Conference Posters

Synthetic Control Subjects for Alzheimer's Disease Clinical Trials (JSM 2019)

Charles Fisher, Yannick Pouliot, Aaron Smith, Jonathan Walsh

Objective: To develop a method to model disease progression that simulates detailed clinical data records for subjects in the control arms of Alzheimer's disease clinical trials. Methods: We used a robust data processing framework to build a dataset from a database of subjects in the control arms of a diverse set of 28 clinical trials on Alzheimer's disease. From this dataset, we selected 1908 subjects with 18-month trajectories of 44 variables and trained a probabilistic generative model called a Conditional Restricted Boltzmann Machine (CRBM) to simulate disease progression in 3-month intervals across all variables. Results: Based on a statistical analysis comparing data from actual and simulated subjects, the model generates accurate subject-level distributions across variables and through time. Focusing on a common clinical trial endpoint for Alzheimer’s disease (ADAS-Cog), we show the model can accurately predict disease progression and may be used to model the control arm of a clinical trial whose data are distinct from the training and test datasets. Conclusion: The ability to simulate dozens of clinical characteristics simultaneously is a powerful tool to model disease progression. Such models have useful applications for clinical trials, from analyzing control groups to supplementing actual subject data in control arms.