DMD Clinical Trial Simulation Tool
This model-based clinical trial simulation platform is aimed at optimizing clinical trial design of efficacy studies of potential therapies for Duchenne muscular dystrophy (DMD).
What is the DMD Clinical Trial Simulation tool?
- A model-based clinical trial simulation tool (CTS) aimed at optimizing clinical trial design of efficacy studies of potential therapies for Duchenne muscular dystrophy (DMD).
- The D-RSC team developed models of the longitudinal changes in the velocity at which individuals can complete specified timed functional tests, frequently used as clinical trial efficacy endpoints (supine-stand, 4-stair climb and 10meter walk/run test or 30-foot walk/run test), as well as the longitudinal changes in forced vital capacity (FVC) and North Star Ambulatory Assessment total score (NSAA).
- The longitudinal models incorporate relevant sources of variability, such as baseline severity at study start, age, steroid use (at baseline or naïve), genetic mutation, study type (clinical trial vs. observational), and race.
- The EMA has issued a Letter of Support to encourage the further development and validation of the DMD Clinical Trial Simulation Platform, as well as encouraging sponsors to share patient-level data with the D-RSC team.
General Information About the DMD Clinical Trial Simulation Tool
The trial simulation tool is intended to inform exploration of key design constructs including:
- Sample size
- Trial arm allocation
- Patient enrollment criteria
- Treatment effect size
- Predictive effect of baseline covariates
Clinical trial simulations based on this model should be considered in the context of additional aspects (e.g., characteristics of the individual population, clinical pharmacology, and safety of potential therapies) and are not intended to replace the execution of actual clinical trials for the assessment of safety and efficacy.
ShinyApp:
For scientists and clinicians, a cloud-based Graphical User Interface (GUI) has been developed, which allows a user-friendly experience to perform simulations based on the model.
For the proper application of this clinical trial simulation tool, the following background expertise and resources are recommended:
- Familiarity with the covered endpoints and disease background
- Familiarity with disease progression modeling and mixed effect models
Guide for Accessing DMD Clinical Trial Simulation (CTS) Tool – ShinyApp
R Package:
This package provides the simulation environment codes of the disease progression model underlying the Shiny App.
Please take time to review the minimum system requirements within the ReadMe file.
For the proper application of this clinical trial simulation tool, the following background expertise and resources are recommended:
- Advanced-level knowledge of the statistical and methodological background behind drug-disease-trial models
- Advanced-level knowledge of the R programming language for statistical analysis
Guide for Accessing DMD Clinical Trial Simulation (CTS) Tool – R Package
D-RSC would like to acknowledge the contributions from the following collaborators:
- Varun Aggarwal (Takeda)
- Jackson Burton (Biogen)
- Daniela J. Conrado (Zentalis Pharmaceuticals)
- Diane Corey (C-Path)
- Zihan Cui (C-Path)
- Sarah Kim (University of Florida)
- Jane Larkindale (PepGen)
- Karthik Lingineni (Novartis)
- Shu Chin Ma (C-Path)
- Juan Francisco Morales (C-Path)
- Klaus Romero (C-Path)
- Stephan Schmidt (University of Florida)
- Lauren Quinlan (C-Path)
- Jordan M. Wilk (University of Florida)
- Deok Yong Yoon (Novartis)
- Yi Zhang (C-Path)
Lingineni, K., et al. on behalf of the Cooperative International Neuromuscular Research Group investigators and Duchenne Regulatory Science Consortium members (2022). Development of a model-based clinical trial simulation platform to optimize the design of clinical trials for Duchenne muscular dystrophy. CPT: Pharmacometrics & Systems Pharmacology, 11(3), 318-332. https://doi.org/10.1002/psp4.12753