Using Digital Tools to Advance Alzheimer’s Drug Trials During a Pandemic: The EU/US CTAD Task Force

Abstract

The 2020 COVID-19 pandemic has disrupted Alzheimer’s disease (AD) clinical studies worldwide. Digital technologies may help minimize disruptions by enabling remote assessment of subtle cognitive and functional changes over the course of the disease. The EU/US Clinical Trials in Alzheimer’s Disease (CTAD) Task Force met virtually in November 2020 to explore the opportunities and challenges associated with the use of digital technologies in AD clinical research. While recognizing the potential of digital tools to accelerate clinical trials, improve the engagement of diverse populations, capture clinically meaningful data, and lower costs, questions remain regarding the stability, validity, generalizability, and reproducibility of digital data. Substantial concerns also exist regarding regulatory acceptance and privacy. Nonetheless, the Task Force supported further exploration of digital technologies through collaboration and data sharing, noting the need for standardization of digital readouts. They also concluded that while it may be premature to employ remote assessments for trials of novel experimental medications, remote studies of non-invasive, multi-domain approaches may be feasible at this time.

Monthly At-Home Computerized Cognitive Testing to Detect Diminished Practice Effects in Preclinical Alzheimer's Disease

“…Therefore, besides quantifying the amount of improvement over a fixed time-interval as we did in the current study, it would be interesting to characterize learning curves at an individual level and investigate whether the number of assessments needed to reach one's personal plateau could provide an early marker of learning deficits in preclinical AD. Additionally, since other studies have suggested that PE can already be detected over days (Lim et al, 2020 ) or even over repeated assessments within a single day (Darby et al, 2002 ), it would be interesting to explore the feasibility and predictive ability of defining even more short-term PE (days rather than months) in the context of preclinical AD (Kaye et al, 2021 ; Papp et al, 2021a ).…”

Using Digital Speech Assessments to Detect Early Signs of Cognitive Impairment

“…There is a clear and pressing need for sensitive tools to aid in the detection and monitoring of mild cognitive impairment (MCI) and Alzheimer's disease (AD) (1)(2)(3)(4)(5). Given the prevalence of Alzheimer's disease and the aging populations in many countries (6), it will be essential to have tools to help identify the presence of cognitive impairment relating to MCI and AD that can be deployed frequently, and at scale.…”

A Paradox in Digital Memory Assessment: Increased Sensitivity With Reduced Difficulty

“…First, the study illustrates how it is possible to develop interactive digital tools that despite their novelty remain constrained by modern brain behavior models of memory and neuropsychological models of brain disease ( 1 , 46 ). The results show a process for the identification and optimization of dimensions of performance of digital tools in their intended context of use that utilizes knowledge from experimental psychology, statistics and computer technology and shows a pathway for test optimization conducted using a series of highly controlled experiments ( 3 ). Finally, this study illustrates how optimization of a digital tool for one use in making specific decisions in a target group, may not generalize when the same tool is used in the same group to make different decisions about the same aspect of cognition.…”

“…The importance of digital technology to decision-making in the field of the neuropsychology of Alzheimer's disease (AD) is growing rapidly (1)(2)(3). As both pre-symptomatic and symptomatic AD are characterized most strongly by difficulty with learning and memory, digital tools have been applied to many aspects of the assessment of these functions.…”

“…As both pre-symptomatic and symptomatic AD are characterized most strongly by difficulty with learning and memory, digital tools have been applied to many aspects of the assessment of these functions. For example, digital tools have been developed to provide scoring algorithms and reports for data collected using conventional paper and pencil cognitive tests ( 4 ), to replace the written and graphical material used as the stimuli that constrain the written or spoken responses of patients ( 5 , 6 ), and also to measure the speed of manual responses on such tests ( 3 ). While the common application of digital tools in AD neuropsychological settings has been to replace components of standardized assessment or reporting, other approaches have sought to exploit digital technologies so they do not simply recapitulate the printed-spoken-written approaches of clinical interviews.…”