Module232025

07/05/2025

ETHICS CHALLENGES IN PAEDIATRIC CLINICAL TRIALS My personal top 10 (based on ~600 protocols reviewed 2017-2023)

2. Blood Sample Volumes (excessive, EU < US guidance, heel stabs) 3 Study Burden: Visit Duration, Content and Schedule 4 Intrusive Assessments (Tanner staging) 5 Endpoints (adult, not child, medical review for SAEs) 6 Pregnancy (child privacy, post-trial follow-up, pregnant partner) 7. Post-Trial Access to IMP (protocol ambiguous or silent, toxicology) 8. Communication of Trial Results (onus on participants, child to adult) 9. “Aging Out” (no process, incorrect process) 10. Paediatric Assent and Information Sheets (length, complexity)

The Organisation for Professionals in Regulatory Affairs

33

Blood volumes, patient and parent burden

Study Burden

Blood volumes − How many heel stabs will you permit for newborns? – Most ECs limit to 3 − Day 1 often problematic (e.g., >80% TBV required) • 24-hr limits: EU Guidance is 1% of TBV; US Guidance is 2 mL/kg or 2.5% of TBV − Population PK approach, but requires more children in study – finding a balance − TASSO ® devices – take capillary blood, so assays may need to be re-validated − Remember trial samples are in addition to clinical samples

34

17