How the History of DCTs Impacts Today’s Trials

Decentralized clinical trials (DCTs) and those with hybrid elements have increased substantially and shifted the research landscape. Within the U.S., 12.1% of clinical trials from 2019 to present incorporated decentralized elements, compared to 3.3% from 2010 to 2016.?

Although adoption of DCTs was undoubtedly catalyzed by necessity during the COVID-19 pandemic, the roots of this shift are deeper. Decentralization reflects evolutions in the industry’s approach to efficiency, participant engagement, and accessibility. Charting the rise of DCTs provides key insights into their appeal, as well as lessons that can inform further advancements.??

The First Decentralized Clinical Trials

The first fully virtual trial was likely Pfizer’s Research of Electronic Monitoring of Overactive Bladder Treatment (REMOTE) in 2011, but this was not the first use of decentralized elements. Hybrid trials began even earlier. One of these was Eli Lilly’s 2002 study for tadalafil for treatment of erectile dysfunction. These studies offered privacy and the potential to reduce stigma for patients, highlighting benefits that continue to apply to DCTs today.??

Some of the common decentralized elements in decentralized and hybrid research during this time included:?

• Electronic consent?
• Remote monitoring?
• Electronically reported patient outcomes (ePROs)?
• Telemedicine?

These technologies were addressed in early FDA guidance surrounding decentralization, such as 21 CFR Part 11. Released in 1993 and updated in 2003, this covers requirements for electronic records. ePRO requirements from the FDA were released in 2009.??

This initial interest in decentralization may, over time, have been enough to result in the rise of these technologies, independent of other shifts. However, the rapid adoption of decentralized technology was largely due to external circumstances: the COVID-19 pandemic.??

Evolution Driven by Necessity??

As the pandemic forced research sites to close, a rapid pivot became necessary to maintain trial continuity. The widespread solution was decentralization. In one survey, 38% of respondents expected virtual trials to be a major component of their portfolios in December 2019. A year later, in the midst of the pandemic, this portion jumped to 100%.??

At the pandemic’s peak, the industry integrated decentralization into protocols that did not previously plan for this approach wherever possible. In particular, remote visits through telemedicine grew rapidly, as compared to more modest approaches to decentralization like digital data collection that were gaining traction prior to the pandemic. Adoption of DCTs was comprehensive across trials’ timelines and protocols, and it was also rapid and driven by necessity.??

The speed of decentralization in the face of site closures required a correspondingly quick regulatory response. The FDA released guidance in March 2020, a rapid response to the urgent circumstances. Although the original documents were only intended to remain in effect during the duration of the public health emergency, initial releases and discussions have continued to inform ongoing draft guidance. Refinement of these requirements is a continual process.??

Toward a Balanced Approach?

As restrictions on physical sites have been lifted and the immediate crisis of the pandemic has passed, the research industry is now faced with integrating lessons learned and forging a path forward.?

Adoption of DCTs demonstrated significant value, from greater flexibility for sponsors to improved access for patients who live further from traditional sites or simply prefer to save time by participating from home. This has led many sponsors to continue a fully or heavily virtual approach. Others have realized limitations around monitoring requirements or participant familiarity with technology, resulting in a return to brick-and-mortar trials. However, most approaches fall between these two extremes.??

Now that DCTs are no longer a strict necessity, the industry has a pivotal opportunity to thoughtfully implement decentralized elements. The key is finding solutions that are specific to each trial’s needs.?

Some factors to consider include:??

• How does decentralization affect access for your trial’s demographic? For example, patients living further from trial sites may be able to participate more easily and conveniently through telemedicine. Conversely, rural populations may not have access to the technology required.??
• What level of monitoring is necessary for patient safety? Keep in mind that even if one-on-one care or close monitoring is required for treatment administration, follow-up visits could still be conducted remotely depending on the circumstances.?
• How could decentralization improve the experience for your research teams, and do they foresee any challenges you need to address? Everyone involved in your trial contributes to its success, and understanding what your teams think about decentralization is helpful. They may be able to point out challenges that decentralization could solve or may notice issues that need to be handled proactively.??

Support for Your Decentralized or Hybrid Trial??

Whether you are running a fully remote trial or taking a hybrid approach, participant welfare and regulatory compliance are crucial considerations. Choosing an institutional review board (IRB) with experience in decentralized research gives you access to a wealth of expertise to address your questions throughout the process. Sterling IRB provides full-service solutions with a personalized approach, backed by an extensive background in DCTs and hybrid trials. We are dedicated to safeguarding your research.??

Contact us to explore our IRB services for decentralized and hybrid clinical trials.?