ALS-Go-Digital Collaboration

Clinical trials for rare disease that require travel to sites are not patient-friendly, are incredibly inefficient to set up and have a measurable environmental impact.

According to the Centers for Disease Control and Prevention (CDC), as of 2017, it is estimated that there are over 31,000 people living with ALS in the United States. On average, 5,000 new patients are diagnosed every year with this disease.  ALS, or amyotrophic lateral sclerosis, is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. Although there is no cure for this fatal disease, monitoring the progression of ALS over time is a crucial element of clinical care and disease management leading to, on average, clinic visits every three months.  At the same time, clinical trials are necessary to find more effective treatments for this neuromuscular rare disease, but patients often live far from clinical trial sites necessitating long car trips or air travel. Although many factors can contribute to the inability to participant in trials, limited mobility, and inability to travel may be one reason why only 10% of ALS patients participate in studies (Mehta et al, 2021).

In addition, trials designed to collect in-person data from participants require that a site agreement and Institutional Review Board (IRB) approval be in place for each participating site.  A 2013 examination of over 50 ALS studies showed that this process is incredibly inefficient, with an average time to negotiate a site visit and receive IRB approval to be 105 and 125 days, respectively (Atassi et al, 2013).    

Finally, while clinical trials are the last and likely only hope for people living with this rare disease, those trials can have a very significant negative impact on the environment. In the fourteen years since the Sustainable Clinical Trials Group concluded that “clinical trials contribute substantially to greenhouse gas emissions,” notably through energy use in research premises and air travel, little has changed. A recent study estimates that the emissions attributed to the over 350,000 national and international trials are equivalent to 27.5 million tons of GHG emissions (Richie et al, 2020).  There are currently 110 active interventional trials for ALS listed on Clinicaltrials.gov, which fully recruited would require over 13,000 participants.  The Mass General Healey ALS Platform trial requires 7 in-person visits for each enrollee and this is likely typical of most ALS interventional clinical trials, leading to an estimate of 91,000 miles roundtrip in-person visits for participants in all active ALS interventional studies.

The ALS-Go-Digital (ALS GO DIGITAL) Study is a collaborative de-centralized study partnered by Mitsubishi Tanabe Pharma America (MTPA) and the Muscular Dystrophy Association (MDA) that will pair digital data collected remotely with data being collected at participants’ regularly scheduled care visits through the MDA neuroMuscular ObserVational Research hub (MOVR).  By repurposing MOVR data for this study instead of requiring additional clinic visits, approximately three additional in-person visits per participant can be eliminated, preventing an estimated 7 metric tons of CO2 emissions.  Further, this project lays the groundwork, ultimately, to help validate and increase acceptance of outcomes for fully remote, de-centralized ALS clinical trials that may require little to no travel on the part of the participant in the future.

Specifically, the ALS GO DIGITAL study will assess the feasibility of collecting digital health data from ALS patients at home, such as wearable devices and smartphone apps, to assess natural changes of ALS progression over a period of 12 months.  We know from analyzing current MOVR data from over 2,000 ALS participants that ALS MOVR participants are seen in-person at the clinic for routine care about every three months. The ALS Go Digital study will leverage this MOVR data to understand how the remote digital health outcomes relate to the assessments normally collected at clinical research sites.

The study will recruit current MOVR ALS participants who are already contributing data from regular care visits to MDA’s MOVR database. MOVR sites with ALS patients who potentially meet eligibility criteria will be referred to take part in the ALS GO DIGITAL study, where they (upon consent) will be remotely monitored over a period of one year using the following remote data collection methods:   

• A Fitbit Smartwatch for monitoring daytime physical activity and sleep patterns.
• A proprietary smartphone app (ALS HANDs developed by MTPA) for assessing fine motor function of the hands and fingers. 
• An app-based eCOA platform for tracking ALS symptoms using self-reported gold-standard ALS assessments.

By augmenting the study with MOVR data, we will eliminate approximately 210 extra clinic visits by participants to collect that data as part of the study, which amounts to roughly 7 metric tons of CO2 emissions (Based on a 2018 study conducted by MDA with 3000 people responding, the majority live within 1 hour (est. 90-mile round trip) of a care center.  Substituting MOVR data for 3 in-person visits in a 70-person study decreases miles driven by 18,900.  Estimating average gas mileage at 26 miles/gallon and calculating 8,887 grams C02/gallon = ~7 metric tons CO2). 

This pilot study will demonstrate the feasibility of pairing MOVR registry data with remote-collected data, decreasing the number of in-person visits and the environmental footprint of the pilot study, and potentially paving the way for the acceptance of fully remote studies in many rare diseases, with even greater impact on the environmental footprint of rare disease studies.

By repurposing data collected by MOVR during clinic visits that are part of regular care for an ALS patient with activity monitoring data collected remotely, we are:

• saving participants the time and energy that would be required to travel for additional study-specific, in-person visits on top of their regularly scheduled clinic visits
• saving the time required to negotiate individual site agreements for the data collection since agreements and IRB approvals are already in place with MOVR sites and participants have been consented in such a way that their data can be used for this purpose
• potentially reducing the environmental impact of approximately 210 roundtrips by car (70 participants x three visits) to sites for in-person visits

The results of this study will help lead to the development and validation of objective home-based digital measures that are likely to be more sensitive and representative of ALS progression compared to traditional assessments in the clinic. If successful, this approach will empower patients to obtain their own measurements at home while reducing the burden of frequent visits to the clinic. This approach can also free trial recruitment from geographical constraints, potentially leading to more diverse participants (Goodson et al, 2022).

Muscular Dystrophy Association (MDA) is the #1 voluntary health organization in the United States for people living with muscular dystrophy, ALS, and over 300 related rare neuromuscular diseases. For over 70 years, MDA has led the way in accelerating research, advancing care, and advocating for the support of our families. MDA’s mission is to empower the people we serve to live longer, more independent lives.

About 10 years ago, MDA recognized that there was a significant shortage of clinical data in the neuromuscular disease space and started crafting strategic approaches to accelerate data collection and its use by researchers, clinicians, and drug developers.

One strategy that was identified was to leverage the MDA Care Center Network, which is composed of 150 Care Centers, and 2,400 clinical providers across the US. These centers conduct over 90,000 medical visits for over 60,000 individuals annually. In 2013, MDA began capturing data across the MDA Care Center Network to provide valuable knowledge on disease progression for drug development as well as for Real World Data and Real-World Evidence in regulatory submissions and post-approval processes. 

The demonstrated success and value of the pilot registry begun in 2013 fueled the launch of MOVR in 2019 with an updated data collection platform that allows for easier data entry and in-line data validations. MOVR now includes data from 4,000 participants in seven indications across 54 sites. By collaborating with the MT Pharma ALS Go Digital study, we will recruit MOVR participants and combine longitudinal clinical data with remote-collected activity data.  If this pilot is successful, we will have the capability to expand the model to studies in other neuromuscular disease areas including Duchenne and Becker muscular dystrophy, spinal muscular atrophy, limb-girdle muscular dystrophy, facioscapulohumeral muscular dystrophy and Pompe disease.

This is a PROTOTYPE soon to be a PILOT. This collaboration is under contract and scheduled to enroll first participants in August of 2023. The following activities have been completed to date: 

• Execution of the contract between MDA and MTHA to recruit MOVR participants and use MOVR data in the study
• Finalization of the study protocol
  • The study aims to recruit 70 participants.
  • In this fully remote study participants will be monitored using a variety of remote methods powered by digital technology including: A Fitbit Sense2 Smartwatch for monitoring daytime activity, a proprietary mobile app for assessing fine motor function and an app-based eCOA platform for tracking ALS symptoms using self-reported gold-standard ALS assessments.
  • MOVR participants diagnosed with ALS from selected MDA Care Centers will be referred to this study and upon acceptance their existing MOVR data paired with the remote data generated from this study. The study is open to either existing or newly enrolled participants in the MOVR study. Potential participants interested in learning more about the ALS GO DIGITAL study will be directed to the Curebase landing page.
• Selection and execution of a contract with the clinical research organization that will conduct the study
  • The study will be managed by Curebase- a Clinical Research Organization (CRO) with specialized software platform built for decentralized trials. The CRO will work in tandem with designated personnel at MDA to coordinate the logistical aspects and clinical operation activities supporting study enrollment.
• Selection of a study principal investigator and additional ALS experts as study advisors
• Recruitment documents drafted to submit for Institutional Review Board approval
• Presentation of the collaboration plan at the Digital Health Innovation Summit in San Francisco on June 7th

The cost of maintaining the MOVR database, which encompasses 54 active sites and collects data on seven indications, including ALS, is significant.  Sites are compensated for entering data from the medical records as people are seen for their routine care and regular fees for Institutional Review Boards and onboarding new sites are incurred.  Two vendors are also required to host the database itself and the data visualization platform.  As the MOVR database becomes more widely used in projects like the one discussed here, the positive impact will help offset the costs, but we are currently in a bootstrapping stage. MOVR’s continued ability to collect data from clinic visits is threatened by the time and cost of manual data entry by site staff; MOVR staff have been investigating the potential for: 

• Embedding case reports forms directly in Electronic Medical Records 
• Moving to a de-centralized model in which patients are consented directly and their regular care data abstracted from their medical records at a central location
• Pulling data directly from Electronic Medical Records by mapping the data at each center to the MOVR case report forms

Any solution implemented will have an additional cost in the short-term, but the results of solving this problem include MOVR becoming self-sustaining and allow it to scale more rapidly to encompass all 150 Care Centers in MDA’s network and add additional rare diseases. We are also currently limited in how many collaborative projects like the ALS GO DIGITAL study we can run in parallel due to staffing constraints.  

Dr. Hesterlee is the Chief Research Officer of the Muscular Dystrophy Association.  She has over twenty years of experience in neuromuscular research in both the nonprofit and industry space.  She has served as head of research for Parent Project Muscular Dystrophy, the Myotonic Dystrophy Foundation, the Association for Frontotemporal Degeneration, and the Muscular Dystrophy Association’s MDA Venture Philanthropy.  Dr. Hesterlee has also served as project lead for rare disease gene therapy programs at Pfizer, Inc; as Chief Executive Officer of Lion Therapeutics, a special purpose entity of Askbio, Inc.; and as Executive Vice President Portfolio Development at Askbio Inc. 

She has been involved in numerous efforts to remove barriers to therapy development for rare disease and foster interactions between patient advocacy groups and industry. Dr. Hesterlee has served on the governing board of the Health Research Alliance, the NINDS Council, and the Department of Health and Human Service's Muscular Dystrophy Coordinating Committee. She currently chairs the Congressionally Directed Medical Research Program’s Duchenne Muscular Dystrophy Programmatic Review Panel. She received her Ph.D. in neuroscience from the University of Arizona in 1999.

Typically, any data collected for a research study at a clinical site requires a separate site agreement and Institutional Review Board approval for each site (although central IRBs can be used sometimes sites insist on a parallel process through their own IRBs).  Using MOVR clinical data to augment data collected in remote de-centralized studies (studies that are not organized through specific sites) saves the need to put all of those site agreements and IRB approvals in place.  It also dramatically reduces the burden on participants as they need do nothing more than see their doctor on whatever regular schedule they have been keeping for clinical care. 

MOVR happens to be in a unique position to supply this clinical data because the participants have all been consented in such a way that their data can be shared (in accordance with the MDA data sharing requirements) and the data can be collected contemporaneously with other ongoing studies.  This makes repurposing the data very easy and can serve as a model that we can use to augment data augment de-centralized remote studies in other rare diseases.  It may also be a source of return-on-investment for MOVR as industry partners pay fees to use MOVR data in this fashion for their studies.

Over the next five years, we hope to eliminate the need for any remote digital studies in ALS to require additional in-person visits by making the availability of MOVR data for this purpose widely known.

We also seek to expand the use of MOVR data in remote data studies to the other six indications that are part of MOVR.

Finally, we would like to see at least one digital remote outcome for ALS used as a primary outcome for a therapeutic study.

We will measure progress toward the three goals listed above by:

• Monitoring the number of remote ALS studies reported on clinicaltrials.gov to determine if any are still requiring separate in-person visits (will likely require follow-up with study sponsor for specific information); we can also calculate aggregate reduction in carbon footprint for studies that do use MOVR data.
• Documenting the number of remote studies that have used MOVR data in other indications covered in the database.
• Noting the primary outcomes used for ALS clinical trials, as documented on Clinicaltrials.gov or by various news and meeting sources used commonly by our organization.

Digital remote outcomes collected through de-centralized studies have the potential to revolutionize how clinical trials are conducted in this country.  Although they are currently commonly used to collect natural history of disease progression, remotely collected data is less commonly used in drug approvals because many of these outcomes have not been sufficiently validated.  The process of validating a remote outcome typically involves comparing how data collected remotely relates to already validated site-collected outcomes.  For example, in the case of ALS, the ALS Functional Rating Scale (ALSFRS), which consists of a series of observations that are typically scored by medical staff at an in-person visit, is an accepted endpoint for an ALS therapeutic trial.  The ALS GO DIGITAL study will test whether the scores from the ALSFRS completed by study participants on their mobile devices are consistent with those obtained in a clinical setting.

Because this process of validating remote endpoints often requires pairing data collected remotely with validated in-person data, in-person site visits are needed even for what is ostensibly a remote data study.  Using the MOVR data to substitute for the in-person visits in this pilot is a creative way to eliminate these extra visits and could be used any time standard clinical data is needed to augment a remote study.  Eventually, with enough of these kinds of comparative studies, the remote outcomes may be validated for use in therapeutic trials, which would save both time and money, reduce the impact on the environment from in-person visits, and allow clinical trials to recruit from geographically diverse areas.   

MOVR currently collects data in seven indications: amyotrophic lateral sclerosis (ALS), Duchenne muscular dystrophy, Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy, Pompe disease and spinal muscular atrophy.  This model of pairing the MOVR clinical data with remote data could be expanded to all of these disease areas to help validate remote outcomes.

On the MDA side, the MOVR database uses a multi-system approach for data collection, processing, and analysis.  Data is entered at each participating MOVR site by clinical staff into electronic case report forms and retained in a central repository. Data is then de-identified and stored as a limited dataset. MOVR host IQVIA provides a secure PHI (Protected Health Information) data environment and is responsible for data processing and quality control, standardization, and exporting.  The MOVR database is HIPAA and FAIR data principles compliant. 

On the MT Pharma side, the following digital technologies will be used for monitoring participants:

• A Fitbit Sense2 Smartwatch for monitoring daytime physical activity and sleep patterns.
• A proprietary mobile app (ALS HANDs developed by MTPA) for assessing fine motor function of the hands and fingers.
• An app-based eCOA platform (by Curebase) for tracking ALS symptoms using self-reported gold-standard ALS assessments

One full-time employee (Clinical Operations Director) currently assigned to MOVR, with work overseen by Chief Research Officer.  We are in the process of hiring a Data Analytics Director.

This project has been in the works for close to two years now because it took us a bit of time to come up with the current solution of making the trial remote and de-centralized so that access to MOVR data did not require new site agreements with every participating site.  Now that we have the template for making this work, we hope to put together subsequent study collaborations in a matter of months.

Our MOVR team is very small (two people) and currently all female Caucasian.  The Muscular Dystrophy Association as a whole, however, is committed to increasing diversity and representation within its staff (MDA Makes Strides in DEI - Quest | Muscular Dystrophy Association (mdaquest.org)).  In 2021, MDA launched a partnership with Inclusively, a technology-powered platform designed for job seekers with disabilities.  In addition, MDA just launched a summer research internship for diverse undergraduates at four institutions (underway but not yet announced).  Finally, the solution put forth here may make recruitment of more diverse subjects in ALS trials possible by eliminating in-person visits and some geographic barriers.

MOVR is a not-for-profit clinical data hub that leverages MDA’s long-standing relationships with sites in its Care Center Network to collect patient data at point of care.  The aggregate de-identified data are made available at no cost to the sites that do the data collection and to external academic investigators, in compliance with MOVR’s data use agreement.  

For-profit companies pay a fee to access MOVR data, which helps to offset costs.  These companies use MOVR data to aid recruitment, to plan study eligibility requirements, and for regulatory filings. 

In the case of the ALS Go Digital study, an agreement was signed with MT Pharma, who will compensate MDA for time required to recruit study subjects and for access to the MOVR ALS data associated with study participants.

MOVR charges for-profit companies for access to data or for services requiring MOVR data, like targeted recruitment.  To date this income has been relatively small (<10% of operating costs); the remainder is supported through internal budgets of the Association as a core mission activity.  We are in the process of investing in better data analysis tools for our industry partners and to this end are entering into a revenue sharing agreement with the vendor who supplies the MOVR visualization and reporting platform.  We are actively promoting use of MOVR data to industry and believe that the success of the ALS Go Digital study will lead to additional such paying partnerships with companies conducting remote digital studies who also need clinic-entered data.  The financial goal for MOVR is to make it fully self-sustaining through fees to industry data users.

To date, we have generated revenue from biotech and pharma companies for clinical trial recruitment, for study feasibility analyses and for regulatory submissions.  We are also generating income from our pharma partner for the ALS Go Digital Study.