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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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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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