Are We Ready for Decentralized Clinical Trials?

Source: BioSpace

Decentralized clinical trials gained a foothold in the pharmaceutical industry amidst the COVID-19 pandemic and will continue to be used once the pandemic ends, according to panelists at BIO 2020, speaking Thursday in a virtual session.

The chief benefit of decentralized clinical trials is the options it brings to patients. “There is a lot of opportunity for more of us to participate in trials that are decentralized,” said Valerie Paradiz, VP, services and supports at Autism Speaks, and an autism patient herself.

Autistic patients, as well as those with other conditions, experience a range of characteristics that affect patients’ lives. They include varying degrees of communication issues, responses to sensory input and focused interests that can impede relationships or fulfill lives, Paradiz explained.

In a clinical setting, distributed trials could open the door to people who can’t leave home easily or as frequently as needed for them to participate in traditional clinical trials. “Distributed trials, therefore, could capture new kinds of data” by including those populations. “The keyword is ‘options,’” she said.

The “all hands on deck” approach to the pandemic by Congress and the FDA set the stage for clinical trial innovation. “It has set up a lot of conversations about where telehealth is, and where it will be six months from now,” Wade Ackerman, partner at Covington & Burling, said. “When the new Congress convenes in January, it will have an 18-month runway to the next FDA user fee authorization, so there will be significant policy discussion on the Hill about these issues.”

Not surprisingly, defining the terms around decentralized trials is foundational. “People often use the terms decentralized, remote, virtual and hybrid interchangeably,” moderator Rasika Kalamegham, group director, US regulatory policy at Genentech, noted.

In actuality, their meanings are quite different. Isaac Rodriguez-Chavez, officer for clinical research methodology, regulatory compliance & policy development within FDA’s, Center for Drug Evaluation and Research, explained. “At the Agency, ‘decentralized trials’ refers to the decentralization of technologies. These clinical trials use digital technologies to have remote interactions with real participants. In contrast, virtual trials are preclinical trials conducted in silico or on models. Both examples use digital technology, but their application is different.

“Hybrid trials combine elements of traditional and centralized approaches,” Rodriguez-Chavez continued. Here, some patient consultations or tests may be performed remotely and others in person at a trial site. Which trial design may be best used depends on the trial’s goals, the patient population and the available technology.

The technology itself is a major consideration. “For a simple example, having to go to a trial site for a blood draw rather than having the option to have blood drawn at home could be a deal-breaker for some individuals,” Paradiz said. In autism, reducing a person’s anxiety by their not having to process the additional information of a clinical setting, reducing wait times (and, thus unstructured time) and communicating in multiple ways are simple elements that have great impacts on trial participants.

What can be measured during trials depends on the wearables selected for the study. “Wearing a device for the duration of a trial can be intrusive. Even playing a game or using an app on a regular basis takes a lot of effort, so it’s challenging to identify the right technology to use. When integrating technology into a study, you want to consider the comfort level of the patient,” Kalamegham said.

Paradiz recommended getting input not just from the intended trial participants, but also from industrial or cognitive engineers to optimize the experience and ensure the right data is obtained at the right quality.

Patient education should play a role, too, panelists advised. “It’s important to educate study participants about the study’s purpose, how to use the technology and how to get used to it.” To do this, Paradiz recommended consulting real-world evidence showing how your particular population consumes and retains information. That could mean developing a social narrative or step-by-step videos, like task analyses, she added.

As decentralized trials become more necessary, pharma sponsors are looking for guidance. “There’s an inertia in the FDA and in the industry,” Ackerman acknowledged. “There’s already a tried and true pathway for clinical trials, so does any sponsor want to take risks (by using decentralized trials)?”

Normalization will be more likely after the FDA issues its decentralized guidance, tentatively scheduled for later this year. “It represents an expansion of clinical research from traditional to decentralized trials,” Rodriguez-Chavez said. It will include hybrid trials, as well. “The whole Agency is engaged in this topic.

“The technology must make sense for the context in which it is used,” he continued. “For us, it comes down to following 21CFR Part 11 guidelines.” He defined that as having an audit trail for the technology and for everything that occurs, as well as robust and reliable data.

For instance, the sensors and wearable devices used in the trial must be customized, verified and validated – in addition to the verification and validation studies conducted by their manufacturer. “This is to ensure you are measuring what you intend to measure,” Rodriguez-Chavez explained.

“Because of a public health crisis, the industry has pushed to adopt technology that otherwise would have been adopted in a step-wise approach,” Ackerman noted. “The promise is there, but there are cautions, too. There are a lot of layers to work through, and a lot of thought must be given to each step.

“I encourage people to collaborate with the FDA in evolving areas,” Ackerman concluded. “Keep a positive mindset and be engaged as you hit the gray areas.”