Two Sponsors And A Site Expert Walk Into A DCT Discussion

By Life Science Connect Editorial Staff

Love or hate them, decentralized clinical trials (DCTs) have been a polarizing concept in the pharmaceutical industry since the early days of the COVID-19 pandemic. Despite the hype, questions remain about whether DCTs are the future of clinical trials. Meanwhile, DCTs involve several new and emerging technologies, adding to the complexity of managing a clinical trial. Debates abound regarding their cost-effectiveness and patient centricity, while regulatory authorities work to ensure that they meet the same criteria as on-site trials.

When you strip away the hype and talk to experts in the industry about their experiences with DCTs, the reality is not as clear-cut as the debates surrounding them. Clinical Leader Live delved into the experiences of running DCTs by turning to two sponsors and a site owner in DCT's Opinions, Experiences, And Regulations.

Phil Ambery, MD, global clinical head at AstraZeneca in Sweden, and Oscar Segurado, MD, chief medical officer of gene therapy company ASC Therapeutics, were joined by Daniel Fox, Ph.D., founder and CEO of the Clinical Research Payment Network, for a lively discussion on the realities of DCT deployment, how the FDA and other regulatory authorities are responding to DCTs, technology adoption, and whether DCTs have the potential to make life easier or harder for patients and sites.

Do DCTs Help Or Hinder Clinical Trials?

Ambery shared that his first experience with DCTs was a diabetes study that relied on remote glucose monitoring, but more technologies have emerged in recent years to collect data directly from participants. For example, blood pressure monitors can be used at home for certain trials, and the data can automatically be uploaded to a cloud-based platform. He described a kidney trial that used remote weighing scales that checked for fluid retention daily and a blood pressure monitoring device. These devices uploaded information to an iPad that sounded an alarm when patients hadn’t taken their medication or weighed themselves properly. However, the trial did not proceed as smoothly as anticipated.

“Tech companies sometimes test devices on their young employees, but that doesn’t always translate to elderly people who may struggle to use them,” Ambery elaborated. “Some of our patients couldn’t use the iPad correctly or had difficulties with their home Wi-Fi. Soon, so many iPads were sending alerts to the sites that they would spend an entire afternoon answering alarms from their patients.”

Segurado shared his experiences with DCTs from a startup company point of view. ASC Therapeutics used home-based HCPs as a patient-centric way to incorporate DCT methodologies into a study investigating gene therapy for second-generation hemophilia A. Segurado explained that, as is common with gene therapy, administering the drug only happens once, on-site, with the PI's supervision. However, the trial also required complex follow-up visits. With this drug, investigators needed to consider the efficacy parameters, which, in the case of hemophilia A, means looking into Factor VIII activity, which is the coagulation factor missing in these patients. Also, an HCP needs to take several vital signs from the patients and perform other lab work, which they could perform in patients’ homes.

“The challenge with this study is that the condition is rare, and we had to adapt to fit patients’ needs, including using DCT methods,” Segurado explained. “For example, one patient lived 150 miles from our PI site, so we engaged local HCPs and activated a plan we'd already established for the entire trial to use a CRO's mobile clinical services. As a small company, we work with CROs, CMOs, and CDMOs for manufacturing and other services, including a company that ensures that the kits needed for patients are either at the central site or can be sent to patients’ homes.”

Fox shared that the pandemic-inspired rush to make DCTs feasible resulted in a chaotic environment for sites where competing vendors offered solutions that increased sites' burdens by requiring them to learn new technologies, provide DCT oversight, and manage complex logistics. He explained that DCTs required as much work per patient as an on-site trial during those growing pains. However, sites are willing to accept them because they recognize that DCTs can improve enrollment.

“From the site’s perspective, DCTs boil down to community outreach,” offered Fox. “It’s a matter of reaching out to the community to engage people in clinical research, and many sites are being very creative with DCTs and using them to boost engagement, even though they can be as much work as a traditional trial, and sites don’t directly benefit from them.”

How Have Regulatory Authorities Responded To DCTs?

Fox opined that DCTs would have become popular before the COVID-19 pandemic, except that strict FDA regulations discouraged them. However, when the pandemic forced trials to pivot to DCTs rapidly, the FDA eased its requirements to allow them to advance. The agency also has upcoming draft guidance that requires protocols to define visits that would be DCT compliant, indicating a shift toward more acceptance of DCTs. Despite these encouraging signs, the panelists agreed that regulatory authorities are concerned about how DCTs can meet patient privacy standards, provide adequate patient care through fully qualified off-site HCPs, and safeguard data security.

Ambery stated that IRBs are particularly concerned about protecting patient privacy and ensuring that all electronic communications are safe and secure from hacking, which makes it challenging when sponsors use leading-edge technology in their trials. For example, his company wanted to use an app for a study in France that recorded DCT information and uploaded the data to an EU cloud-based platform. The IRB refused to greenlight the app over privacy and cybersecurity concerns. Likewise, geofencing could be a valuable tool to track participants’ clinic visits, but it also raises significant privacy concerns.

Ambery explained that just because a device is approved for medical use doesn’t mean that the FDA will allow it to be used in a clinical trial. For instance, participants may wish to use a specific wearable technology for a trial, such as a popular smartwatch, but those devices may not be compliant. Ambery expects the FDA to become more amenable to cutting-edge and commercially available remote technology as DCTs continue to grow in popularity. Segurado added that the FDA recommends engaging central IRBs to monitor patient privacy and compliance with digital health technologies when initiating a DCT. “Whether we’re discussing traditional centralized clinical trials or DCTs, the FDA wants us to ensure data integrity, quality, and safety,” he clarified.

Why Is DCT Adoption Low?

1. The pharmaceutical industry is notoriously risk-averse when adopting new methodologies, including DCT technology. In fact, according to a 2022 ACRP report,¹ DCT technology utilization lags behind other trial technologies, and less than one-half of sites report currently running trials that use DCT components or services. Also, sites rarely use remote technologies that could support patient convenience. According to Fox, this is not surprising given that even now, only about 28% of sites use any electronic format for their clinical trial operations.

Segurado explained that one issue is that many trials happening today started several years ago before the FDA allowed electronic data collection or DCT technology. Given that the industry moves slowly and carefully into new methodologies, he predicts it will take some time before pharmaceutical companies widely adopt DCT technologies.

Ambery likened new technology to a new relationship. Initially, there's a lot of enthusiasm and focus on the relationship. But as time passes, you step back and realize that you don't need to spend as much time with your new partner as you did initially. Likewise, the pandemic engendered industry-wide excitement over the possibilities of DCTs. However, with experience, sponsors have learned that DCTs bring unique complications. Fox agreed that DCTs have great potential, but companies rushed to deploy them too quickly without realizing the ramifications for sites. Segurado stated that companies and sites must find a balance that prioritizes patient care.

How Do Site Perceptions Influence DCT Acceptance?

Fox’s stories about overwhelming and overburdening sites with DCT technology are not unusual. Ambery shared that AstraZeneca has pioneered the Unify platform, which provides a single login for sites to reduce the time spent managing multiple logins and passwords. Fox added that sponsors should remember that sites often run several studies in tandem, each with unique needs.

“To understand the site perspective, imagine you’re running a restaurant and every customer said, ‘You must cook my food with this spatula and only this spatula,’ so you had a kitchen filled with a hundred spatulas to manage,” Fox elaborated. “The AstraZeneca platform is great, but we also work with other sponsors who are asking us to use other technologies. Eventually, I think we'll get to a point where we have a universal understanding of what can be done in a trial and what can be built into a protocol. Still, sites should have a say in what technology they use to complete the trial."

Segurado also emphasized that sponsors live in a "technology library tower," where they spend their days using laptops and smartphones, but that's not necessarily the case for patients. Many patients lack access to the technologies that pharmaceutical companies take for granted. Thus, more technology does not necessarily equal better patient care.

Are DCTs Patient-Centric?

"I use the term 'decentralized centricity' to demonstrate that while we decentralize the clinical trial, we remain patient-centric,” stated Segurado. “We must ensure that the patient is at the centerpiece of every trial. On that basis, we can decide what elements to include into a hybrid model, which may be more feasible than going full force into DCTs, by incorporating patient participation thoughtfully, such as beginning with electronic consent forms.”

Ambery added that glucose monitoring is the poster child for patient participation in DCTs because it uses intuitive devices that patients adapt to quickly. As other user-friendly devices become available, DCTs can become genuinely patient-centric. Fox shared that patients also need options to participate in clinical trials fully; some are more comfortable in a doctor's office. Hybrid trials may be more amenable to these patients than fully decentralized trials. All panelists agreed that although DCTs add complications to clinical trials, their popularity will continue to grow, as will the technology built to support them.