Module232025

5/7/2025

Comparator

• Randomised comparison is usually required • Use of placebo:  Often (over)stated ethical issues but depends on disease severity and available SOC,  higher placebo responses in CTs in children as compared to adults  as add-on to SOC, short duration, unequal allocation, escape criteria • Selection of active comparator  Not necessarily licensed but depends on evidence for the comparator  Use based in label and/or clinical guidelines in all centres  Investigator’s best choice / best supportive care standardised across centres • Double-blinding is preferred to reduce bias but can be challenging • Use of historical control in rare diseases and RWE

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End-points • Primary endpoint(s) should be clinically meaningful  Paeds QOL and/or PRO data collected - instruments suitable for age ranges studied • Timing of measurement / Study duration  when the effect of the drug is expected, what it means for disease  Specific long term follow up as part of the MA should be discussed – open label extension  Take into consideration relapse rate/rebound/maintenance of effect, evolution of disease in children can be slower • It may be necessary to develop, validate, and employ age-appropriate scales or endpoints • Regulatory agreement for use of surrogate or composite endpoints and biomarkers without precedent

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