By Joseph Constance
As the COVID-19 pandemic continues to challenge the healthcare ecosystem, many organizations are turning to virtual, or decentralized, clinical trials to keep enrollees and staff safe while continuing their research and maintaining timelines and development goals.
In April and May, ERT, a global data and technology company specializing in clinical services and customizable medical devices, surveyed clinical professionals on how the demands of the pandemic were impacting their organizations’ use and planned use of virtual trial technologies. The report learned that:
- 82% of clinical trial professionals polled stated that their organizations are incorporating elements of virtual clinical trials because of the pandemic.
- Organizations will increasingly run full or hybrid virtual clinical trials in the future thanks to associated improvements in patient engagement, timeframes, cost effectiveness, and data fidelity.
- The biggest issue concerning 79% of participants is screening for new clinical trial patients.
- The most common ways to collect data in a virtual clinical trial are through telehealth (75%) and patient-used devices (75%).
- The primary issues impacting trials over the next six to 12 months are trial management (32%) and patient recruitment and enrollment (25%).
In addition, according to a report by Amwell, a telehealth platform, “Just as telehealth has transformed clinical care by increasing access, reducing burden, and lowering costs, telehealth is poised to do the same for clinical trials. The result will be faster, less burdensome, less costly, and more powerful trials that accelerate therapeutic development.” Establishing a telehealth program for a clinical trial entails access to necessary technology and services, establishing a core team, and defining use cases. The proper infrastructure will provide both patients and researchers with the necessary tools for undertaking an informed virtual trial, the report states.
An informal survey undertaken by TrialSite has found that some contract research organizations (CROs) and providers of clinical trial and research services, such as IQVIA, are experiencing growth in their virtual services as the pandemic forces people to self-isolate and stay at home.
In July, IQVIA Holdings and AstraZeneca began collaborating to speed clinical studies of the British drug maker’s potential COVID-19 vaccine in the US. The collaboration involves a large study of trial participants and will use IQVIA’s virtual trial solutions that would make elements of the study decentralized or remote.
IQVIA has established a suite of virtual research solutions. The company’s experience includes facilitating more than 70 decentralized clinical trials, including home nursing visits, and involvement in more than 200 remote patient engagement strategies incorporated into trials — patient recruitment and retention platforms, and e-visits-video dosing regimens.
And, virtual approaches to clinical research are utilizing digital technologies to relieve study sites of many, if not all, responsibilities of the research process — from identifying potential study subjects to screening them for eligibility to obtaining their consent for enrollment to entering their study data, according to CRO Syneos Health.
Bringing the Process to the Patients
The virtual concept makes clinical trials more appealing and convenient to the patient-enrollee because they bring the research process to patients, unlike requiring patients to bring themselves to the research process.
Janssen Pharmaceuticals and CRO PRA Health Sciences are partnering to launch the first heart failure drug approval trial using a completely decentralized, mobile design – a virtual clinical trial. The study is intended to optimize clinical research using a patient-friendly approach. It will use PRA’s mobile platform and wearable devices to more efficiently gather real-world evidence directly from patients.
The clinical trial — called CHIEF (Canagliflozin: Impact on Health Status, Quality of Life, and Functional Status in Heart Failure) https://clinicaltrials.gov/ct2/show/NCT04252287 will assess the effectiveness and safety of Janssen’s canagliflozin (Invokana) in adults with heart failure. This is reportedly the first fully virtual trial to support approval of a new drug indication. Patients can participate from home using their phones and computers.
Expandable Virtual Elements
And we see that a spinoff of the Mt. Sinai Hospital in New York is launching a virtual trial network in collaboration with the American Gastroenterological Association. Rx.Health, the spinoff, has developed a TrialEngage toolkit to help researchers improve patient engagement in virtual and decentralized clinical trials. Patients will be walked through the registration and informed consent process. They will receive wearables or other remote monitoring devices, lab results, and virtual appointment reminders. They also will be able to access telehealth. The toolkit connects into electronic medical record (EMR) systems.
The intention was to develop expandable virtual trial elements that could be used to start trials virtually. By offering trial participants the option of reporting for a few in-person appointments instead of several, more patients from a wider variety of regions would participate, they assumed.
Mt. Sinai has experimented with virtual clinical trials in the past. Researchers with the Icahn School of Medicine at Mount Sinai and colleagues elsewhere reported in the JCO Clinical Cancer Informatics in 2017 the results of a telemedicine clinical trial of involving prostate cancer patients. The investigators wrote, “Telemedicine-enabled prospective cancer clinical trials are feasible and may overcome geographic barriers to trial participation. As the platform is refined, technology improves, acceptance increases, and regulatory barriers are addressed, use of this platform may be extended to other malignancies, interventions, and disease states.”
Some Caution Needed
As we have said previously, going virtual isn’t as easy as just flipping a switch. Implementing virtual trials comes with a number of challenges. The industry has been hesitant because of concerns around patient care, how to collect needed data in a reliable way, and regulatory requirements.
Risks involving the security of data collected during virtual trials are an issue. The challenge involves establishing security for a clinical trial that may entail hundreds of data input points, networks and applications, and patient devices. Wearables, smart phone apps, telemedicine platforms, and remote testing kits may cause data issues. It is key to review platform capabilities, checking for usability; HIPAA compliance; an open network; and the ability to enable participants to use their own devices.
In addition, there are many practical and regulatory challenges to conducting virtual trials. For example, undertaking a virtual trial across state lines raises state licensure issues because investigators cannot deliver medicines or prescribe treatment to study participants located in a state in which the investigator is not licensed.
But Moving Ahead
Still, the transition to virtual trials is moving ahead, as trial sponsors and their CRO partners believe in moving forward with candidate therapies during the pandemic. The Australian National Health and Medical Research Council has released COVID-19 guidance that indicates that employing digital strategies to continue clinical trials during COVID-19 is acceptable, and now encouraged, after required approvals are obtained.
ICON plc, an Ireland-based CRO, is offering guidance on how to implement virtual clinical trials for late-phase research directly with patients. As the company indicates, some post-marketing evidence requirements can be met with virtual studies. Even when it is not possible to eliminate traditional sites, their burden can be reduced by using the proper approach to the protocol and some creativity.
Drug makers should be open using a virtual approach for research. It might be the case that making a few minor alterations to a protocol can make it possible to undertake a study virtually instead of using traditional sites.
Medpace, a CRO, has established a COVID-19 site management and monitoring plan, which includes the use of virtual monitoring visits; easy to use tools, such as FaceTime, for site personnel; and remote access to electronic medical records EMRs.
Medpace has implemented and trained clinical research associates on the conduct of virtual monitoring visits, including site initiation visits and site study-specific training. The company’s services include: virtual or home visits with patients, including direct to patient shipments of necessary study supplies; the creation of teaching videos for patients; IP delivery; IP administration; diary inputs; and the like. There also are updated protocol and clinical study report templates for COVID-19 adaptations.
On the Academic Front
Meanwhile, Mark Pletcher, MD, MPH, a general internal medicine physician and professor of epidemiology and biostatistics at the University of California at San Francisco, is running a US-based virtual clinical trial. The PCORnet Blood Pressure Home Monitoring study is a patient- level randomized controlled trial that will compare the effectiveness of home blood pressure monitoring using a linked smartphone application to help patients with uncontrolled hypertension achieve a reduction in systolic blood pressure (SBP).
The trial, which has an estimated completion date of July 30, 2021 and is still recruiting, is being conducted within the National Patient-Centered Clinical Research Network (PCORnet), which supports a research network that enables distributed querying of electronic health record (EHR) data in a common data model. The trial also is using the Eureka Research Platform, an online research platform hosted by the university that supports eConsent, online surveys, and data collection from devices, such as high blood pressure monitoring devices.
Data from these two sources will be used together to accomplish the study aims. Participation in the project poses minimal risk to participants because high blood pressure monitoring is the guideline-recommended standard of care (without specification of smartphone linkage). The monitoring devices and the app are all commercially available and currently in use. Clinicians, with input from patients, will maintain full control of how blood pressure is clinically managed.
Investigators designed a patient-level randomized controlled trial that compares the effectiveness of smartphone-linked versus standard high blood pressure monitoring to help patients with uncontrolled hypertension achieve a reduction in their SBP, and patient satisfaction with the device. They intend to enroll 2,000 patients randomized in a 1-to-1 ratio to receive a smartphone-linked or standard monitoring device. Participants will use blood pressure medication prescribed by their physicians.
The researchers are using data from the EHR, an online patient portal, and the home blood pressure monitor, in the smartphone-linked arm, to collect outcome data for a period of at least six months (for the primary outcome), and up to 18 months (for secondary outcomes, depending on the enrollment date). The primary blood pressure control outcome will be reduction in SBP, by clinic measurements, at six months. The primary patient satisfaction outcome will be the net promoter score derived from the self-reported likelihood of recommending the device to a friend, at six months.
Pletcher explained that participants must have received a diagnosis of high blood pressure and must consent to use of their EHR data. Essentially, participants will receive monitoring devices containing software that they can download to their smartphones.
To make the virtual clinical trial work, two clinical research coordinators support patients participating in the study by working with them over the phone, answering questions, and helping with technology issues. They are not involved in recruitment. “We’re running the study with a very small staff,” said Pletcher.
The blood pressure trial is a pragmatic trial, intended to evaluate the effectiveness of interventions in real-life routine practice conditions, according to Pletcher. “Pragmatic trials are a move toward simpler trials with fewer exclusion and inclusion criteria, incorporating simple and realistic intervention protocols, and targeting real-world outcomes. The intervention is not tightly controlled.
“Our intervention uses software apps and devices,” he added. “We have fewer issues than other remote trials since no medications are involved, nor prescriptions required. Issuing the monitoring devices is not a problem, and patients are using their own smartphones. However, individual states have different regulations for accessing EHR data, and these regulations must be complied with,” he stated.
Among advantages, Pletcher indicated that recruiting for a virtual trial is less expensive than recruiting for a traditional clinical trial. Participant invitation to a virtual trial can be sent electronically with ease, unlike in a traditional trial in which volunteers have to report to a physical site and be interviewed by staff, which can be inconvenient for some. Emails can be followed up with phone calls, but this starts raising costs, he noted. “On the other hand, when you meet and interview people face to face, it’s easier for staff to make a connection and establish a relationship with someone, and this is helpful for patient engagement,” Pletcher said.
For sure, virtual clinical trials are here to stay. What started as a battle response in the war against COVID-19 is becoming permanent, like so many changes caused by the pandemic.