Interim decision making in seamless trial designs: An application in an adaptive dose-finding study in a rare kidney disease.
IgA nephropathy
adaptive designs
data monitoring committee
dose-finding
proof-of-concept
simulations
Journal
Pharmaceutical statistics
ISSN: 1539-1612
Titre abrégé: Pharm Stat
Pays: England
ID NLM: 101201192
Informations de publication
Date de publication:
11 Sep 2023
11 Sep 2023
Historique:
revised:
30
06
2023
received:
26
01
2023
accepted:
03
08
2023
medline:
11
9
2023
pubmed:
11
9
2023
entrez:
11
9
2023
Statut:
aheadofprint
Résumé
Adaptive seamless trial designs, combining the learning and confirming cycles of drug development in a single trial, have gained popularity in recent years. Adaptations may include dose selection, sample size re-estimation and enrichment of the study population. Despite methodological advances and recognition of the potential efficiency gains such designs offer, their implementation, including how to enable efficient decision making on the adaptations in interim analyzes, remains a key challenge in their adoption. This manuscript uses a case study of an adaptive seamless proof-of-concept (Phase 2a)/dose-finding (Phase 2b) to showcase potential adaptive features that can be implemented in trial designs at earlier development stages and the role of simulations in assessing the design operating characteristics and specifying the decision rules for the adaptations. It further outlines the elements needed to support successful interim analysis decision making on the adaptations while safeguarding study integrity, including the role of different stakeholders, interactive simulation-based tools to facilitate decision making and operational aspects requiring preplanning. The benefits of the adaptive Phase 2a/2b design chosen compared to following the traditional two separate studies (2a and 2b) paradigm are discussed. With careful planning and appreciation of their complexity and components needed for their implementation, seamless adaptive designs have the potential to yield significant savings both in terms of time and resources.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Novartis Pharma AG
Informations de copyright
© 2023 Novartis Pharma AG and The Authors. Pharmaceutical Statistics published by John Wiley & Sons Ltd.
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