）。引用最多的研究类型是儿科随机对照试验（n = 314，14.0%）、儿科病例系列研究（n = 260，11.6%）和综述（n = 255，11.4%）。21%（n = 470）的参考文献是关于成人的研究。140条（23.1%）建议使用推荐分级、评估、制定与评价（GRADE）系统进行分级，其中37条（26.4%）被评为强推荐，但仅得到C级或D级证据的支持。建议中最常报告的信息类型是适应证（n = 499，82.5%）。523条肯定性建议中最常涉及的未按说明书用药类型是未获批人群（n = 255，48.8%）。69条（11.4%）建议明确将药物使用报告为未按说明书用药。由于儿科指南中未按说明书用药建议的报告和证据存在差距，儿童可能面临医疗风险。
