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

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SALUS AEGROTI SUPREMA LEX

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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

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IMPLEMENTATION – APPLICATIONS’ Number

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IMPORTANT THERAPEUTIC

AREAS

(dark:PIPsgrey: full waivers)

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ABSOLUTE NUMBER OF PAEDIATRIC TRIALS

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RELATIVE NUMBER OF PAEDIATRIC TRIALS

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

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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

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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

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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

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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?...

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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?

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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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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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THANK YOU

• AGNES SAINT RAYMOND• THORSTEN OLSKI