JMIR Publications

ABSTRACT

Background:

More sensitive and less burdensome efficacy endpoints are urgently needed to improve the effectiveness of clinical drug development in Alzheimer’s disease (AD). Whereas conventional endpoints lack sensitivity, digital technologies hold promise to amplify detection of treatment signals and capture cognitive anomalies at earlier disease stage. Using digital technologies and combining several test modalities allows for collection of richer information about cognitive and functional status not ascertainable by conventional paper and pencil tests.

Objective:

With the rapid surge of novel sensor technologies entering the field of neuroscience drug development, rigorous methodology studies to assess psychometric properties, operational feasibility and patient acceptance are warranted to accelerate their application in clinical trials.

Methods:

The “Method for Evaluating Digital endpoints In Alzheimer's disease” (MEDIA) study is an exploratory, cross-sectional, non-interventional study to evaluate ten digital technologies in their ability to accurately classify participants into four cohorts according to severity of cognitive impairment and dementia. Moreover, this study assesses psychometric properties of each of the digital technologies tested including: acceptable range – to assess ceiling and floor effects; concurrent validity - to correlate digital outcome measures to traditional paper and pencil tests in AD; reliability - to compare test and re-test; and responsiveness - to evaluate the sensitivity to change in a mild cognitive challenge model. This study included 50 eligible male and female participants (aged 60 to 80 years, inclusive); 13 amyloid-negative cognitively healthy participants (controls), 12 amyloid-positive cognitively healthy participants (pre-symptomatic), 13 participants with Mild Cognitive Impairment (MCI, pre-dementia) and 12 participants with mild AD (mild-dementia). The study involved four in-clinic visits. During the initial visit, participants completed all conventional paper and pencil assessments. During, the three following visits participants underwent a series of novel digital assessments.

Results:

Participant recruitment and data collection began in June 2020 and ran through June 2021. Hence, the data collection occurred during the COVID-19 pandemic (SARS-CoV-2 virus pandemic). Data was successfully collected from all digital technologies to evaluate statistical and operational performance and patient acceptance. This paper reports baseline demographics and characteristics of the population studied as well as study progress during the pandemic. Statistical analysis is ongoing and will not be reported here.

Conclusions:

This study was designed to generate feasibility insights and validation data to help advance novel digital technologies in clinical drug development. Learnings from this study will help guide future methods for assessing novel digital technologies and inform clinical drug trials in early AD aiming to enhance clinical endpoint strategies with digital technologies. Clinical Trial: National Bioethics Committee (NBC reference number VSN-20-022) in Reykjavik, Iceland