A Study of Regulatory Challenges of Pediatric Oncology Phase I/II Trial Submissions and Guidance on Protocol Development.
Journal
Clinical pharmacology and therapeutics
ISSN: 1532-6535
Titre abrégé: Clin Pharmacol Ther
Pays: United States
ID NLM: 0372741
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
30
03
2021
accepted:
20
05
2021
pubmed:
30
5
2021
medline:
12
10
2021
entrez:
29
5
2021
Statut:
ppublish
Résumé
The purpose of this study was to identify key deficiencies in pediatric oncology early phase clinical trial protocols in Germany and to provide guidance for efficient trial protocol development. A systematic review of the response letters of German competent authorities (CAs) and Ethics Committees to phase I/II pediatric oncology trial submissions in the period from 2014 to 2019 was performed. Documents were requested from all five Society for Paediatric Oncology and Haematology in Germany (GPOH) phase I/II trial networks plus all nine German Innovative Therapies for Children with Consortium Cancer (ITCC) centers. A blinded dataset containing aggregated data from 33 studies was analyzed for validation. All deficiencies were reviewed, listed, and weighted using a structured matrix according to frequency, category, significance, and feasibility. In total, documents of 17 trials from 6 different sites were collected. Two hundred fifty deficiencies identified by the CAs were identified and categorized into eight categories. "Toxicity and safety" was the most prominent category (27.6%), followed by "Manufacturing and Import" (18%). The majority of deficiencies were categorized as minor and potential measures as easy to address, but an important group of major and difficult to implement deficiencies was also identified. The blinded validation dataset confirmed these findings. The majority of the EC deficiencies could be resolved by changing the wording in the patient-facing documents. In conclusion, this study was able to detect a pattern of key deficiencies. Most of the shortcomings can be anticipated by minor changes in the protocol and increased awareness can prevent time-consuming revisions, withdrawals, or even rejections. A corresponding guideline describing key regulatory aspects is provided.
Substances chimiques
Antineoplastic Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1025-1037Informations de copyright
© 2021 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
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