Graphical user interfaces for regulatory‐endorsed quantitative drug development tools in Alzheimer's disease: Human/Trial design. (7th December 2020)

• Record Type: Journal Article
• Authors: Romero, Klaus; Hanan, Nathan J.; Sivakumaran, Sudhir; Sinha, Vikram; Haeberlein, Samantha Budd; Gold, Michael
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 9
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.044029
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Model‐informed drug development (MIDD) can improve cost effectiveness of research and development (R&D) decision‐making. The Critical Path for Alzheimer's Disease (CPAD) Consortium has developed a mild‐to‐moderate Alzheimer's disease clinical trial simulator, which is intended to optimize clinical trial design in this target population, when using ADAS‐Cog as the primary endpoint. This tool represented the first‐ever FDA and EMA‐endorsed quantitative drug development tool. The CPAD team has also developed a pre‐dementia disease progression model, which received an EMA letter of support, as a trial enrichment tool for pre‐dementia trials that use CDR‐SB as the primary endpoint. In order to democratize the use of these tools, graphical user interfaces (GUIs) were developed for these two models. Method: The GUIs were developed using R‐Shiny, focusing on the drug‐disease‐trial model aspects of the clinical trial simulator for mild‐to‐moderate AD, with emphasis on the sources of variability (APOE4, sex, baseline MMSE and age); and focusing on the disease progression predictors of the trial enrichment model for pre‐dementia (baseline MMSE, age and hippocampal volume, APOE4 and sex). Result: The GUIs were beta‐tested by pharmacometricians, statisticians, clinical trialists and clinicians. Their feedback was used to further improve the functionality of the GUIs. Focus was put on the ability of the users to intuitively set up the simulation framework for specific studies, the underlying assumptions, and the graphical and tabular output of simulated results. Conclusion: The publicly accessible GUIs will increase the usability of these quantitative drug development tools. Examples of their application include informing stage‐gate decisions; optimization of study design; patient selection; and sample size estimations.