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

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.	蔣建東. 我國兒童藥品研發與臨床用藥安全展望. 中國藥物警戒, 2023, 20(1): 1-6.
6.	王璐, 黃哲. 真實世界證據改善兒童藥物臨床試驗障礙的對策研究. 中國新藥雜志, 2022, 31(19): 1872-1875.
7.	趙瓊姝, 梁頔, 趙博, 等. 關于藥物臨床試驗兒童受試者知情同意問題的思考與建議. 中國醫學倫理學, 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.	吳娟, 張順國, 黃詩穎, 等. 兒童藥物臨床試驗的發展及現狀. 醫藥導報, 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.	國家食品藥品監督管理局. 《藥物臨床試驗質量管理規范》(局令第3號). 2003.
18.	國家食品藥品監督管理局. 疫苗臨床試驗技術指導原則. 2004.
19.	國務院婦女兒童工作委員會. 中國兒童發展綱要(2011-2020年). 2017.
20.	趙巖松, 洪蘭, 葉樺. 加快我國兒童用藥研發的政策與法規分析. 中國藥事, 2017, 31(1): 1-6.
21.	國家衛生計生委. 關于保障兒童用藥的若干意見. 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.	衛健委印發《國際疾病分類第十一次修訂本(ICD-11)中文版》. 醫學信息學雜志, 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.	許淑紅, 張綺, 張林琦, 等. 探討我國兒科用藥的發展現狀及政策層面的思考. 中國臨床藥理學雜志, 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年臨沂市6歲以下兒童免疫規劃疫苗接種預防效果調查. 中國校醫, 2021, 35(12): 906-908.
33.	倪韶青, 沈佳佳, 汪君依, 等. 中國注冊兒科藥物和疫苗臨床試驗開展現狀調查. 中華兒科雜志, 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.	Vrlji?ak Davidovi? N, Komi? L, Me?in 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. 蔣建東. 我國兒童藥品研發與臨床用藥安全展望. 中國藥物警戒, 2023, 20(1): 1-6.
6. 王璐, 黃哲. 真實世界證據改善兒童藥物臨床試驗障礙的對策研究. 中國新藥雜志, 2022, 31(19): 1872-1875.
7. 趙瓊姝, 梁頔, 趙博, 等. 關于藥物臨床試驗兒童受試者知情同意問題的思考與建議. 中國醫學倫理學, 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. 吳娟, 張順國, 黃詩穎, 等. 兒童藥物臨床試驗的發展及現狀. 醫藥導報, 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. 國家食品藥品監督管理局. 《藥物臨床試驗質量管理規范》(局令第3號). 2003.
18. 國家食品藥品監督管理局. 疫苗臨床試驗技術指導原則. 2004.
19. 國務院婦女兒童工作委員會. 中國兒童發展綱要(2011-2020年). 2017.
20. 趙巖松, 洪蘭, 葉樺. 加快我國兒童用藥研發的政策與法規分析. 中國藥事, 2017, 31(1): 1-6.
21. 國家衛生計生委. 關于保障兒童用藥的若干意見. 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. 衛健委印發《國際疾病分類第十一次修訂本(ICD-11)中文版》. 醫學信息學雜志, 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. 許淑紅, 張綺, 張林琦, 等. 探討我國兒科用藥的發展現狀及政策層面的思考. 中國臨床藥理學雜志, 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年臨沂市6歲以下兒童免疫規劃疫苗接種預防效果調查. 中國校醫, 2021, 35(12): 906-908.
33. 倪韶青, 沈佳佳, 汪君依, 等. 中國注冊兒科藥物和疫苗臨床試驗開展現狀調查. 中華兒科雜志, 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. Vrlji?ak Davidovi? N, Komi? L, Me?in 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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