Precision Functional Assessment for Alzheimer’s disease (PFA‐AD): A pilot study framework

Abstract

Background: Current clinical trial assessment of cognitive function and activities of daily living are based on periodic assessments conducted under controlled clinical conditions using standardized clinical measures. This approach is highly correlated with diagnosis of Alzheimer's but has varied relevance to the personal real-life daily challenges to those living with the disease and to those caring for the patient. A recent noted Alzheimer's Association roundtable discussion on digital technologies, noted that the use of digital technologies in clinical trials is actively encouraged. While the field is still new and not completely validated, the opportunity to embed these tools in clinical trials in parallel with other more traditional measures is needed to move the field forward. This study provides a plan to pilot this approach as a means for building on it for expanded use in clinical trials and potentially as part of patient care management in the future. Alzheimer's disease is personal. Assessment of functional capacity should be too. Our goal is to develop a technology-based tool that will enable real-time assessment of real-life function that really matters for persons with Alzheimer's disease and their caregivers. Objectives: Precision Functional Assessment for Alzheimer's Disease (PFA-AD) in real-time under real-life conditions will enable: 1) identification of key behavioral challenges that are relevant to the person with AD and their caregivers; 2) assessment of therapeutic effect in real time across multiple domains of behavioral function; and 3) innovate clinical trial measures of daily activities by conducting functional assessments that are personalized and relevant to the patient and caregiver. Methods: PFA-AD proof of concept development will be embedded as part of a clinical trial to further develop Allopregnanolone, a first in class regenerative therapeutic for AD with the potential to promote self-renewal and repair. This clinical trial is an intravenous (IV) to intramuscular (IM) formulation bridging study to identifying the IM dose equivalent to a pre-established IV dose (4mg) and assess its safety and tolerability as a weekly injection in 12 persons (6 women and 6 men) diagnosed with AD (https://clinicaltrials. gov/ct2/show/ NCT03748303). MyOwnMed (MOM), Inc has created a 360° digital platform that captures first person patient experience and facilitates better patient engagement, measures clinical treatment efficacy and outcomes from real world patient experiences. The PFA-AD digitally-powered platform will enable AD researchers to: 1) connect and analyze data from the Alzheimer's patients and their caregivers; 2) Create digitally-powered real-world studies to gather real-time, real world data; 3) Integrate data across clinical trial measures to generate predictive indicators of therapeutic impact. Initially, the platform will support simple measures of lifestyle and daily function as defined by the team working with patients and will include surveys to be delivered digitally to both the patient and caregiver using the MOM portal and mobile software. This will allow content to be personalized for each patient/caregiver, while at the same time providing for consistent data capture. Control for survey presentation timing, and determination of lifestyle indicators will be via the study coordinator using the MOM software platform. This will allow for the study team to define key time periods for survey administration, while at the same time capturing daily life data more continuously. Wearable technologies will be integrated to capture physical activity and sleep, using available application interfaces (API's) that will be seamlessly integrated into the MOM mobile application for patients/caregivers. Results: Analysis of PFA-AD data will include: 1) Ease of use; 2) Fidelity of personalized functional profile (did the survey questions measure the function); 3) Correlation of personalized real-life functions with clinical trial standardized cognitive assessments; 4) Correlation of personalized real-life functions with clinical trial MRI-based brain analytics (gray and white matter structure, diffusion tensor imaging for white matter tracks and resting state default mode network as an indicator of synaptic connectivity); 5) Feasibility of scale up for inclusion in Allo Phase 2 clinical trial. Conclusions: Alzheimer's disease is personal, and assessment of function can be too. The PFA-AD application innovates precision analytics to measure cognition and behavior that really matters, in real time, that is personalized to both the person living with Alzheimer's disease and their caregiver. Outcomes of this research will advance precise and personalized analysis of real-life function to assess therapeutic response.