1. REGULATION OF CLINICAL TRIALS IN PAEDIATRIC POPULATION DIFFERENCES BETWEEN TRIALS IN ADULTS AND CHILDREN presented by GYURASICS, ÁGNES MD PhD National Institute for Quality- and Organizational Development in Healthcare and Medicines NATIONAL INSTITUTE OF PHARMACY BUDAPEST, HUNGARY

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3. SALUS AEGROTI SUPREMA LEX

4. 4 THREE YEARS OF PAEDIATRIC REGULATION IN THE EUROPEAN UNION Thorsten M. Olski & Simona F. Lampus &Giulia Gherarducci & Agnes Saint Raymond EurJ Clin Pharmacol 2011, 67:245-252 Reg (EC) 1901/2006

5. 5 IMPLEMENTATION – APPLICATIONS’ Number

6. 6 IMPORTANT THERAPEUTIC AREAS (dark:PIPs grey: full waivers)

7. 7 ABSOLUTE NUMBER OF PAEDIATRIC TRIALS

8. 8 RELATIVE NUMBER OF PAEDIATRIC TRIALS

9. 9 DEFERRAL TIME GRANTED (grey: Art7, dark: Art8)

10. 10 NUMBER OF PAEDIATRIC TRIALS -absolute number fairly constant -relative number increased -deferrals have been granted -longer time for new applications (Art7) -time lag between approval of a PIP and the initiation of the respective trial

11. 11 IN GENERAL… most important therapeutic areas are covered large number of age-appropriate formulations (23%) good coverage of age groups including neonates (26%) PDCO has to request major modifications (38%) in many proposals proportion of paediatric trials has increased

12. 12 CLINICAL TRIALS DIFFERENCES from ADULTS fast changing physiology – –growth, maturation –neurobehavioural, psychosexual aspects developmental phases crossed during the study –interference with them pathology: often faster progressing than in adults EndPoints? E/S – might differ –by age category –vs adults extrapolation? –EFFICACY - often possible –SAFETY – long term pediatric data needed for chronic conditions

13. 13 CLINICAL TRIALS DIFFERENCES from ADULTS adolescents: complience?! … staggered approach down by age age appropriate formulations small patient populations – feasibility issues? –„more drugs than patients” ethical issues - differences regarding –geographical areas –perception of risk: parents: sec age af the child –consent; assent: age of involvement of the paediatric patient?...

14. 14 CLINICAL TRIALS DIFFERENCES from ADULTS design PDCO requested more trials to be –placebo controlled –staggered approach dosing: exposure/response based? modeling and simulation needed specimen available for analysis? micromethods as much good data to produce with as few patients as possible often as subgroup of adults’ (PhIII) trials B/R; risk minimization measures ethical considerations: –harmonization? assent ? –trials outside of EU?

15. 15 IN SUMMARY vs adults: relatively few available patients in paediatrics much variability (development – maturation; progression) well designed focused trials needed: –modeling and simulation preferred; open label extension: might convince participants /parents feasibility? recruitement, retainement in trials placebo? ethical issues training: investigators, patients, parents transparency, communication to the public

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17. 17 IF YOU DESIGN FOR THE OLD, YOU INCLUDE THE YOUNG - IF YOU DESIGN FOR THE YOUNG, YOU EXCLUDE THE OLD BERNARD ISAACS

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20. 20 THANK YOU AGNES SAINT RAYMOND THORSTEN OLSKI