Jack L. Martin, MD
Senior Director, Cardiovascular Therapeutics
Senior Director of Product Innovation
The COVID-19 pandemic has led to the implementation of more efficient trial designs and operational execution, especially with regard to cardiovascular (CV) studies.
A greater number of alternative trial designs are emerging, given that this approach eases site and patient burden, and may facilitate responses to unforeseen risks to study execution. These include both fully decentralised studies which negates the requirement for the subjects to attend the traditional site, or more commonly a hybrid model, where site visits are reduced. Also, a rise in the use of digital health technologies — and in particular, wearable cardiac devices — along with home health and telehealth, may improve monitoring of clinical trial participants.
The increased use of cardiac devices was apparent even before the COVID-19 pandemic, with the wearable cardiac device market expected to grow to $6.2 billion by 2026, a CAGR of 22 percent, according to Global Market Insights1. One of the reasons for this growth is the impact of the coronavirus on CV patients, and an increasing number of initiatives to better understand and monitor this vulnerable patient population. Here, we review the digital health technologies impacting CV trials and the implications for future clinical research.
Using digital health technologies for remote monitoring to keep patients safe
More than ever, wearables are being used for remote monitoring, especially during the COVID-19 pandemic. Where appropriate and permitted, these devices can minimise physical patient contact by healthcare providers. The use of mobile electrocardiograms (ECGs), for instance, can generate important safety and efficacy data outside the study centre in real time, and aid the investigator in oversight without ever having to come into contact with the subject.
More importantly, there are a growing array of ECG connected devices that can capture digital endpoints that range from a simple rhythm strip to advanced analysis determined from a single, six- or 12-lead ECG. For example, the Nuubo ECG Vest, has been designed with the patients' comfort in mind and can be used to capture 2 channel ECG continuously for up to 30 days2.
Realising the full potential of remote patient monitoring to keep trial subjects safe during the pandemic, in June 2020, the FDA updated a guidance allowing manufacturers of certain FDA-cleared, non-invasive wearable devices to expand their use during the COVID-19 emergency3. This includes devices that measure common parameters of interest in CV trials such as blood pressure, pulse oximetry, activity levels and heart sounds via an electronic stethoscope.
In addition, there are a growing number of biosensors, such as patches from Vitalconnect and BioSticker™ from BioIntelliSense, which facilitates the collection of vital signs for 30 days. There are also interesting advances in the area of wrist-worn biosensors where devices are combining accelerometers with PPG sensors. These devices could be used to measure activity and sleep in addition to heart rate, respiration rate, SPO2, skin impedance (stress), temperature, blood pressure and other physiological endpoints. A number of companies have made great strides in this area including Apple, Philips, Withings, Samsung, Biobeat, Omron and Oura Ring.
Enhancing trial efficiency and patient engagement with digital health technologies
The use of wearable devices to capture and transmit patient data remotely and in (near) real-time not only can improve patient safety, but also can enhance clinical trial efficiency and patient engagement. For example, a phase 3, randomised clinical trial called CHIEF-HF (Canagliflozin: Impact on Health Status, Quality of Life and Functional Status in Heart Failure) is evaluating whether canagliflozin, a medicine for type 2 diabetes, can improve the quality of life in patients with heart failure4. This 2000-adult fully decentralised trial enrolled study participants with and without diabetes, and used a FitBit to measure changes in physical activity to support a secondary endpoint in a phase 3 trial. Even though the trial started at the beginning of the COVID-19 pandemic, it was able to launch and enroll patients when other trials were suspended or cancelled because the patient research was conducted remotely.
Moreover, new technology can be used to improve data quality in clinical trials by making data collection more complete or by filling in missing data. An example of this would be iRhythm Technologies’ Zio patch, which is being used by the University of California, San Francisco, to monitor heart rhythms in patients who have had COVID-19 infection5. Here, researchers are using deep machine learning to analyse the data with the hope that it can inform the short- and long-term effects of the virus on the heart.
Applying collected data, from clinical status to novel digital endpoints
In addition to improving clinical trial efficiency, the data collected from connected devices can be stored for future analysis or used in real-time where emergent intervention may be required. Connected device generated data can inform:
- Clinical status, such as when using QardioMD platform that allows the clinician to remotely monitor blood pressure, Sp02 levels (or blood oxygen saturation), heart rate, blood glucose and temperature at home. The data are analysed and used to generate a patient’s status, flagging those that are at high risk6.
- Medication adherence, an array of connected solutions can help support patients taking their medication with smartwatch or smartphone reminders7 that can be linked to smart pillboxes and smart bottles.
- Effects of certain patient actions on health outcomes, such as measuring the frequency of exercise and its impact on patients with CV diseases.
- Generation of novel digital endpoints that are more responsive to change than traditional assessment8.
Choosing digital health technologies for CV trials
As demonstrated, digital health technologies can help to minimise COVID-19-related disruptions to CV clinical trials and can expand the potential for real-world evidence to streamline data collection, potentially reducing trial costs and timelines. In fact, the era of COVID-19 has already accelerated the use of these technologies.
With the increased use of devices and sensors in clinical studies, there is a heightened awareness with respect to the selection of an appropriate device that supports the specific use case. Digital health technologies can reduce the need for clinical site attendance and enable data collection beyond the traditional clinical setting. When using a device to generate digital endpoints there needs to be sufficient scientific evidence to support that specific use case9 and the generation of an evidence dossier for regulatory submission. The same principles with respect to robust and reliable data also apply novel digital endpoints. Consideration is required for some of the unique operational issues, such as the logistics, device importation and site training. Once a valid data set has been determined, a robust documented process with respect to patient training, support and wear-time compliance monitoring is required. Data management and analysis, including strategies for handling source data, missing data and decisions on the integration of data into EDC, require specific knowledge and expertise.
At ICON, we have built a team with proven cardiovascular and digital health technologies expertise. Our team has gained operational expertise from conducting more than 50 digital health technology studies across multiple disease area and phases. In addition, our experts have built a framework based on best practices to support device selection and validation of novel digital endpoints.
Discover more by reading our white paper “Mitigating the impact of COVID-19 on cardiovascular trials.” Or contact us to speak with our experts about how we can help to keep your study on track.
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(1) Research Dive. Global Wearable Cardiac Devices Market to Witness a Tremendous Growth Due to COVID-19 Pandemic - Exclusive Report. August 2020. https://www.prnewswire.com/
(2) Nuubo. 2020. https://using.nuubo.com/en/
(3) Enforcement Policy for Non-Invasive Remote Monitoring Devices Used to Support Patient Monitoring During the Coronavirus Disease-2019 (COVID-19) Public Health Emergency (Revished). Guidance for Industry and Food and Drug Administration Staff. Food and Drug Administration. June 2020. https://www.fda.gov/media/136290/download
(4) A Study on Impact of Canagliflozin on Health Status, Quality of Life, and Functional Status in Heart Failure (CHIEF-HF). 2020. https://clinicaltrials.gov/
(5) Lim, Dion and Didion, Tim. UCSF studies how coronavirus attacks the human heart. ABC7 News. May 2020. https://abc7news.com/
(6) Qardio, Inc. 2020. https://www.getqardio.com/qardiomd-covid19/
(7) Dobkowski, Darlene. Smartwatch notifications improve medication adherence for AF. Healio and Cardiology Today. May 2020. https://www.healio.com/news/cardiology/
(9) Bill Byrom, et al. Selection of and Evidentiary Considerations for Wearable Devices and Their Measurements for Use in Regulatory Decision Making: Recommendations from the ePRO Consortium. Value in Health 11/2017; 21(6)., DOI:10.1016/j.jval.2017.09.012