Abstract
Treatment of children with effective and safe medicines is crucial to improve their outcome. Despite this relevance, it is still common practice in children to administer medicines outside their market authorization. Even if authorized, pediatric medicines may not be age-appropriate for a broad range of therapeutic areas. This has been recognized as very unsatisfactory by all stakeholders involved and makes clinical pharmacological studies in children an obvious need.
However, clinical trials of medicines in children come with their specific burdens. These burdens can be qualified as either related to the specific aspects of pediatric pharmacokinetics (PK) and pharmacodynamics (PD) or relate to the logistics of clinical trials of medicines in children. This is followed by a stakeholder’s analysis, discussing specific aspects related to parents and their children (International Children’s Advisory Network, iCAN), recruitment challenges, and research capacity building. We hereby tried to focus on recent evolutions, including initiatives to further develop this research capacity (Institute for Advanced Clinical Trials, iACT for children; Innovative Medicines Initiative, IMI2).
Perhaps progress is slower than anticipated, but pediatric medicines research is evolving, and we should keep this momentum. A further structured collaboration between the different stakeholders involved (the society, parents and children, sponsors, regulatory authorities) at the international level is crucial to use the available, but limited, resources as effective as possible to further improve pharmaceutical care in children.
References and Further Reading
Allegaert K, van den Anker J (2015) Neonatal drug therapy: the first frontier of therapeutics for children. Clin Pharmacol Ther 98:288–297
Caldwell PH, Butow PN, Craig JC (2002) Pediatricians’ attitudes toward randomized controlled trials involving children. J Pediatr 141:798–803
Cherrill J, Hudson H, Cocking C et al (2010) Clinical trials: the viewpoint of children with a chronic illness compared with healthy children. Arch Dis Child 95:229–232
Cliff-Eribo KO, Sammons H, Choonara I (2016) Systematic review of paediatric studies of adverse drug reactions from pharmacovigilance databases. Exp Opinin Drug Saf 15:1321–1328
Critical Path Institute (2015) https://c-path.org/programs/inc. Accessed 21 Jul 2017
De Cock RF, Piana C, Krekels EH et al (2011) The role of population PK–PD modelling in paediatric clinical research. Eur J Clin Pharmacol 67(Suppl 1):5–16
Doussau A, Geoerger B, Jimenez I et al (2016) Innovations for phase I dose-finding designs in pediatric oncology clinical trials. Contemp Clin Trials 47:217–227
European Commission (2016) http://ec.europa.eu/research/participants/portal/desktop/en/opportunities/h2020/topics/imi2-2016-10-04.html. Accessed 21 Jul 2017
European Medicines Agency (2016a) http://ec.europa.eu/health//sites/health/files/files/paediatrics/2016_pc_report_2017/ema_10_year_report_for_consultation.pdf. Accessed 21 Jul 2017
European Medicines Agency (2016b) http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2016/07/WC500211315.pdf. Accessed 21 Jul 2017
European Network of Paediatric Research at the European Medicines Agency (2012) http://www.ema.europa.eu/ema/index.jsp?curl=pages/partners_and_networks/general/general_content_000303.jsp. Accessed 21 Jul 2017
Gonzalez D, Paul IM, Benjamin DK Jr et al (2014) Advances in pediatric pharmacology, therapeutics, and toxicology. Adv Pediatr Infect Dis 61:7–31
Hampson LV, Herold R, Posch M et al (2014) Bridging the gap: a review of dose investigations in paediatric investigation plans. Br J Clin Pharmacol 78:898–907
Hein IM, Troost PW, de Vries MC et al (2015) Why do children decide not to participate in clinical research: a quantitative and qualitative study. Pediatr Res 78:103–108
Hellstrom A, Ley D, Hansen-Pupp I et al (2016) Insulin-like growth factor 1 has multisystem effects on foetal and preterm infant development. Acta Paediatr 105:576–586
Hoberman A, Shaikh N, Bhatnagar S et al (2013) Factors that influence parental decisions to participate in clinical research: consenters vs nonconsenters. JAMA Pediatr 167:561–566
Hoppu K, Anabwani G, Garcia-Bournissen F et al (2012) The status of paediatric medicines initiatives around the world – what has happened and what has not? Eur J Clin Pharmacol 68:1–10
Horen B, Montastruc JL, Lapeyre-Mestre M (2002) Adverse drug reactions and off-label drug use in paediatric outpatients. Br J Clin Pharmacol 54:665–670
International Children’s Advisory Network (2016) https://www.icanresearch.org. Accessed 21 Jul 2017
Janiaud P, Cornu C, Lajoinie A et al (2017) Is the perceived placebo effect comparable between adults and children ? A meta-regression analysis. Pediatr Res 81:11–17
Joseph PD, Craig JC, Caldwell PH (2015) Clinical trials in children. Br J Clin Pharmacol 79:357–369
Kearns GL (2010) Beyond biomarkers: an opportunity to address the ‘pharmacodynamic gap’ in pediatric drug development. Biomark Med 4:783–786
Léauté-Labrèze C, Harper JI, Hoeger PH (2017) Infantile haemangioma. Lancet 390:85–94
Lepola P, Needham A, Mendum J et al (2016) Informed consent for paediatric clinical trials in Europe. Arch Dis Child 101:1017–1025
Magalhaes J, Rodrigues AT, Rogue F et al (2015) Use of off-label and unlicensed drugs in hospitalized paediatric patients: a systematic review. Eur J Clin Pharmacol 71:1–13
Manolis E, Pons G (2009) Proposals for model-based paediatric medicinal development within the current European Union regulatory framework. Br J Clin Pharmacol 68:493–501
Momper JD, Mulugeta Y, Burckart GJ (2015) Failed pediatric drug development trials. Clin Pharmacol Ther 98:245–251
Mühlbauer B, Janhsen K, Pichler J et al (2009) Off-label of prescription drugs in childhood and adolescence: an analysis of prescription patterns in Germany. Dtsch Arztebl Int 106:25–31
Nguyen TT, Jayadeva V, Cizza G et al (2014) Challenging recruitment of youth with type 2 diabetes into clinical trials. J Adolesc Health 54:247–254
Randolph AG (2009) The unique challenges of enrolling patients into multiple clinical trials. Crit Care Med 37(1 Suppl):S107–S111
Ravindranath Y (2015) Evolution of modern treatment of childhood acute leukemia and cancer: adventures and battles in the 1970s and 1980s. Pediatr Clin N Am 62:1–10
Reed MD (2011) Reversing the myths obstructing the determination of optimal age- and disease-based drug dosing in pediatrics. J Pediatr Pharmacol Ther 16:4–13
Regulatory Affairs Professionals Society (2016) http://www.raps.org/Regulatory-Focus/News/2016/01/29/24212/FDA-NIH-Unveil-Glossary-of-Clinical-Definitions. Accessed 21 Jul 2017
Saint-Raymond A, Pelle B, Zaccaria C et al (2016) Usage of unpublished paediatric data. Arch Dis Child 101:81–84
Sammons HM, Atkinson M, Choonara I et al (2007) What motivates British parents to consent for research? A questionnaire study. BMC Pediatr 7:12
Schachter AD, Ramoni MF (2007) Paediatric drug development. Nat Rev Drug Discov 6:429–430
Stiers JL, Ward R (2014) Newborns, one of the last therapeutic orphans to be adopted. JAMA Pediatr 168:106–108
Tromp K, Zwaan CM, van de Vathorst S (2016) Motivations of children and their parents to participate in drug research: a systematic review. Eur J Pediatr 175:599–612
Turner MA, Portman RJ, Davis JM (2017) Regulatory science in neonates: a framework that supports evidence-based drug therapy. JAMA Pediatr. https://doi.org/10.1001/jamapediatrics.2017.1360
United States National Institutes of Health (2017) https://www.clinicaltrials.gov/ct2/search. Accessed 15 Jul 2017
Van Riet-Nales DA, de Jager KE, Schobben AF et al (2011) The availability and age-appropriateness of medicines authorized for children in the Netherlands. Br J Clin Pharmacol 72:465–473
Vassal G, Rousseau R, Blanc P et al (2015) Creating a unique, multi-stakeholder Paediatric Oncology Platform to improve drug development for children and adolescents with cancer. Eur J Cancer 51:218–224
Wharton GT, Murphy MD, Avant D et al (2014) Impact of pediatric exclusivity on drug labeling and demonstrations of efficacy. Pediatrics 134:e512–e518
Woolfall K, Shilling V, Hickey H et al (2013) Parents’ agendas in paediatric clinical trial recruitment are different form researchers’ and often remain unvoiced: a qualitative study. PLoS One 8:e67352
World Health Organization (2012) http://www.who.int/medicines/areas/quality_safety/safety_efficacy/EMP_ConsumerReporting_web_v2.pdf. Accessed 21 Jul 2017
World Health Organization (2017) http://www.who.int/medicines/publications/essentialmedicines/6th_EMLc2017.pdf. Accessed 21 Jul 2017
Acknowledgments
The clinical research activities of Karel Allegaert are facilitated by the agency for innovation by Science and Technology in Flanders (IWT) through the SAFEPEDRUG project (IWT/SBO 130033).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer International Publishing AG
About this entry
Cite this entry
Allegaert, K. (2017). Clinical Studies in Infants (Pediatric Pharmacology). In: Hock, F., Gralinski, M. (eds) Drug Discovery and Evaluation: Methods in Clinical Pharmacology. Springer, Cham. https://doi.org/10.1007/978-3-319-56637-5_44-1
Download citation
DOI: https://doi.org/10.1007/978-3-319-56637-5_44-1
Received:
Accepted:
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-56637-5
Online ISBN: 978-3-319-56637-5
eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences