A behind-the-scenes look at the mSToPs clinical trial with Dr. Steinhubl.

According to three-year results of the mHealth Screening To Prevent Strokes (mSToPS) clinical research study,¹ which were recently published in PLOS One,² electrocardiogram (ECG) monitoring of asymptomatic individuals can lead to earlier diagnosis of atrial fibrillation and can potentially contribute to preventing adverse cardiac events, furthering the case for cardiac screening.^3,4

JUMP TO A TOPIC:

• How was the approach different than typical clinical trials?
• Did the study reveal what to consider after an atrial fibrillation (AF, AFib) diagnosis?
• Did the study make you think differently about the way healthcare operates?
• What are you seeing as next in screening for AF?

Led by researchers at the Scripps Research Translational Institute (SRTI), the three-year outcomes were presented at the American Heart Association⁵ in November 2020. The innovative, direct-to-participant study design relied on self-applied Zio XT patches (a digital healthcare solution) to effectively monitor a large population of participants from Aetna fully insured Commercial and Medicare health plans.⁶ Eligible Aetna members were identified across the United States based on risk factors for AF.⁷ The mean wear time for each ECG monitor was 11.7 days, with 97.8% analyzable data.⁸ The study looked at occurrences of AF diagnoses and the clinical events surrounding each diagnosis for members of the monitored cohort and the control cohort that underwent routine care.⁹

The study found that participants diagnosed with AF through screening had lower rates of stroke, systemic emboli, or myocardial infarction than those in the control cohort who were diagnosed with AF through standard clinical care.^10,11

We spoke with Dr. Steven R. Steinhubl, the former director of Digital Medicine at Scripps Research Translational Institute and principal investigator of mSToPS to get his firsthand perspective about the study.

(This interview has been edited for clarity and length.)

Please tell us about your idea for the mSToPS study. How was the approach different than typical clinical trials?

Dr. Steinhubl: One large area of unmet need in healthcare is stroke prevention. Clinicians, patients, and payers were all interested in preventing strokes and wondered if using novel digital technologies might be used to address this huge problem. We felt that screening for silent AF would be one of the best, most actionable ways to take advantage of what digital technology could do. This had not really been studied before, so that's how we started, to address that problem.

Dr. Eric Topol¹² who heads Scripps Research [Gary & Mary West Endowed Chair of Innovative Medicine, Scripps Research; Executive VP, Scripps Research; Professor, Molecular Medicine, Scripps Research; Director & Founder, Scripps Research Translational Institute Department of Molecular Medicine, California Campus] and I had been in clinical research for a long time and thought the multicenter model, in which patients have to live close to an academic medical center and then come to that medical center for all trial interactions, was a model that prevented a lot of people from participating in research.

We were committed to designing a trial that was more participant-centric, where every aspect was built around them as much as possible . . . this was in our heart and was our motivation in designing the trial. The high-quality ECG patch [Zio XT] really met our needs. It allowed us to design a trial around the technology’s capabilities and eventually led to the mSToPS trial. Aetna’s Healthagen Outcomes unit was also instrumental in making the trial possible because it identified the need to conduct an AF screening study.

We were fortunate to partner with Janssen Pharmaceuticals for financial support, but beyond monetary support they were also wonderfully visionary and innovative collaborators throughout the entire mSToPS process.

From the beginning we were committed to designing a trial around the participant while remaining scientifically valid. This led to the trial being one of the very first ever to be built in a direct-to-participant format, now frequently referred to as siteless or decentralized clinical trials.

Another critical part of our commitment to being participant-centric was to return all information to the participants. It is odd to recognize that is not the norm in clinical research. Typically, when you sign up for a research trial, you never get your results during the study or hear anything back once it’s over. With mSToPS, we made sure that participants knew we would give them results back. That ended up being one of the more interesting learnings — how interested people were in the results, not just their individual findings, but the actual full results. . . . In addition, we didn’t want to just dump meaningless data on our participants. It was important to provide their results in context and answer any of their questions about the results, but while avoiding providing any direct medical advice.

Did the study reveal any nuances about what to consider after an AFib diagnosis?

Dr. Steinhubl: For so long, identifying AFib has been all about whether we start people on anticoagulants or not, and that’s certainly a hugely important question, with stroke prevention as the major motivator. It’s what motivated mSToPS. But I’d argue that finding AFib should lead you down the path to do more than just deciding on whether to anticoagulate a patient or not.

Rather, it should lead to questions like: Do I more aggressively look for sleep apnea? Do I have a long conversation about alcohol abstinence? Do I double-down more on the importance of weight loss? As well as preventions, making sure there’s adequate rate control so you don’t risk tachycardia-induced cardiomyopathy, all on top of thinking about anticoagulation and the risk/benefit of that.

Did the study make you think differently about the way healthcare operates or the effectiveness of telehealth?

Dr. Steinhubl: I would say the origin of the Digital Medicine Division at Scripps Research Translational Institute was around the concept that healthcare is broken and desperately needs to be fixed on multiple levels — cost, convenience, disparities in care, etc. It’s built on the way medicine was forged over centuries, where you come see the healer when you have a problem but not until you have a problem. The approach is sometimes described as a sickness care system, not a healthcare system. We think that digital technology can have a big impact on that.

We made assumptions with mSToPS and learned many lessons. The biggest lesson, and in retrospect should have been obvious, was the erroneous assumption that once a participant enrolled, that once we sent them their Zio patch, that they would automatically just put it on and follow the study protocol. While the majority did do just that, approximately one-third did not. Part of that was likely due to the fact that as part of the randomized study, half the study group was delayed by four months before they got the patch. In addition, the average age of people in our study was 73, so some were snowbirds and lived in different locations at different parts of the year, and others might have had life changing events during the four month gap between enrollment and planned monitoring. Maybe, they simply changed their minds. A lot happened from the time they consented to the trial and the time they received the patch.

At the time we designed the trial, I didn't appreciate the importance of ongoing communications. We self-selected in the study through people who responded to email because the vast majority of recruitment was through email, so we could have easily sent an email a week before or the day we thought they were going to get the device. A quick ‘hey how's it going, this is coming,’ note would have helped keep participants engaged in the study, which is critical with any screening program.

People have an inherent trust in their healthcare system and their doctors. But when you do something remotely, that inherent trust is missing — which I think is okay. This just means you have to earn the trust and, to do so, you have to be transparent, communicative, and available. There’s no one-size-fits-all communication, each patient will have unique communication needs, and, in the future, we should be able to meet those specific needs for each individual’s level of comfort.

We learned a lot, and that’s actually informed large studies we've done in the COVID population and other projects. We're going to get better and smarter in the long run and that will translate into patients receiving more healthcare and less sickness care.

What are you seeing as next in the area of screening for AF and health screening in general?

Dr. Steinhubl: I think there's no area in medicine, except for COVID, where more ongoing research is happening than in screening for AF. This will end up helping people in the long run, keeping them safer and healthier. We're learning a lot.

In addition to screening based on age and comorbidities, there's been some really interesting work on genetic risk scores as well as really innovative research around using machine learning to look at 12-lead ECGs to predict future AF. Other work has used artificial intelligence to predict future AF based on EHR data. All three of these areas of focus are likely complimentary and together will help improve screening and may eventually prevent irreversible complications of AF.

What's also exciting is just how much digital technologies are changing all of clinical research. And the rapidly changing availability of ever improving sensor technologies that are available to track a person’s health in multiple different ways are going to all translate into good things for patients. I'm very biased, as this is my area of research, but I think it's super exciting what the future holds for the technologies that can identify and learn about an individual’s normal physiology.

(End of interview)

Read the study.

Overall, the results of the mSToPS study suggest there is an unmet need to screen for AF. Read the mSToPS study and the recently published three-year clinical outcomes.

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Steven R. Steinhubl, MD

Senior author of the mSToPS clinical trial and a career-long clinician-scientist and the founding director of Digital Medicine at Scripps Research’s Translational Institute. In 2021, Dr. Steinhubl began dividing his time between Scripps and physIQ where he is chief medical officer. He also remains clinically active as a cardiologist for the Alaska Native Tribal Health Consortium. He has over 20 years of experience in clinical research and has served as the principal investigator on numerous national and international trials. Dr. Steinhubl has published more than 280 peer-reviewed manuscripts.