European Journal of Clinical Pharmacology

, Volume 64, Issue 2, pp 201–205 | Cite as

Paediatric clinical pharmacology—at the beginning of a new era

Special Article

Abstract

The lack of availability of medicines for children is a large problem. This problem is global. It concerns all children of the world, those in the developing world but also those in the developed world, even in the richest countries. Many generations of paediatricians and other physicians have learned to live with the situation, where more than half of the children are prescribed off-label or unlicensed medicines. However, there is no doubt that medicinal products used to treat the paediatric population should be subjected to ethical research of high quality and be appropriately authorised for use in the paediatric population. Within the last 10 years, the pioneering paediatric initiative in the United States and recent encouraging developments in Europe and at the WHO indicate that change may finally be possible. The developments of the last 2 years have been particularly intensive. It seems that a new era is beginning which will provide unprecedented opportunities but also great challenges for paediatric clinical pharmacologists and other stakeholders working to provide children with the medicines they need.

References

  1. 1.
    Dost FH, Repges R (1968) Zur Beschreibung der Pharmakokinetik der Bromsulphalein-Ausscheiding unter Verwendung des Analog-Computers. Pharmacologia Clinica (Eur J Clin Pharmacol) 1(1):1–7CrossRefGoogle Scholar
  2. 2.
    Silverman W, Andersen D, Blanc W, Crozier D (1956) A difference in mortality rate and incidence of kernicterus among premature infants allotted to two prophylactic antibacterial regimens. Pediatrics 18:614–625PubMedGoogle Scholar
  3. 3.
    Burns L, Hodgman J, Cass A (1959) Fatal circulatory collapse in premature infants receiving chloramphenicol. N Engl J Med 261(26):1318–1321PubMedCrossRefGoogle Scholar
  4. 4.
    Krauer B, Spring P, Dettli L (1968) Zur Pharmakokinetik der Sulphonamide im ersten Lebensjahr. Pharmacologia Clinica (Eur J Clin Pharmacol) 1:47–53CrossRefGoogle Scholar
  5. 5.
    (1980) European Journal of Clinical Pharmacology 18(1):1–128Google Scholar
  6. 6.
    Kearns GL, Abdel-Rahman SM, Alander SW, Blowey DL, Leeder JS, Kauffman RE (2003) Developmental pharmacology—drug disposition, action, and therapy in infants and children. N Engl J Med 349(12):1157–1167PubMedCrossRefGoogle Scholar
  7. 7.
    Jacqz-Aigrain E, Choonara I (eds) (2006) Paediatric clinical pharmacology. Informa HealthcareGoogle Scholar
  8. 8.
    Yaffe SJ, Aranda JV (eds) (2005) Neonatal and pediatric pharmacology. Therapeutic principles in practice. Lippincott Williams & Wilkins, PhiladelphiaGoogle Scholar
  9. 9.
    Gill D (2004) Ethical principles and operational guidelines for good clinical practice in paediatric research. Recommendations of the Ethics Working Group of the Confederation of European Specialists in Paediatrics (CESP). Eur J Pediatr 163(2):53–57PubMedCrossRefGoogle Scholar
  10. 10.
    Abdel-Rahman SM, Reed MD, Wells TG, Kearns GL (2007) Considerations in the rational design and conduct of phase I/II pediatric clinical trials: avoiding the problems and pitfalls. Clin Pharmacol Ther 81(4):483–494PubMedCrossRefGoogle Scholar
  11. 11.
    Caldwell PH, Murphy SB, Butow PN, Craig JC (2004) Clinical trials in children. Lancet 364(9436):803–811PubMedCrossRefGoogle Scholar
  12. 12.
    Schreiner MS (2003) Paediatric clinical trials: redressing the imbalance. Nat Rev Drug Discov 2(12):949–961PubMedCrossRefGoogle Scholar
  13. 13.
    Steinbrook R (2002) Testing medications in children. N Engl J Med 347(18):1462–1470PubMedCrossRefGoogle Scholar
  14. 14.
    Fanta S, Jönsson S, Backman J, Karlsson M, Hoppu K (2007) Developmental pharmacokinetics of ciclosporin—a population pharmacokinetic study in paediatric renal transplant candidates. Br J Clin Pharmacol. DOI  10.1111/j.1365-2125.2007.03003.x
  15. 15.
    Blake MJ, Gaedigk A, Pearce RE, Bomgaars LR, Christensen ML, Stowe C, James LP, Wilson JT, Kearns GL, Leeder JS (2007) Ontogeny of dextromethorphan O- and N-demethylation in the first year of life. Clin Pharmacol Ther 81(4):510–516PubMedCrossRefGoogle Scholar
  16. 16.
    Balakrishnan K, Grieve J, Tordoff J, Norris P, Reith D (2006) Pediatric licensing status and the availability of suitable formulations for new medical entities approved in the United States between 1998 and 2002. J Clin Pharmacol 46(9):1038–1043PubMedCrossRefGoogle Scholar
  17. 17.
    Hoppu K, Jaakkola R (1996) Children. The orphans of drug therapy—a longstanding, still current problem (in Finnish with English summary). TABU 4(5):6–10Google Scholar
  18. 18.
    Chui J, Tordoff J, Kennedy J, Reith D (2004) Trends in accessibility to medicines for children in New Zealand: 1998–2002. Br J Clin Pharmacol 57(3):322–327PubMedCrossRefGoogle Scholar
  19. 19.
    Ceci A, Felisi M, Baiardi P, Bonifazi F, Catapano M, Giaquinto C, Nicolosi A, Sturkenboom M, Neubert A, Wong I (2006) Medicines for children licensed by the European Medicines Agency (EMEA): the balance after 10 years. Eur J Clin Pharmacol 62(11):947–952PubMedCrossRefGoogle Scholar
  20. 20.
    Conroy S, Choonara I, Impicciatore P, Mohn A, Arnell H, Rane A, Knoeppel C, Seyberth H, Pandolfini C, Raffaeli M, Rocchi F, Bonati M, Jong G, de Hoog M, van den Anker J (2000) Survey of unlicensed and off label drug use in paediatric wards in European countries. BMJ 320:79–82PubMedCrossRefGoogle Scholar
  21. 21.
    ’t Jong GW, Vulto AG, de Hoog M, Schimmel KJM, Tibboel D, van den Anker J (2001) A survey of the use of off-label and unlicensed drugs in a Dutch children’s hospital. Pediatrics 108:1089–1093PubMedCrossRefGoogle Scholar
  22. 22.
    American Academy of Pediatrics, Committee on Drugs (2002) Uses of drugs not prescribed in the package insert (off-label uses). Pediatrics 110(1):181–183CrossRefGoogle Scholar
  23. 23.
    Gazarian M, Kelly M, McPhee JR, Graudins LV, Ward RL, Campbell T (2006) Off-label use of medicines: consensus recommendations for evaluating appropriateness. Med J Austr 185(10):544–548Google Scholar
  24. 24.
    Balakrishnan K, Tordoff J, Norris P, Reith D (2007) Establishing a baseline for the monitoring of medicines availability for children in the UK: 1998–2002. Br J Clin Pharmacol 63(1):85–91PubMedCrossRefGoogle Scholar
  25. 25.
    Choonara I, Conroy S (2002) Unlicensed and off-label drug use in children: implications for safety. Drug Saf 25(1):1–5PubMedCrossRefGoogle Scholar
  26. 26.
    Roberts R, Rodriguez W, Murphy D, Crescenzi T (2003) Pediatric drug labeling. Improving the safety and efficacy of pediatric therapies. JAMA 290(7):905–911PubMedCrossRefGoogle Scholar
  27. 27.
    Ward RM, Kauffman R (2007) Future of pediatric therapeutics: reauthorization of BPCA and PREA. Clin Pharmacol Ther 81(4):477–479PubMedCrossRefGoogle Scholar
  28. 28.
    Li JS, Eisenstein EL, Grabowski HG, Reid ED, Mangum B, Schulman KA, Goldsmith JV, Murphy MD, Califf RM, Benjamin DK Jr (2007) Economic return of clinical trials performed under the pediatric exclusivity program. JAMA 297(5):480–488PubMedCrossRefGoogle Scholar
  29. 29.
    (2006) Regulation (EC) no 1901/2006 of the European Parliament and of the Council on Medicinal Products for Paediatric Use and Amending Regulation (EEC) no. 1768/92, Directive 2001/20/EC, Directive 2001/83/EC and Regulation (EC) no. 726/2004. http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-1/reg_2006_1901/reg_2006_1901_en.pdf)
  30. 30.
    Dunne J (2007) The European regulation on medicines for paediatric use. Paed Resp Rev 8(2):177–183CrossRefGoogle Scholar
  31. 31.
    Chui J, Tordoff J, Reith D (2005) Changes in availability of paediatric medicines in Australia between 1998 and 2002. Br J Clin Pharmacol 59(6):736–742PubMedCrossRefGoogle Scholar
  32. 32.
    (2007) Resolution WHA60.20: Better medicines for children. http://www.who.int/gb/ebwha/pdf_files/WHA60/A60_R20-en.pdf)
  33. 33.
    Hill S, Gray A, Weber M (2007) Setting standards for essential children’s medicines. Bull World Health Organ 85(9):650PubMedCrossRefGoogle Scholar
  34. 34.
    Cohen SN (1999) The Pediatric Pharmacology Research Unit (PPRU) Network and its role in meeting pediatric labeling needs. Pediatrics 104(3 Pt 2):644–645PubMedGoogle Scholar
  35. 35.
    Bonati M, Breitkreutz J, Choonara I, Hoppu K, Jacqz-Aigrain E, Langendries J-P, Pons G, Rane A, Seyberth H, van den Acker J (2006) Paediatric clinical pharmacology in Europe. Paed Perinat Drug Ther 7(3):134–137CrossRefGoogle Scholar
  36. 36.
    Peto R, Baigent C (1998) Trials: the next 50 years. Large scale randomised evidence of moderate benefits. BMJ 317(7167):1170–1171PubMedGoogle Scholar
  37. 37.
    Committee For Medicinal Products For Human Use (CHMP) (2006) Guideline on clinical trials in small populations (CHMP/EWP/83561/2005). European Medicines Agency, LondonGoogle Scholar
  38. 38.
    (2007) Promoting safety of medicines for children. WHO, GenevaGoogle Scholar
  39. 39.
    Mathis LL, Iyasu S (2007) Safety monitoring of drugs granted exclusivity under the Best Pharmaceuticals for Children Act: what the FDA has learned. Clin Pharmacol Ther 82(2):133–134PubMedCrossRefGoogle Scholar
  40. 40.
    Committee For Medicinal Products For Human Use (CHMP) (2007) Guideline on conduct of pharmacovigilance for medicines used by the paediatric population (EMEA/CHMP/PhVWP/235910/2005-rev.1). European Medicines Agency, London. http://www.emea.europa.eu/pdfs/human/phvwp/23591005enfinal.pdf)
  41. 41.
    Hoppu K (2006) 2006: An exceptional year for international paediatric clinical pharmacology. Pharmacol Int (67):6–7Google Scholar
  42. 42.
    Stephenson T (2007) “Bonne Annee”, “Gutes Neues Jahr”? Will 2007 be a “Happy New Year” for children’s medicines in Europe? Arch Dis Child 92(8):661–663PubMedCrossRefGoogle Scholar
  43. 43.
    MacLeod S, Peterson R, Wang Y, Li Z, Gui Y, Schaller J (2007) Challenges in international pediatric pharmacology. A milestone meeting in Shanghai. Ped Drugs 9(4):215–218CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Poison Information CentreHelsinki University Central HospitalHelsinkiFinland
  2. 2.Hospital for Children and AdolescentsUniversity of HelsinkiHelsinkiFinland
  3. 3.Department of Clinical PharmacologyUniversity of HelsinkiHelsinkiFinland

Personalised recommendations