R01AG084236

Acts (AD Clinical Trial Simulation): Developing Advanced Informatics Approaches for an Alzheimer's Disease Clinical Trial Simulation System - Abstract

Alzheimer's disease and related dementias (AD/ADRD) are the most common neurodegenerative brain diseases and characterized by massive loss of memory and learning. AD/ADRD affects more than 6 million Americans and puts a heavy burden on caregivers in society. However, effective treatment of AD/ADRD is still lacking.

While randomized clinical trials (RCT) can provide reliable evidence on the effectiveness of interventions, they also have inherent limitations including high cost and long execution time. In addition, RCTs usually are conducted on selected populations and in specialized environments with limited follow-up time. Therefore, they could have limitations in generalizability to real-world clinical practice.

Clinical trial simulation is becoming an effective approach to assess feasibility, investigate assumptions, and refine study protocols before conducting the actual trials. Increased availability and granularity of real-world data (RWD) such as electronic health record (EHR) and medical claims data, along with advances in data science, offer untapped opportunities to leverage RWD for trial simulation studies to generate real-world evidence (RWE).

Nevertheless, there are methodological barriers and informatics challenges in supporting RWD-based trial simulation studies, especially for AD: (1) clinical trials need to be represented using a formal and standard approach (i.e., ontologies) to capture the entire scope of a trial, especially eligibility criteria and outcome measures (i.e., both effectiveness and safety); (2) such formal and standard representation needs to be made interoperable with RWD standards (e.g., common data models) to identify study cohorts and relevant, important patient characteristics (i.e., via computable phenotypes and natural language processing [NLP] methods as rich AD-related information such as cognitive scores often exist in unstructured clinical notes); and (3) comprehensive and reusable pipelines need to be implemented that can seamlessly align with existing large-scale RWD for generating high-quality analytic-ready datasets for AD clinical trial simulation studies.

To address these barriers, we propose create and pilot test the ACTS (Alzheimer's Disease Clinical Trial Simulation) system, leveraging three large collections of RWD (~20 million patients from the OneFlorida network, UT Physician Clinical Data Research Warehouse, and the Optum's Clinformatics Data). Specifically, we propose to develop novel informatics approaches to represent the entirety of AD trials while considering the connection of RWD (Aim 1), to use both structured and unstructured RWD to develop robust phenotyping algorithms that will render previously incomputable AD study traits computable (Aim 2), and to develop the ACTS web application, which will provide an integrated environment for AD researchers to construct virtual AD trials using an interactive web interface and obtain analytic-ready datasets for trial simulation studies (Aim 3).

Mayo Clinic Jacksonville (A Nonprofit Corporation)

TO ENCOURAGE BIOMEDICAL, SOCIAL, AND BEHAVIORAL RESEARCH AND RESEARCH TRAINING DIRECTED TOWARD GREATER UNDERSTANDING OF THE AGING PROCESS AND THE DISEASES, SPECIAL PROBLEMS, AND NEEDS OF PEOPLE AS THEY AGE. THE NATIONAL INSTITUTE ON AGING HAS ESTABLISHED PROGRAMS TO PURSUE THESE GOALS. THE DIVISION OF AGING BIOLOGY EMPHASIZES UNDERSTANDING THE BASIC BIOLOGICAL PROCESSES OF AGING. THE DIVISION OF GERIATRICS AND CLINICAL GERONTOLOGY SUPPORTS RESEARCH TO IMPROVE THE ABILITIES OF HEALTH CARE PRACTITIONERS TO RESPOND TO THE DISEASES AND OTHER CLINICAL PROBLEMS OF OLDER PEOPLE. THE DIVISION OF BEHAVIORAL AND SOCIAL RESEARCH SUPPORTS RESEARCH THAT WILL LEAD TO GREATER UNDERSTANDING OF THE SOCIAL, CULTURAL, ECONOMIC AND PSYCHOLOGICAL FACTORS THAT AFFECT BOTH THE PROCESS OF GROWING OLD AND THE PLACE OF OLDER PEOPLE IN SOCIETY. THE DIVISION OF NEUROSCIENCE FOSTERS RESEARCH CONCERNED WITH THE AGE-RELATED CHANGES IN THE NERVOUS SYSTEM AS WELL AS THE RELATED SENSORY, PERCEPTUAL, AND COGNITIVE PROCESSES ASSOCIATED WITH AGING AND HAS A SPECIAL EMPHASIS ON ALZHEIMER'S DISEASE. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.866 - Aging Research

National Institute on Aging (NIA) [HHS - NIH]

Jacksonville, Florida 322241865 United States

Single Zip Code

Early and Late Stage Clinical Trials for the Spectrum of Alzheimers Disease/Alzheimers Related Dementias and Age-Related Cognitive Decline (R01 Clinical Trial Optional) (PAR-21-359)

Amendment Since initial award the total obligations have increased 173% from $1,155,311 to $3,150,520.