Everything you wanted to know about digital clinical trials but didn’t know whom to ask. An interview with Katie Baca-Motes, Co-Founder of Scripps Research Digital Trial Center.
When I hear the term “digital trials,” I think about people entering data on the computer or research kit on smartphones that can also collect data from wearables or in-build sensors. Is this the correct understanding of this area?
There are several terms used in the “digital trials” space—remote trials, site-less trials, direct-to-participant trials, and most commonly, decentralized trials. They all point to the shift we’ve seen in the past several years moving clinical research away from its reliance on traditional academic medical centers (AMCs).
While much of clinical research is still being conducted at AMCs, recent technical advances and policy changes have enabled trials to be largely conducted outside of the traditional brick-and-mortar sites. There are typically several “digital” components to these trials, including electronic consent and signatures and participant-reported outcomes done via surveys delivered electronically to a person’s smartphone or accessed on the web.
Some trials also include remote monitoring of trial participants with wearable sensors, activity trackers and other devices that enable periodic capture of data or continuous monitoring during the trials. Most recently, there has also been a shift toward patient-mediated access to electronic health records and claims data, which allow for trial coordinators to recruit patients outside their specific health care system or health insurance system.
There are often non-digital aspects of decentralized trials as well, including things like biosample capture (blood, saliva, stool samples) which can be collected remotely in the home by the participants themselves or by a healthcare provider coming to the participants’ home. In some cases, participants of decentralized trials will be asked to visit an easily accessible clinic for sample collection or examinations. For example, in the U.S., these places include ubiquitous drugstores like Walgreens or CVS or a Quest clinical lab, allowing for trial activities to take place at one of the thousands of locations.
Having this big picture in mind, let’s get into the details. What are the fascinating digital trials conducted so far in Scripps Research?
In 2016, I was fortunate to meet Dr. Eric Topol and Dr. Steve Steinhubl—they invited me to work with them on one of the very first direct-to-participant digital trials.
This was the mSTOPs trial conducted in partnerships with Janssen Pharmaceuticals (the R&D arm of Johnson & Johnson) and Aetna (a large health insurance company in the U.S, now owned by CVS). Looking back now, that trial would look simplistic compared to what we are currently running. Still, at the time, it was utterly novel—from the digital recruitment of a high-risk elderly patient population, electronic consent, remote monitoring and return of results and outcomes to trial participants.
The mSToPS trial was a precursor for several other studies using a wearable sensor for early detection of atrial fibrillation, such as the J&J/Apple Heartline Study. And, perhaps more importantly, mSToPs broke the mold of how we conduct clinical research, showcasing the possibilities of decentralized trials. It really set the stage for other projects, including standing up The Participant Center for the National Institute of Health’s All of Us Research Program, which is well on its way to its ambitious goals of enrolling and collecting multimodal data on 1M or more diverse individuals living in the United States and using these data to accelerate biomedical research across a number of health conditions.
Those early trials and our incredible collaborations with groups across the country and world have served as a blueprint for the advances we are now seeing in the field.
DETECT was launched in response to COVID-19. The participants are sharing wearable sensor data from fitness trackers and smartwatches along with any symptoms, diagnoses, and vaccinations to help us understand the onset and progression of COVID-19 and to improve surveillance of the disease.
In the maternal health space, we’ve launched PowerMom, which uses remote monitoring and patient-reported outcomes to better understand what contributes to healthy pregnancies and aims to address the maternal mortality crisis in the U.S.
And PROGRESS is our most ambitious digital trial to date, focused on metabolic health. Participants are collecting a wealth of data on themselves—contributing health history data, demographic information, electronic health records, blood, saliva, and stool samples and tracking nutritional intake, activity, sleep and continuous glucose measures over the course of the study.
One of the most exciting aspects to watch is the enthusiasm of the participants as they get individualized, real-time data back throughout the study. It was a pivotal and somewhat controversial decision we made at Scripps to commit to returning information back to our participants. But the experience we’ve had starting with mSToPs and advancing to the robust data visualizations of PROGRESS show the tremendous power of truly engaging participants as partners in the research process.
That’s encouraging when benefits from the study go back to those who collect and donate data. Let me elaborate on The Digital Engagement and Tracking for Early Control and Treatment study in which 40 000 individuals shared their data during the COVID-19 pandemic. The results suggest that wearable devices and mobile apps can be effective tools for monitoring and controlling the spread of infectious diseases. Since we know it, what is the next step to scale up and improve infectious disease surveillance?
The study was launched in response to COVID-19 in early March 2020. The idea for the DETECT was built on the research of two scientists at Scripps Research, Dr. Jennifer Radin and Dr. Giorgio Quer.
Dr. Quer’s team had been examining resting heart rate (RHR) variability between individuals and long- and short-term changes in an individual’s daily RHR, while Dr. Radin had published a retrospective analysis of Fitbit data which found that identifying the proportion of individuals each week with an elevated RHR and sleep significantly improved real-time prediction of flu-like illness activity.
This previous research published in January and February of 2020 inspired our team and collaborators to launch a prospective study during the pandemic to help us understand the onset and progression of COVID-19 and to improve surveillance of the disease.
DETECT—launched with the help of several collaborators, including Fitbit, Walgreens, CVS, and CareEvolution—served as a great example of how digital tools can be leveraged in the fight against COVID-19. Over 40,000 participants partnered with the study to donate wearable sensor data from fitness trackers and smartwatches along with any symptoms, diagnoses, and vaccines. Early findings in Nature Medicine showed that wearable device data can be used in identifying cases of COVID-19 by evaluating changes in heart rate, sleep and activity levels.
The collected data has also been used to study the prolonged physiological changes associated with COVID-19 infection, to further develop improved algorithms that rely on passively collected data only, and to monitor physiological response to vaccines. In addition, the DETECT results have been independently validated by several studies and platforms in the U.S. and internationally.
Most recently, the team, led by Dr. Radin, used the data to showcase how programs like DETECT can contribute to public health disease surveillance programs. A pilot program sponsored by the Rockefeller Foundation showed that passively collected sensor data from consented participants significantly improved the seven-day average predictions by 32.9% in California—as well as by 12.2% in the United States for predictions occurring 12 days in the future.
Several public health surveillance tools have been used during the pandemic, including wastewater, electronic health records, and pharmacy information. Adding sensor data could prove to be a powerful addition to help accurately forecast outbreaks of Covid-19 and other viral illnesses. However, scaling these programs will require government support and coordination.
Government support and coordination are crucial, but we also need people willing to join virtual clinical studies. Do you think people are ready to share—or donate—their data for public good? And how to convince those who are still reluctant or do not trust the institutions that collect the data?
Some people are definitely willing to donate data for public good, as evidenced by programs like DETECT, which quickly enrolled tens of thousands in the first weeks after launch. We also observed it in large-scale programs like the All of Us Research Program, which has over 500,000 participants to date. Other countries have also seen success in recruiting large cohorts of people. For example, Germany’s Robert Koch Institute, a collaborator of Scripps Research, ran a program similar to DETECT, Corona-Datenspende, that had half a million people sharing wearable device data.
That said, there is still much work to be done to build trust and ensure that all communities, especially marginalized communities, have an environment in which they can contribute to and benefit from research designed for public good.
I’m not sure focusing on how to “convince” people is the right question to ask ourselves as we think about how to increase participation. Instead, we need to ask ourselves how to deliberately and thoughtfully build programs that are inclusive, have input and leadership from all populations that are expected to contribute, and have a path toward immediate and long-term benefits to those populations. Additionally, data privacy and security protections must be the top priority for any program collecting individual data.
Digital clinical trials have three indisputable advantages: access to real-time data, cohort size and decentralization, meaning equity and diversity. What else would you add to this list?
I would add speed and cost savings to that list. As technology advances, digital clinical trials will have a significant financial advantage over the more traditional clinical trials and will be able to recruit much more quickly.
Digital trials also provide an opportunity for research to be conducted in a “real world” setting. So much of our knowledge in the past has relied on episodic measures taken in artificial environments. Take sleep research, for example; the limited sleep research that has been done was conducted in a sleep lab with sensors and wires attached to an individual—a far cry from a regular sleep environment. Now, with wearable and passive sensors, we are about to enter a phase where we can do robust sleep research on hundreds of thousands of people in their own environments, which we think will lead to a wealth of knowledge on sleep’s impact on health and behavior.
And what are the risks? And how to minimize them?
I think the biggest risk involving the shift to digital clinical trials is to assume decentralization and access will automatically translate into increased representation and diversity.
This is not one of those “build it and they will come” type of things. Those of us conducting research still need to do the hard work to make research truly accessible, inviting, and trustworthy—that will take significant effort beyond shifting to a digital approach.
The other major risk goes back to what I mentioned previously about data security. People running digital clinical trials need to be diligent about two things: selection of technology partners and the implementation of data transfer protocols to ensure best-in-class data security for participant data; and transparency about risks to participants so they have all the necessary information to understand risks and benefits of sharing their data.
You moved recently from the U.S. to Europe. How different are these two markets when it comes to digital clinical trials? What chances and barriers do you see in the European market?
The E.U. offers a tremendous amount for us to explore. So many of our national partners in the U.S. have a global presence. Expanding the Digital Trials Center to build on strategic partnerships with European companies and institutions is a big part of why I made the move.
In the U.S., for example, we’re seeing increased interest and adoption of the digital clinical trial model by pharmaceutical companies. We’re interested in helping them navigate this transition and having two markets to choose from will broaden the opportunities. Clearly, there will be differences, whether in the regulatory bodies involved or even just in how digital trials are defined. All exciting and important areas to work with our partners on.
I wish you good luck on this mission. What’s next in digital trials? How do you see this area evolving?
Observational studies were sort of the low-hanging fruit for digital clinical study designs. Given the tremendous breadth and depth of digital data that can be collected thanks to a growing number of digital health technologies and the growing acceptance of telemedicine, we are seeing a clear path to move from observation into the interventional space.
The most exciting aspect of this is that the advances we are seeing in research will also serve to transform the way healthcare is conducted, tapping into the true potential of remote patient monitoring.
I also see digital trials playing an obvious and vital role in the space of digital therapeutics. We’re already seeing policies being adopted to lay the groundwork in Europe, such as the Digital Healthcare Act 2019 (Digitale-Versorgung-Gesetz) passed in Germany or the National Institute for Health and Disability Insurance in Belgium paving the way for reimbursement of digital therapeutics. All of these efforts are in support of transforming healthcare, which I feel digital trials will contribute significantly over the coming years.
Can you please reveal what we can expect new from Scripps Research in the near future?
One of the things I’m personally excited about is that we’ve recently opened our research platforms to outside academic and industry collaborators.
We are now offering the use of our DETECT and PowerMom platforms to collaborators who want to run sub-studies on top of our baseline research platforms in the area of COVID-19/other respiratory illnesses and the area of maternal and postpartum health.
We’ve accepted five sub-studies this year and expect that number to grow quickly in 2023 as we add the capability in our sleep medicine platform, REFRESH, and our precision nutrition platform, PROGRESS.
Additionally, we are working with our technology partner, CareEvolution, to modularize the digital trial components we’ve developed for our trials and offer those modules to outside collaborators. These modules include e-consent, patient-mediated electronic health record capture/data visualization, patient education, wearable device capture, and personalized alerts and triggers.
We hope by offering these platforms and trial components to collaborators across the globe, we will further accelerate clinical research that reaches anyone, anywhere and advances biomedical research for all.
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