Published: 2022-08-24

Clinical trials in pediatrics-review of ethics and law

Anitha P., Ruchi Dhar, Narayana Krishnappa


Children were acknowledged as ‘therapeutic or pharmaceutical orphans’ in 1960s, since then there has been a worldwide recognition of the need to conduct clinical trials in children, to improve their health. Prescribing in children is often based on extrapolation of trial results from adults, due to the lack of paediatric data. Children have different pharmacokinetic and pharmacodynamics responses as compared to adults. Hence extrapolating the adult safety and efficacy data and using it for prescribing in children can have disastrous effects. Relevant literature on clinical trials in paediatrics was gathered and scrutinized with emphasis on legal and ethical perspectives. This research is an exploratory attempt which surveys and summarizes previously published studies simultaneously trying to answer few research questions which addresses the current debates and scenario. Common problems encountered during pediatric clinical trials are unnecessary scrutiny of even minimal risk studies, difference in interpretation of research protocol in multicentre trials causing delay in trials, prolonged review process. The proposed changes to overcome the above mentioned drawbacks are standardized data security protections, enforcing universal ethical principles for conducting pediatric trials, sstandardizing adverse drug reaction reporting to regulatory bodies. There is a need to increase the number of clinicians actively involved in pediatric research. All the stake-holders such as regulators, parents, ethics committees, research institutions, investigators, sponsors, media, pharmaceutical companies and scientists have to collaborate to ensure that ethical pediatric research is promoted, equipping them with knowledge needed to provide optimal care to their patients.


Pediatric clinical trials, Law, Ethics

Full Text:



Thorat SB, Banarjee SK, Gaikwad DD, Jadhav SL, Thorat RM. Microencapsulation: a review. Int J Pharmaceutical Sci Rev Res. 2010;1(2).

Wilson JT. An update on the therapeutic orphan. Pediatrics. 1999;104(3):585-90.

Sammons H, Gray C, Hudson H, Cherrill J, Choonara I. Safety in paediatric clinical trials-a 7-year review. Acta Paediatr. 2008;97:474-7.

Klassen TP, Hartling L, Craig JC, Offringa M. Children are not just small adults: the urgent need for high-quality trial evidence in children. PLoS Med. 2008;5(8):e172.

Curran WJ. The thalidomide tragedy in Germany: the end of a historic medicolegal trial. N Engl J Med. 1971;284:481-2.

Tull DS, Hawkins DI. Marketing research, 57-6th ed. Macmillan. 1998.

The World Bank. Population ages 0-14 (% of total). The United Nations population division’s world population prospects. 2011. Available at: indicator/SP.POP.0014.TO.ZS/countries/1W?display= default. Accessed on 6 June, 2022.

International Clinical Trials Registry Platform (ICTRP). Available at: Accessed on 6 March, 2020.

Joseph PD, Craig JC, Caldwel PHY. Clinical trials in children. Br J Clin Pharmacol. 2013;79(3):357-69.

Fleischman AR, Collogan LK. Research with Children. In: Emanuel EJ, Grady C, Crouch RA, Lie RK, Miller FG, Wendler D, editors. The Oxford Textbook of Clinical Research. New York: Oxford University Press. 2008;446-60.

World Medical Association. BMJ. vol 2. Helsinki, Finland: WMA; 1964. Code of Ethics of the World Medical Association: Declaration of Helsinki. 1964;177.

Krugman S, Giles JP, Hammond J. Infectious hepatitis: Evidence for two distinct clinical, epidemiological, and immunological types of infection. JAMA. 1967;200:365-73.

Tuskegee University. About the USPHS Study. Available at: Accessed on 6 June, 2022.

The National Commission for the Protection of the Human Subjects of Biomedical and Behavioral Research. The Belmont Report: Ethical Principles and Guidelines for Protection of Human Subjects of Research. US Department of Health and Human Services. Available at: belmont.html. Accessed on 6 June, 2022

Bavdekar SB. Pediatric clinical trials. Perspect Clin Res. 2013;4(1):89-9.

Steinbrook R. Testing Medications in Children. N Eng J Med. 2002;347(18):1462-70.

United S. Research involving children: report and recommendations. Bethesda, Md: The Commission. 1977.

Westra AE, Wit JM, Sukhai RN, de Beaufort ID. How Best to Define the Concept of Minimal risk. J Pediatr. 2011;159(3):496-500.

Shah S, Whittle A, Wilfond B, Gensler G, Wendler D. How Do Institutional Review Boards Apply the Federal Risk and Benefit Standards for Pediatric Research? J Am Med Asso. 2004;291(4):476-82.

Jonsen AR. Research Involving Children: Recommendations of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. Pediatrics. 1978;62(2):131-6.

Shaddy RE, Denne SC. The Committee on Drugs and Committee on Pediatric Research. Clnical Report- Guidelines for the Ethical Conduct of Studies to Evaluate Drugs in Pediatric Populations. Pediatrics. 2010;125(4):850-60.

Gill D, Kurz R. Practical and Ethical Issues in Pediatric Clinical Trials. Appl Clin Trials. 2003;12:41-4.

Amin SB, McDermott MP, Shamoo AE. Clinical trials of drugs used off-label in neonates: Ethical issues and alternative study designs. Account Res. 2008;15:168-87.

Shilling V, Williamson RP, Hickey H, Sowden E, Smyth RL, Young B. Processes in recruitment to randomized controlled trials of medicines for children (RECRUIT): A qualitative study. Health Technol Assess. 2011;15:1-116.

Ethical Guidelines for Biomedical Research on Human Participants. New Delhi: Indian Council of Medical Research; 2006. Indian Council of Medical Research. Available at: Accessed on 6 June 2022.

American Academy of Pediatrics Committee on Drugs. Guidelines for the ethical conduct of studies to evaluate drugs in pediatric populations. Pediatrics. 1995;95:286-94.

Kimberly MB, Hoehn KS, Feudtner C, Melson RM, Schreiner M. Variation in standards of research compensation and child assent practices: A comparison of 69 institutional review board-approved informed permission and assent forms for 3 Multicenter Pediatric Clinical Trials. Pediatrics. 2006;117:1706-11.

Baines P. Assent for Children's participation in research is incoherent and wrong. Arch Dis Child. 2011;96:960-2.

Wendler D, Shah S. Should children decide whether they are enrolled in nonbeneficial research? Am J Bioeth. 2003;3:1-7.

Stenson BJ, Becher JC, McIntosh N. Neonatal research: the parental perspective. Arch Dis Child Fetal Neonatal Ed. 2004;89:F321-4.

Snowdon C, Harvey SE, Brocklehurst P, Tasker RC, Platt MP, Allen E et al. The BRACELET Study: Survey of mortality in UK neonatal and paediatric intensive care trials. Trials. 2010;11:65.

Christopher M. Wittich, MD, PharmD; Christopher M. Burkle, MD, JD; and William L. Lanier, MD. Ten Common Questions (and Their Answers) About Off-label Drug Use. Mayo Clin Proc. 2012;87(10):982-90

Committee on drugs. Off-Label Use of Drugs in Children. Pediatrics. 2014;133(3):563-7.

Laventhal N, Tarini B, Lantos J. Ethical Issues in Neonatal and Pediatric Clinical Trials. Pediatr Clin North Am. 2013;59(5):1205-20.