Module232025

07/05/2025

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

1. Comparator or Control Group (placebo, different condition) 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

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The Placebo Problem

From Ethics Guideline for performing Clinical Trials with Minors: 9.2 Paediatric control groups The use of control groups, including the use of placebo, should be based on equipoise, should be appropriate to the condition(s) under investigation in the trial, and should be justified scientifically. 9.2.1 Use of placebo Placebo should not be used when it means withholding effective treatment, particularly for serious and life-threatening conditions. However, the use of placebo may be warranted in children as in adults when evidence for any particular treatment is lacking or when the placebo effect is known to be very variable (e.g. pain, hay fever). As the level of evidence in favour of an effective treatment increases, the ethical justification for placebo use weakens. Long-term use (beyond 3-6 months) of placebo is known to create difficulties in acceptance of the trial by participants and to increase drop-out rates.

The Organisation for Professionals in Regulatory Affairs

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