regulation of clinical trials in paediatric population differences between trials in adults and...

REGULATION OF CLINICAL TRIALS IN PAEDIATRIC POPULATION

DIFFERENCES BETWEEN TRIALS IN ADULTS AND CHILDREN

presented byGYURASICS, ÁGNES MD PhD

National Institute for Quality- and Organizational Development in Healthcare and MedicinesNATIONAL INSTITUTE OF PHARMACY

BUDAPEST, HUNGARY

2

SALUS AEGROTI SUPREMA LEX

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

IMPLEMENTATION – APPLICATIONS’ Number

6

IMPORTANT THERAPEUTIC

AREAS

(dark:PIPsgrey: full waivers)

7

ABSOLUTE NUMBER OF PAEDIATRIC TRIALS

8

RELATIVE NUMBER OF PAEDIATRIC TRIALS

9

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

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

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

CLINICAL TRIALSDIFFERENCES 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

CLINICAL TRIALSDIFFERENCES 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

CLINICAL TRIALSDIFFERENCES 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

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

16

17

IF YOU DESIGN FOR THE OLD, YOU INCLUDE THE YOUNG

- IF YOU DESIGN FOR THE YOUNG, YOU

EXCLUDE THE OLD

BERNARD ISAACS

18

19

20

THANK YOU

• AGNES SAINT RAYMOND• THORSTEN OLSKI