Digital Technology in Clinical Trials for Multiple Sclerosis: Systematic Review

Abstract

Clinical trials in multiple sclerosis (MS) have been including digital technology tools to overcome limitations in treatment delivery and disease monitoring. In March 2020, we conducted a systematic search on pubmed.gov and clinicaltrials.gov databases (with no restrictions) to identify all relevant published and unpublished clinical trials, in English language, including MS patients, in which digital technology was applied. We used “multiple sclerosis” and “clinical trial” as the main search words, and “app”, “digital”, “electronic”, “internet” and “mobile” as additional search words, separately. Digital technology is part of clinical trial interventions to deliver psychotherapy and motor rehabilitation, with exergames, e-training, and robot-assisted exercises. Digital technology has been used to standardise previously existing outcome measures, with automatic acquisitions, reduced inconsistencies, and improved detection of symptoms (e.g., electronic recording of motor performance). Other clinical trials have been using digital technology for monitoring symptoms that would be otherwise difficult to detect (e.g., fatigue, balance), for measuring treatment adherence and side effects, and for self-assessment purposes. Collection of outcome measures is progressively shifting from paper-based on site, to internet-based on site, and, in the future, to internet-based at home, with the detection of clinical and treatment features that would have remained otherwise invisible. Similarly, remote interventions provide new possibilities of motor and cognitive rehabilitation.

The Feasibility of a Web-Based Educational Lifestyle Program for People With Multiple Sclerosis: A Randomized Controlled Trial

“…Further, people with MS access online information and use the internet for healthcare reasons at high rates, suggesting that online supports for self-management are valued by this population ( 38 – 40 ). Digital health interventions have shown efficacy in assisting people with MS in making lifestyle changes likely to benefit overall health ( 17 – 19 , 41 – 43 ). The present study builds on existing work on digital health for people with MS and provides additional insight into factors that affect user engagement and participation with DHIs.…”

Decentralised clinical trials in multiple sclerosis research

“…There is a risk that people who prefer in-person interactions or are unable to use digital technologies-for example, due to technological illiteracy, physical disabilities, cognitive or visual problems, or lack of resources to support the use of such technologies (e.g., high-speed internet connections), may still be excluded from DCTs. 38,39 Advancements in technologies may enhance the usability of digital tools for certain populations. In some circumstances, willing friends or family members could be trained to assist participants with completion of their trial activities remotely.…”

“…Several existing outcome measures are being or have been converted into tele-or digital assessments to enable remote monitoring of participants and providing them with flexibility in timing their research activities (e.g., the Expanded Disability Status Scale or the Multiple Sclerosis Functional Composite). 39,44,45 This approach allows for more frequent and even continuous assessments (as opposed to infrequent in-person study visits which tend to be restricted by time), leading to increased power of a study.…”

“…49 The digital era has also unlocked opportunities to develop new outcome measures or to assess additional aspects of participants' performance when using existing ones. 38,39 Portable and wearable devices, such as smartphones and smartwatches, enable measurement of participants' physical activity through both passive monitoring and active instructed tests, 28,39,48 and their use appears to be acceptable to people with MS. 28 These technologies not only capture conventional measures of physical disability in MS, such as mobility or dexterity, but also introduce objective measurements of other aspects of physical health, such as falls, fatigue, sleep, and autonomic dysfunction, which commonly affect the quality of life of people with MS but can be invisible or difficult to capture in conventional RCTs. 39,48 The application of wearable sensors, however, goes beyond the quantification of physical and physiological features and is also being considered for measuring biomarkers in bodily fluids.…”

Developing a Digital Solution for Remote Assessment in Multiple Sclerosis: From Concept to Software as a Medical Device

“…Many of these tools are non-regulated wellness applications designed to support day-to-day disease management, for example through symptom or medication intake tracking, visit-scheduling, provision of disease education, and connectivity to supportive care facilities or patient social media networks [ 18 , 19 , 20 , 21 , 22 , 23 ]. Other smartphone-based solutions enable assessment of functional parameters affected by the disease, such as mobility and cognition, or therapeutic benefit, such as for fatigue or depression [ 24 ]. Data and digital biomarkers collected by patient-facing apps may provide clinical value by generating new insights into the MS disease course, ultimately improving the understanding of individual disease trajectories and response to intervention.…”