1. Pediatric pharmacology: why do we need it ?
Milica Bajcetic, MD,PhD
ESDP
Departrment for Clinical Research
University Children’s Hospital
& Department for Pharmacology,
Clinical Pharmacology and Toxicology
School of Medicine, University of Belgrade

2. Timeline 1930s beginning of development of Clinical Pharmacology (CP)
Harry Gold ( ) Cornell University, USA
1930s beginning of development of Clinical Pharmacology (CP)
1952, Harry Gold established CP
1960, Journal of Clinical Pharmacology & Therapeutics
1970, CP unit established in Nordic countries, UK and USA
“…a special kind of investigator is required, one whose training has equipped him not only with the principles and techniques of laboratory pharmacology but also with knowledge of clinical medicine…”

3. CP postgraduate programme in Serbia
1975, School of Medicine, University of Novi Sad
1981, School of Medicine, University of Belgrade
Until today more than 90 CP specialists and subspecialists fully trained

4. CP UNIT IN SERBIA 1989, Institute for Oncology
and Radiology of Serbia, Belgrade
2005, Military Medical Academy
2003, Clinical Center of Serbia, Belgrade
1995, Clinical Center, Kragujevac
2008, University Children’s Hospital, Belgrade
2004, Center for Pharmacotherapy, Clinical Center, Niš

5. 1930 - diethylene glycol poisoning - deaths
chloramphenicol - gray baby syndrome
thalidomide – phocomelia, etc.

6. Licensing system – ensures that medicines are examined for:
Safety
Quality
Efficacy

7. RANDOMIZED,CONTROLLED CLINICAL TRIAL
pharmacokinetics
pharmacodynamics
pharmacogenetics
PHARMACOVIGILANCE
PHARMACOEPIDEMIOLOGY
PHARMACOECONOMY

8. RANDOMIZED,CONTROLLED CLINICAL TRIAL
EXTRAPOLATION
EXPERIENCE
SENSATION
pharmacokinetics
pharmacodynamics
pharmacogenetics
PHARMACOVIGILANCE
PHARMACOEPIDEMIOLOGY
PHARMACOECONOMY

9. 50-90% of medicines used have never actually been studied in children!

10. and psychological differences from adults.
Children are vulnerable population with:
developmental
physiological
and psychological differences from adults.

11. Absence of PK/PD/PG data →unreliable dose
Safety and efficacy have not been assessed
Lack of suitable pediatric formulations
Absence of clinical trials in children leads to the use of off-label and unlicensed drugs

12. Fig. 2: Percentages of availabilty:
Availability of oral formulation suitable for use in children in Serbia, Germany and USA
Fig. 2.1.
Percentage of active substances in a suitable oral dosage form
Fig. 2.2.
Percentage of active substances in a suitable oral dosage form and labelled for pediatrics < 12 years
Fig. 2.3
Percentage of labelled active substances in the group of active substances in suitable oral dosage form

13. Off-label/Unlicensed Rates of Prescription%
Ratio of Children Undergoing Off label/Unlicensed Drug Use %

14. Most Common Reason For Off Label Drug Use

15. OFF LABEL/UNLICENSED USE
benefit
harm
no effect
SUB DOSING OVER
LACK OF PK/PD/PG DATA
ADRs

16. Off-label/Unlicensed drug use and ADRs%

17. Doctors are men who prescribe medicines of which they know little, to cure diseases of which they know less, in human beings of whom they know nothing.
Voltaire ( )

18. What is being done about this situation?

19. Closing the gap-USA legislation
2002 Best Pharmaceutical for Children Act
2003 Pediatric Research Equity Act
1998 Pediatric “Final Rule”
1997 Pediatric Exclusivity provision
1994 FDA Pediatric Rule
1992 Pediatric Pharmacology Research Network.Today 13 centers
FDA Pediatric exlusivity labeling changes
Up to
New doses,new precautions
Drug studies included multiple therapeutic areas
Studies included efficacy/safety,PK,PD
Adressing unmet therapeutic need in children with diverse condition

20. EUROPE: SIGNS OF PROGRESS
1997 EMEA Note for guidance on clinical investigation of medical products in the pediatric population
1998 European Network for Drug Investigation in Children (Finland, France, Germany, Israel, Italy, the Netherlands, Sweden, Switzerland, UK)
2001 International Conference on Harmonisation ICH
2002 European Forum for Good Clinical Practice CESP: Better Medicines for Children 2001
2004 EU Commission released the first proposal for a Regulation on Medicinal Products for Paediatric Use
2006 Regulation agreed on June 1, 2006.
2007 January, Clinical drug researches in pediatrics allowed