An Ecologically Valid, Longitudinal, and Unbiased Assessment of Treatment Efficacy in Alzheimer Disease (the EVALUATE-AD Trial): Proof-of-Concept Study.

Neil William Douglas Thomas,Hiroko Dodge,Jennifer Marcoe,Nicole Sharma,Jeffrey Kaye,Zachary Beattie,Katherine Wild,Kirsten Wright,Nora Mattek

doi:10.2196/17603

Abstract

BackgroundThe current clinical trial assessment methodology relies on a combination of self-report measures, cognitive and physical function tests, and biomarkers. This methodology is limited by recall bias and recency effects in self-reporting and by assessments that are brief, episodic, and clinic based. Continuous monitoring of ecologically valid measures of cognition and daily functioning in the community may provide a more sensitive method to detect subtle, progressive changes in patients with cognitive impairment and dementia.ObjectiveThis study aimed to present an alternative trial approach using a home-based sensing and computing system to detect changes related to common treatments employed in Alzheimer disease (AD). This paper introduces an ongoing study that aims to determine the feasibility of capturing sensor-based data at home and to compare the sensor-based outcomes with conventional outcomes. We describe the methodology used in the assessment protocol and present preliminary results of feasibility measures and examples of data related to medication-taking behavior, activity levels, and sleep.MethodsThe EVALUATE-AD (Ecologically Valid, Ambient, Longitudinal and Unbiased Assessment of Treatment Efficacy in Alzheimer’s Disease) trial is a longitudinal naturalistic observational cohort study recruiting 30 patients and 30 spouse coresident care partners. Participants are monitored continuously using a home-based sensing and computing system for up to 24 months. Outcome measures of the automated system are compared with conventional clinical outcome measures in AD. Acceptance of the home system and protocol are assessed by rates of dropout and protocol adherence. After completion of the study monitoring period, a composite model using multiple functional outcome measures will be created that represents a behavioral-activity signature of initiating or discontinuing AD-related medications, such as cholinesterase inhibitors, memantine, or antidepressants.ResultsThe home-based sensing and computing system has been well accepted by individuals with cognitive impairment and their care partners. Participants showed good adherence to the completion of a weekly web-based health survey. Daily activity, medication adherence, and total time in bed could be derived from algorithms using data from the sensing and computing system. The mean monitoring time for current participants was 14.6 months. Medication adherence, as measured with an electronic pillbox, was 77% for participants taking AD-related medications.ConclusionsContinuous, home-based assessment provides a novel approach to test the impact of new or existing dementia treatments generating objective, clinically meaningful measures related to cognition and everyday functioning. Combining this approach with the current clinical trial methodology may ultimately reduce trial durations, sample size needs, and reliance on a clinic-based assessment.International Registered Report Identifier (IRRID)DERR1-10.2196/17603

Highlights

BackgroundThe current clinical trial methodology for testing dementia treatments relies on the time-honored approach of assessing enrolled individuals with a combination of self-report measures, cognitive and physical function tests, and biomarkers
Continuous, home-based assessment provides a novel approach to test the impact of new or existing dementia treatments generating objective, clinically meaningful measures related to cognition and everyday functioning
Recency effects are a particular concern, considering that people tend to report what they most recently experienced in the last few days as opposed to the overall quality of change for the entire period or may forget events which occurred during the period closest to the last visit

Summary

Introduction

The current clinical trial methodology for testing dementia treatments relies on the time-honored approach of assessing enrolled individuals with a combination of self-report measures (eg, function, mood, adverse events), cognitive and physical function tests (eg, psychometric batteries, timed walks), and biomarkers (eg, neuroimaging-, cerebrospinal fluid-, plasma-based). These measures are typically collected at a baseline visit, followed by randomization of patients to a placebo or treatment arm. Continuous monitoring of ecologically valid measures of cognition and daily functioning in the community may provide a more sensitive method to detect subtle, progressive changes in patients with cognitive impairment and dementia

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