At the start of the COVID-19 pandemic, ICON initiated the CHIEF study, a fully decentralised cardiovascular trial, intending to demonstrate that a drug reduced symptom burden in patients with heart failure at twelve weeks. While COVID-19 presented many challenges, ultimately the decentralised model proved to have clear benefits for patient diversity, retention and compliance. These benefits have since been corroborated by fully decentralised and hybrid trials within the cardiovascular space and other therapeutic areas.
Now, the necessity of rapidly decentralising clinical studies during COVID-19 has been replaced with the intentional development of fully decentralised and hybrid clinical trials, which include elements from both traditional site-based and decentralised clinical trials. Their staying power, post-pandemic, has been further reinforced by the United States’ recent enactment of the Food and Drug Omnibus Reform Act of 2022, which includes provisions intended to improve diversity in trial enrollment through decentralised clinical trials and associated digital health technologies.
We reflect on the success of the first fully decentralised cardiovascular trial implemented at the beginning of the COVID-19 pandemic, and highlight some of the key elements that need to be in place in a decentralised or hybrid setting to realise similar benefits in future trials.
At-home options increase diversity in patient recruitment
Decentralised and hybrid clinical trials overcome two common hurdles for patient recruitment and retention: accessibility and convenience. In our most recent survey in 2021, 90 percent of respondents were not willing to travel more than one hour to participate in a clinical trial. As a result of the physical distance, the burden of travel, and related financial and time investments, site-based trials exclude significant populations. This becomes an especially important factor in long-term cardiovascular trials. Providing decentralised options that improve accessibility and minimise burdens can translate into increased participation from diverse communities.
Besides eliminating travel burdens, the recruitment methods used in decentralised trials can also result in more representative trial populations. Recruiting at the institutional level may eliminate some of the recruitment bias at the investigator level seen in site-based trials. In addition, at-home options can open recruitment eligibility to more rural communities. Together, reduced patient burden and an increased range of eligible patients can result in more representative trial populations.
For the CHIEF study mentioned above, investigators noted greater diversity compared to traditional chronic heart failure trials, which, historically, have under-represented women and lacked racial diversity. Of the patients enrolled, 52 percent were women, and 15 percent were African American, which is reflective of the general US population and higher than prior heart failure trials. In addition, the study enrolled a wide age range of 22 to 91 years, with a median of 64 years.
Other decentralised trials have observed improved inclusivity as well; one North-America based study quickly recruited a representative population (51.6 percent) of female participants from a broader geographical range than is typically seen in site-based trials. In another fully decentralised U.S. study, 25 percent of enrolled participants were black, far more than the standard U.S. recruitment rate of around 4 percent.1
Reducing patient burden with mHealth and wearables
When mobile health (mHealth) and wearable technologies fit seamlessly into patients’ lives, they can support decentralised trial designs and lower trial costs. For instance, many cardiovascular trials require that patients visit sites so that their heart rhythm and or/vital signs can be rechecked – steps that could be unnecessary with wearable technologies that can take biometric data from patients as they go about their daily lives, reducing or eliminating the need for frequent study visits and associated travel.
Digital technologies are proving to be especially useful in cardiovascular trials, because they can capture physiological and real-world data that dovetail perfectly with the signals sought in cardiovascular trials – perhaps more so than in any other therapeutic area. In fact, the digital biosensors available today capture many of the significant endpoints sought in cardiovascular trials. Common mHealth devices include wearable blood pressure monitors, and patches that can produce electrocardiograms – which measure the electrical activity of the heart, and can be used to detect irregular heartbeats. In the CHIEF study, a Fitbit was used to measure accelerometry, a measure of activity that served as the key secondary endpoint. The primary endpoint was based on electronic patient reported outcomes (ePROs) from the Kansas City Cardiomyopathy Questionnaire (KCCQ), which measures patient’s perceived heart failure symptoms and quality of life.
While many companies sponsoring cardiovascular drug trials are interested in using more than one device in a study to measure multiple parameters, that temptation must be balanced with the need to “keep it simple” from the patient’s perspective. Multiple technologies, or a digital technology that is not easy for patients to use can increase patient burdens or reduce compliance, especially in decentralised settings. To support patient centricity, the digital devices must have “maximum passiveness” so that data collection is seamless and unobtrusive. The interface must be simple and convenient to use, and for wearables, the device should also be attractive to wear.
Improving compliance with concierge services
While replacing some, or all, study visits with in-home services can reduce patient burdens related to travel, it can also introduce situations in which patients feel disconnected, ill-prepared or confused. Dedicated concierge services that act as a direct-to-patient contact team are important to ensure patient support is fully embedded in decentralised or hybrid trials.
The expertise to fully support patients in setting up connectivity to digital platforms, devices and wearables should be considered where digital health technologies are included in the clinical trial. And while assisting patients with technical support is essential, ensuring retention requires engagement beyond technical support. Direct inbound and outbound communication with patients improves overall engagement, compliance and retention throughout the trial by onboarding the patient and being a central contact for any challenges they might come up against.
Combining concierge services with remote monitoring and patient engagement apps helps detect compliance issues and allows reminders or other interventions to keep patients on protocol. By increasing touchpoints with trial participants, sponsors can make sure patients are filling out their eDiaries or generating ePROs, for example, on a scheduled basis. They also help to track data from wearables such as electrocardiograms and blood pressure monitors, and can help to resolve any technical problems or human error if data is missing.
In the case of the CHIEF study, concierge services proved to be an effective strategy to engage patients remotely. Following trial enrollment, 98 percent of patients confirmed eligibility, and 0 percent of participants took prohibited medication post-enrollment. Patient compliance was also very high with more than 97 percent ePRO compliant, 95 percent eDiary compliant and 80 percent medication compliant.
Looking to the future of decentralised cardiovascular trials
ICON’s successful delivery of the first fully decentralised cardiovascular study at the beginning of the pandemic has since been replicated many times over, demonstrating that a decentralised or hybrid trial design can improve how clinical studies are conducted, and enhance compliance and diversity. However, a decentralised model does not guarantee benefits to patients. To be successful, in-home services and digital health technologies need to be integrated into the trial design in a way that delivers a seamless trial experience for the patient. With accessible technology, and consistent direct-to-patient contact, cardiovascular patients can receive necessary support, while sponsors gain the benefits of increased patient diversity, retention and compliance.
Explore the successful strategies that ICON deployed in a fully decentralised heart failure study or contact us to speak with our experts about how we can support your cardiovascular clinical trials.
Citations:
Goodson N, Wicks P, Morgan J, Hashem L, Callinan S, Reites J. Opportunities and counterintuitive challenges for decentralized clinical trials to broaden participant inclusion. npj Digit Med. 2022;5(1):1-6.