Analysis of registered industry-sponsored clinical trials of pediatric drugs in China_Chinese Journal of Evidence-Based Medicine

Authors：

JIANG Qijing ¹ , ZHAO Enhui ¹ , LU Zhenzhen ^2,3 , LI Bingzhe ^2,3 ,  HUANG Lihong ^2,3

1. School of Public Health, Fudan University, Shanghai 200032, P. R. China;
2. Department of Biostatistics, Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. China;
3. Clinical Research Center, Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. China;

Corresponding author：

HUANG Lihong, Email: huang.lihong@zs-hospital.sh.cn

Keywords：

Pediatrics; Drug industry; Clinical research; Registration characteristics; Policy

DOI：

10.7507/1672-2531.202303197

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To review the characteristics of registered industry-sponsored clinical trials of pediatric drugs and vaccines in China and to provide references for promoting the development of new pediatric drugs. Methods We searched ClinicalTrials.gov and the Chinese Clinical Trial Registry for completed registered industry-sponsored clinical trials of pediatric drugs and vaccines from the database inception to September 11, 2022. Data including the date the trial was first posted, product type (drug or vaccine), sample size, and other information to describe the general characteristics of pediatric clinical trials were collected. The studies were divided into 2 phases based on the trial posted date, 2005―2010 and 2011―2022, reflecting the enactment of pediatric drug clinical trial policies in recent years. The quality of trial registration and the main characteristics of interventional trials in the 2 phases were then compared. Exploring the results attached to industry and non-industry sponsored clinical trials. Results Data for 145 trials were collected, and the largest proportion (63.4%) involved vaccines. Randomized control trial (RCT) was the study type with the highest percentage (68.3%). The average report completion rate for registered interventional trials was 81.0%. Compared with 2005―2010, the percentage of average report completions, pediatric drug clinical studies, multicenter, RCTs, and double-blinded registered trials increased in 2011―2022. The proportion of positive outcomes in pediatric clinical trials sponsored by industries was higher than those sponsored by non-industry. Conclusion The majority of completed pediatric clinical trials sponsored by industries are for vaccines, in line with the promotion of pediatric policies. The quality of trial registration has improved, but not significantly, and some characteristics of trial design have changed. The proportion of positive outcomes in pediatric clinical trials sponsored by industries is higher. And further promotion of pediatric clinical trials is needed.

Citation： JIANG Qijing, ZHAO Enhui, LU Zhenzhen, LI Bingzhe, HUANG Lihong. Analysis of registered industry-sponsored clinical trials of pediatric drugs in China. Chinese Journal of Evidence-Based Medicine, 2023, 23(10): 1172-1180. doi: 10.7507/1672-2531.202303197 Copy

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2.	Balan S, Hassali MAA, Mak VSL. Two decades of off-label prescribing in children: a literature review. World J Pediatr, 2018, 14(6): 528-540.
3.	Mackall CL. In search of targeted therapies for childhood cancer. Front Oncol, 2011, 1(1): 18.
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8.	Cohen E, Uleryk E, Jasuja M, et al. An absence of pediatric randomized controlled trials in general medical journals, 1985-2004. J Clin Epidemiol, 2007, 60(2): 118-123.
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12.	Penkov D, Tomasi P, Eichler I, et al. Pediatric medicine development: an overview and comparison of regulatory processes in the European Union and United States. Ther Innov Regul Sci, 2017, 51(3): 360-371.
13.	Severin T, Corriol-Rohou S, Bucci-Rechtweg C, et al. How is the pharmaceutical industry structured to optimize pediatric drug development? Existing pediatric structure models and proposed recommendations for structural enhancement. Ther Innov Regul Sci, 2020, 54(5): 1076-1084.
14.	Shirkey H. Therapeutic orphans. J Pediatr, 1968, 72(1): 119-120.
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22.	Hao GX, Yuan XX, Guo W, et al. Paediatric drugs trials in China. BMJ Paediatr Open, 2020, 4(1): e000618.
23.	Calvert M, Kyte D, Mercieca-Bebber R, et al. Guidelines for inclusion of patient-reported outcomes in clinical trial protocols: the SPIRIT-PRO extension. JAMA, 2018, 319(5): 483-494.
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25.	卫健委印发《国际疾病分类第十一次修订本(ICD-11)中文版》. 医学信息学杂志, 2019, 40(2): 95.
26.	E11(R1) I G. Addendum to ICH E11: clinical investigation of medicinal products in the pediatric population, 2017-08-18.
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29.	Arnadottir J, Luc F, Kaguelidou F, et al. Analysis of paediatric clinical trial characteristics and activity over 23 years-impact of the european paediatric regulation on a single french clinical research center. Front Pediatr, 2022, 10(10): 842480.
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31.	Song L, Jia Y, Ran S, et al. Current situation of pediatric clinical trials in China: focus on trials for drug marketing application and administrative approval. BMC Pediatr, 2022, 22(1): 144.
32.	王黎明. 2016−2020年临沂市6岁以下儿童免疫规划疫苗接种预防效果调查. 中国校医, 2021, 35(12): 906-908.
33.	倪韶青, 沈佳佳, 汪君依, 等. 中国注册儿科药物和疫苗临床试验开展现状调查. 中华儿科杂志, 2021, 59(4): 299-304.
34.	Munsch MA, Chen SR, Dalton J, et al. Association between industry sponsorship of spine-related clinical trials, publication status, and research outcomes. Global Spine J, 2023, 21925682231166379.
35.	Vrljičak Davidović N, Komić L, Mešin I, et al. Registry versus publication: discrepancy of primary outcomes and possible outcome reporting bias in child and adolescent mental health. Eur Child Adolesc Psychiatry, 2022, 31(5): 757-769.
36.	Pyke S, Julious SA, Day S, et al. The potential for bias in reporting of industry-sponsored clinical trials. Pharm Stat, 2011, 10(1): 74-79.
37.	Onishi T, Tsukamoto K, Matsumaru N, et al. Industry perspective of pediatric drug development in the United States: involvement of the european union countries. Ther Innov Regul Sci, 2018, 52(1): 49-56.
38.	El Zoghbi S, Jannot A, Delacourt C, et al. French pediatricians' views on industry-sponsored clinical trials: Toward stronger research on ethics? Arch Pediatr, 2021, 28(6): 459-463.

1. Lagler FB, Hirschfeld S, Kindblom JM. Challenges in clinical trials for children and young people. Arch Dis Child, 2021, 106(4): 321-325.
2. Balan S, Hassali MAA, Mak VSL. Two decades of off-label prescribing in children: a literature review. World J Pediatr, 2018, 14(6): 528-540.
3. Mackall CL. In search of targeted therapies for childhood cancer. Front Oncol, 2011, 1(1): 18.
4. Roberts R, Rodriguez W, Murphy D, et al. Pediatric drug labeling: improving the safety and efficacy of pediatric therapies. JAMA, 2003, 290(7): 905-911.
5. 蒋建东. 我国儿童药品研发与临床用药安全展望. 中国药物警戒, 2023, 20(1): 1-6.
6. 王璐, 黄哲. 真实世界证据改善儿童药物临床试验障碍的对策研究. 中国新药杂志, 2022, 31(19): 1872-1875.
7. 赵琼姝, 梁頔, 赵博, 等. 关于药物临床试验儿童受试者知情同意问题的思考与建议. 中国医学伦理学, 2019, 32(10): 1247-1252.
8. Cohen E, Uleryk E, Jasuja M, et al. An absence of pediatric randomized controlled trials in general medical journals, 1985-2004. J Clin Epidemiol, 2007, 60(2): 118-123.
9. Gans-Brangs KR, Plourde PV. The evolution of legislation to regulate pediatric clinical trials: Present and continuing challenges. Adv Drug Deliv Rev, 2006, 58(1): 106-115.
10. Neubert A, Planner C, Cranswick N. The new European regulation on pediatric medicines: safety and ethics perspectives. Paediatr Drugs, 2008, 10(3): 147-149.
11. 吴娟, 张顺国, 黄诗颖, 等. 儿童药物临床试验的发展及现状. 医药导报, 2018, 37(1): 74-77.
12. Penkov D, Tomasi P, Eichler I, et al. Pediatric medicine development: an overview and comparison of regulatory processes in the European Union and United States. Ther Innov Regul Sci, 2017, 51(3): 360-371.
13. Severin T, Corriol-Rohou S, Bucci-Rechtweg C, et al. How is the pharmaceutical industry structured to optimize pediatric drug development? Existing pediatric structure models and proposed recommendations for structural enhancement. Ther Innov Regul Sci, 2020, 54(5): 1076-1084.
14. Shirkey H. Therapeutic orphans. J Pediatr, 1968, 72(1): 119-120.
15. Wilson JT. An update on the therapeutic orphan. Pediatrics, 1999, 104(3): 585-590.
16. Ward RM, Benjamin DK, Davis JM, et al. The need for pediatric drug development. J Pediatr, 2018, 192: 13-21.
17. 国家食品药品监督管理局. 《药物临床试验质量管理规范》(局令第3号). 2003.
18. 国家食品药品监督管理局. 疫苗临床试验技术指导原则. 2004.
19. 国务院妇女儿童工作委员会. 中国儿童发展纲要(2011-2020年). 2017.
20. 赵岩松, 洪兰, 叶桦. 加快我国儿童用药研发的政策与法规分析. 中国药事, 2017, 31(1): 1-6.
21. 国家卫生计生委. 关于保障儿童用药的若干意见. 2014.
22. Hao GX, Yuan XX, Guo W, et al. Paediatric drugs trials in China. BMJ Paediatr Open, 2020, 4(1): e000618.
23. Calvert M, Kyte D, Mercieca-Bebber R, et al. Guidelines for inclusion of patient-reported outcomes in clinical trial protocols: the SPIRIT-PRO extension. JAMA, 2018, 319(5): 483-494.
24. Mehran R, Baber U, Dangas G. Guidelines for patient-reported outcomes in clinical trial protocols. JAMA, 2018, 319(5): 450-451.
25. 卫健委印发《国际疾病分类第十一次修订本(ICD-11)中文版》. 医学信息学杂志, 2019, 40(2): 95.
26. E11(R1) I G. Addendum to ICH E11: clinical investigation of medicinal products in the pediatric population, 2017-08-18.
27. 许淑红, 张绮, 张林琦, 等. 探讨我国儿科用药的发展现状及政策层面的思考. 中国临床药理学杂志, 2020, 36(12): 1760-1767.
28. World Health Organization. WHO trial registration data set (version 1.3. 1).
29. Arnadottir J, Luc F, Kaguelidou F, et al. Analysis of paediatric clinical trial characteristics and activity over 23 years-impact of the european paediatric regulation on a single french clinical research center. Front Pediatr, 2022, 10(10): 842480.
30. Wu WW, Ji X, Wang H, et al. Pediatric clinical trials in mainland china over the past decade (from 2009 to 2020). Front Med (Lausanne), 2021, 8: 745676.
31. Song L, Jia Y, Ran S, et al. Current situation of pediatric clinical trials in China: focus on trials for drug marketing application and administrative approval. BMC Pediatr, 2022, 22(1): 144.
32. 王黎明. 2016−2020年临沂市6岁以下儿童免疫规划疫苗接种预防效果调查. 中国校医, 2021, 35(12): 906-908.
33. 倪韶青, 沈佳佳, 汪君依, 等. 中国注册儿科药物和疫苗临床试验开展现状调查. 中华儿科杂志, 2021, 59(4): 299-304.
34. Munsch MA, Chen SR, Dalton J, et al. Association between industry sponsorship of spine-related clinical trials, publication status, and research outcomes. Global Spine J, 2023, 21925682231166379.
35. Vrljičak Davidović N, Komić L, Mešin I, et al. Registry versus publication: discrepancy of primary outcomes and possible outcome reporting bias in child and adolescent mental health. Eur Child Adolesc Psychiatry, 2022, 31(5): 757-769.
36. Pyke S, Julious SA, Day S, et al. The potential for bias in reporting of industry-sponsored clinical trials. Pharm Stat, 2011, 10(1): 74-79.
37. Onishi T, Tsukamoto K, Matsumaru N, et al. Industry perspective of pediatric drug development in the United States: involvement of the european union countries. Ther Innov Regul Sci, 2018, 52(1): 49-56.
38. El Zoghbi S, Jannot A, Delacourt C, et al. French pediatricians' views on industry-sponsored clinical trials: Toward stronger research on ethics? Arch Pediatr, 2021, 28(6): 459-463.

Chinese Journal of Evidence-Based Medicine

Analysis of registered industry-sponsored clinical trials of pediatric drugs in China

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