Pathway for Development and Validation of Multi-domain Endpoints for Amyloid Light Chain (AL) Amyloidosis.
AL amyloidosis
Clinical trial
Multi-domain endpoints
Public–private partnership
Rare diseases
Statistical validation
Journal
Therapeutic innovation & regulatory science
ISSN: 2168-4804
Titre abrégé: Ther Innov Regul Sci
Pays: Switzerland
ID NLM: 101597411
Informations de publication
Date de publication:
17 Apr 2024
17 Apr 2024
Historique:
received:
28
07
2023
accepted:
08
03
2024
medline:
18
4
2024
pubmed:
18
4
2024
entrez:
17
4
2024
Statut:
aheadofprint
Résumé
Immunoglobin light chain (AL) amyloidosis is a rare disease in which a plasma cell dyscrasia leads to deposition of insoluble amyloid fibrils in multiple organs. To facilitate development of new therapies for this heterogenous disease, a public-private partnership was formed between the nonprofit Amyloidosis Research Consortium and the US Food and Drug Administration Center for Drug Evaluation and Research. In 2020, the Amyloidosis Forum launched an initiative to identify clinical trial endpoints and analytic strategies across affected organ systems and life impacts via specialized working groups. This review summarizes the proceedings of the Statistical Group and proposes a pathway for development and validation of multi-domain endpoints (MDEs) for potential use in AL amyloidosis clinical trials. Specifically, drawing on candidate domain-specific endpoints recommended by each organ-specific working group, different approaches to constructing MDEs were considered. Future studies were identified to assess the validity, meaningfulness and performance of MDEs through use of natural history and clinical trial data. Ultimately, for drug development, the context of use in a regulatory evaluation, the specific patient population, and the investigational therapeutic mechanism should drive selection of appropriate endpoints. MDEs for AL amyloidosis, once developed and validated, will provide important options for advancing patient-focused drug development in this multi-system disease.
Identifiants
pubmed: 38632158
doi: 10.1007/s43441-024-00641-6
pii: 10.1007/s43441-024-00641-6
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s).
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