TY - JOUR
T1 - Points to consider when initiating clinical investigations in autistic paediatric populations–A White Paper
AU - Ham, Lindsay M.
AU - Staunton, Hannah
AU - Schulz, Jan Michael
AU - Tillmann, Julian
AU - Volz, Dietmar
AU - Murtagh, Lorraine
AU - Chatham, Christopher
AU - O'Connor, Eoin C.
AU - Chamberlain, Stormy
AU - Schoenenberger, Philipp
AU - Pandina, Gahan
AU - Wang, Paul
AU - Kas, Martien J.H.
AU - Arango, Celso
AU - Murphy, Declan
N1 - Publisher Copyright:
© 2024
PY - 2024/9
Y1 - 2024/9
N2 - Many individuals with autism spectrum disorder (ASD) experience various degrees of impairment in social interaction and communication, restricted, repetitive behaviours, interests/activities. These impairments make a significant contribution to poorer everyday adaptive functioning. Yet, there are no pharmacological therapies to effectively treat the core symptoms of ASD. Since symptoms of ASD likely emerge from a complex interplay of vulnerabilities, environmental factors and compensatory mechanisms during the early developmental period, pharmacological interventions arguably would have the greatest impact to improve long-term outcomes when implemented at a young age. It is essential therefore, that clinical development programmes of investigational drugs in ASD include the paediatric population early on in clinical trials. Such trials need to offer the prospect of direct benefit (PDB) for participants. In most cases in drug development this prospect is supported by evidence of efficacy in adults. However, the effectiveness of treatment approaches may be age-dependent, so that clinical trials in adults may not provide sufficient evidence for a PDB in children. In this white paper, we consolidate recommendations from regulatory guidelines, as well as advice from the Food and Drug Administration, USA (FDA) and the Committee for Human Medicinal Products (CHMP) consultations on various development programmes on: 1) elements to support a PDB to participants in early paediatric clinical trials in ASD, including single-gene neurodevelopment disorders, 2) aspects of study design to allow for a PDB. This white paper is intended to be complementary to existing regulatory guidelines in guiding industry and academic sponsors in their conduct of early paediatric clinical trials in ASD.
AB - Many individuals with autism spectrum disorder (ASD) experience various degrees of impairment in social interaction and communication, restricted, repetitive behaviours, interests/activities. These impairments make a significant contribution to poorer everyday adaptive functioning. Yet, there are no pharmacological therapies to effectively treat the core symptoms of ASD. Since symptoms of ASD likely emerge from a complex interplay of vulnerabilities, environmental factors and compensatory mechanisms during the early developmental period, pharmacological interventions arguably would have the greatest impact to improve long-term outcomes when implemented at a young age. It is essential therefore, that clinical development programmes of investigational drugs in ASD include the paediatric population early on in clinical trials. Such trials need to offer the prospect of direct benefit (PDB) for participants. In most cases in drug development this prospect is supported by evidence of efficacy in adults. However, the effectiveness of treatment approaches may be age-dependent, so that clinical trials in adults may not provide sufficient evidence for a PDB in children. In this white paper, we consolidate recommendations from regulatory guidelines, as well as advice from the Food and Drug Administration, USA (FDA) and the Committee for Human Medicinal Products (CHMP) consultations on various development programmes on: 1) elements to support a PDB to participants in early paediatric clinical trials in ASD, including single-gene neurodevelopment disorders, 2) aspects of study design to allow for a PDB. This white paper is intended to be complementary to existing regulatory guidelines in guiding industry and academic sponsors in their conduct of early paediatric clinical trials in ASD.
KW - Autism
KW - Clinical trials
KW - Drug development
KW - Paediatrics
UR - http://www.scopus.com/inward/record.url?scp=85196639775&partnerID=8YFLogxK
U2 - 10.1016/j.euroneuro.2024.05.011
DO - 10.1016/j.euroneuro.2024.05.011
M3 - Review article
AN - SCOPUS:85196639775
SN - 0924-977X
VL - 86
SP - 35
EP - 42
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
ER -