By Ed Miseta, Chief Editor, Clinical Leader
Follow Me On Twitter @EdClinical
Patient recruitment and retention in clinical trials has long been an issue for pharma companies. Recruitment rates, even for oncology trials, remain mired in the low single digits. This results in many trials being delayed and even canceled.
One recent advancement that could help with both recruitment and retention is virtual trials. This concept, which allows patients to participate in trials without the disruption of having to make regular visits to a clinic, may be the key to better engaging patients by eliminating trial burdens. Although the concept has been around for years, it is still met with skepticism. In fact, many technologically advanced pharma companies have yet to venture into this arena.
Janssen is one company moving forward with virtual trials and taking studies to the patient. Darren Weston, VP, integrated data analytics and reporting, and Janssen Clinical Innovation (JCI) for Janssen, notes the company has a team focused on the investigator and patient insights and experience. After hearing feedback from more than 1,700 patients, one point was heard loud and clear: Patients wanted to participate in trials that were more integrated into their personal lives.
“We knew we had to conduct trials differently,” says Weston. “That feedback spawned the movement toward virtual trials. Although patients have been requesting this type of trial for some time, the emergence of medical-grade wearable devices and supporting technologies has made virtual trials even more feasible. As those technologies continue to advance, we should see more companies initiating these trials.”
DETERMINE THE RIGHT CANDIDATES
Janssen is currently conducting a virtual trial in immunology. Real-world evidence (RWE) was used to help enroll the patients, and multiple daily living assessments are being collected using an actigraphy watch. Janssen is currently working on operationalizing several additional trials with a direct-to-patient component.
To get started, a cross-functional team was formed that included leads from various therapeutic areas, as well as legal, quality, and other departments. Those individuals created a heat map to determine which studies and patient populations would most benefit from a virtual approach.
“Our discussions centered on determining the key factors that would make a virtual trial possible,” states Weston. “We looked at potential risks and the challenges we would face. By running all assets in our pipeline through the heat-map criteria, we were able to create a more distilled list of possible candidates. We then took a deeper look at those candidates to decide which ones we wanted to move forward into a virtual study. Not every trial is a good fit for a virtual approach, and knowing up front which ones are and aren’t is critically important.”
PREPARE FOR CHALLENGES
Weston believes, in the long term, virtual trials will be easier to operationalize than traditional trials. Still, he estimates the most significant challenges related to these types of trials will affect the sponsor companies, rather than patients, caregivers, sites, CROs, or other stakeholders.
“This is an entirely new way of conducting trials,” notes Weston. “Virtual trials will necessitate changes in SOPs and a change in mindset of your internal teams, including therapeutic areas, clinical operations, quality, and legal.”
Although virtual trials are intended to make studies easier for patients by not requiring them to travel to sites, other burdens may arise. Receiving accurate data from patients is of paramount importance, as is protecting the data and privacy of those patients. Since not all patients are tech savvy, some training may be required. This can be a concern when recruiting elderly patients or those who live in rural areas where there may be limited access to technology or the internet. Additionally, in the case of home nursing, some patients may feel their home is not tidy enough, or they have limited space for a home nurse to perform their duties. Thus, you need to recognize that even virtual trials can create unique burdens for patients.
To properly overcome these broad challenges in virtual trials, Janssen uses the aforementioned internal team, JCI, that has a ring-fenced (separate) staff an budget. One example of the type of challenge faced with this new way of working was determining when and how monitoring will be conducted within the virtual trial setting. The data monitoring plan had to be revised to support the immediate and ongoing review/monitoring of that data given that the data and source of data are entered directly into the digital platforms. Traditional approaches were largely manual, but with a digital platform in the virtual trial setting there is now an enhanced audit trail and traceability exchanged via emails, instant messages, and scans. For that reason, the process had to be adapted.
"Virtual trials will necessitate changes in SOPs and a change in mindset of your internal teams, including therapeutic areas, clinical operations, quality, and legal."
Darren Westen, VP, integrated data analytics and reporting, and Janssen clinical innovation, Janssen
One key component of success is collaboration. Weston stresses the importance of getting individuals from across the company to work together to make virtual trials a success. Solving problems that will inevitably arise requires individuals from different teams to cooperate. Having a myriad of teams operating in silos across the company will make the effort more difficult.
“This will be a new operating model for everyone in the company,” he says. “When you are in that early adoption stage, you need teams that are agile and willing to change. These individuals will work with technology companies, pilot the initial studies, and establish a successful process and model for everyone else in the company to follow. Some things will work, but some will not, and your team needs to be comfortable with that iterative cycle of development.”
HAVE THE RIGHT TOOLS
Of course, performing virtual trials requires technology solutions. Bringing in a technology company with an integrated platform is one way to fulfill that requirement. Wendi Lau, VP of operational improvement and reporting excellence at Astellas Pharmaceuticals, states there are several companies moving into this space and that many large CROs are now making significant investments in providing those technology capabilities, as well. At this time, she notes it may be too early to say whether companies should invest in their own platforms or simply go with a vendor providing an integrated approach. There can be arguments made in favor of either option.
“These technologies are advancing quite rapidly,” says Lau. “We are seeing significant growth and improvement in sensors and wearable devices. If a sponsor invests heavily in any technology, it must think carefully about the infrastructure to support it and the need to adapt to this rapidly changing environment.”
Furthermore, Lau cautions that a move to virtual trials is no simple endeavor. Wide support from within your organization is a necessity. She believes you need to have people on board who are of the right mindset, and you need to assess how virtual trials will impact your SOPs. Everyone will need to understand what the company really wants to get out of the effort. And of course, the right technologies and vendors will have to be selected and vetted. But, don’t underestimate the work that will need to be done.
“Some of the considerations will be very different from a conventional trial,” she said. “Planning needs to start early with the creation of the clinical development plan in order to ensure time to establish the processes and technology needed to support a trial conducted virtually. Ensuring endpoints can be captured outside of a clinic office in a validated manner is critical to establishing a path toward virtual trials. Another aspect that will need attention is the study protocol. That protocol must highlight the various aspects and needs of a virtual trial, which will be different from those of a conventional trial. This includes considerations for the communication plan and drug and supply chain management.”
DON’T FEEL THE NEED TO DO IT YOURSELF
Not all companies will have experts in-house who are familiar with the technologies required to conduct virtual trials. If a company is thinking about conducting a virtual trial, Lau’s advice is simple: Don’t try and do it alone.
“Engage with technology companies to guide you through this endeavor or hire a consultant with the needed expertise. Accessing someone who has done this before or worked through some of the challenges may help speed up the process. Many of the large CROs also will possess knowledge and capabilities. They have a good idea of the challenges that may arise and can help guide you through them.”
As far as challenges go, Lau believes patient safety is first and foremost. “As with any clinical trial, patients in a virtual trial need to be educated on how to communicate safety concerns,” Lau said. “There should be procedures that ensure the safety of patients is properly monitored and managed.”
If information is being collected from wearable devices, in addition to managing privacy and security, the integrity of the data collected is also a concern. If patients aren’t wearing the devices appropriately or if data is not being properly captured or transferred accurately, that can jeopardize the study. There must also be a way of attributing the data to the right patient. Regulators will want to ensure all these concerns are properly mitigated and managed.
"We are seeing significant growth and improvement in sensors and wearable devices. If a sponsor invests heavily in any technology, it must think carefully about the infrastructure to support it and the need to adapt to this rapidly changing environment."
Wendy Lau, VP of operational improvement and reporting excellence, Astellas Pharamceuticals
“This is where it is helpful to work with someone who has done this before,” states Lau. “I have read articles noting cases where patients were not wearing or charging the devices properly. When those things happen, the data becomes less reliable. Experts who have been through this before will know where the common risks reside and will know how to manage them so patient data is captured consistently and accurately.”
PATIENT-CENTRICITY SHOULD BE PRIMARY DRIVER
As far as the types of trials that would be a good fit for a virtual approach, Lau recommends looking at those areas where telemedicine is already being used as a starting point, such as dermatology and cardiology. Still, she points to a study conducted by the American Medical Association, published in 2018, which reported that only around 15 percent of physicians are using telemedicine in their practices. The technology is also not being used in many rural areas where virtual trials would be a good fit for patients.
For any company considering wading into the virtual trial waters, both Lau and Weston recommend remembering the real reason for implementing them. These trials can certainly lead to greater efficiency and cost savings, but the main reason for adopting a virtual approach should be to make the burden of trials easier on patients.
“This is a very patient-centric model,” says Lau. “By making participation in trials easier for patients, a virtual approach can increase patient enrollment and retention and enable trial access to more diverse patient populations. Technology advancements being made will continue to make these trials an increasingly more attractive proposition for all stakeholders.”