January 31 2023 Andrew Park, Pharm D.

Decentralized clinical trials (DCT) seems to have burst on to the scene in just the last few years, so it is easy to get swept up into how we can best implement them into our clinical trials. However, it is worth examining the past of this supposedly “new” method of conducting clinical trials.

DCT is not a singular method, but a collection of tools and strategies which allow a robust clinical trial to be conducted, either in whole or in part, without study participants having to come to a hospital or clinic for all study related assessments. These tools include, but are not limited to, electronic consent, digital health technologies, telemedicine visits, home visits by nurses, and blood work done by a local lab. It is apparent that some of these methodologies have been around for many years; the main thrust of DCT is implementing these existing tools in the context of clinical trials.

Even the “modern” implementation of DCT is likely older than we think. The first fully virtual study was Pfizer’s Research on Electronic Monitoring of Overactive Bladder Treatment (REMOTE) conducted in 2011, more than a decade ago. Prior to that, there were other studies that implemented some components of DCT. One such study was Lilly’s 2002 Magellan study, a phase III study of tadalafil in 80 subjects conducted using electronic consent, remote safety and efficacy monitoring, home shipment of study drug, and electronically reported patient outcomes.  That is almost hard to believe considering the study predated the first iPhone by about 5 years.

Obviously, the march of technology (near ubiquitous internet access, proliferation of smartphones and wearables) has greatly contributed to the advancement of DCT and its associated tools. However, there is also a regulatory dimension to DCTs, and the argument can be made that the start of it all is was the introduction of 21 CFR Part 11 in 1997.  This introduced the standards for acceptable electronic records used for clinical trials and is foundational for electronic tools and records that are accurate, traceable and verifiable. It is hard to imagine that DCT could be meaningfully implemented without Part 11.

Since then, the FDA has generated some additional guidance that touch upon electronic records and DCT including the 2009 guidance, Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims which devoted an entire section to electronic PRO instruments. That said, the strongest impetus driving studies in the direction of DCT came not from a regulatory body or the pharmaceutical industry, but from a virus.

“Even the “modern” implementation of DCT is likely older than we think.”

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In 2020, the SARS-CoV2 pandemic made the conduct of traditional, centralized clinical trials nearly impossible in the span of days. With few other options, many sponsors turned to DCT solutions to continue ongoing studies and get studies in start-up off the ground. To provide guidance during this chaotic period, both the FDA and EMA published guidance documents in 2020 on conduct of clinical trials (with updates following through 2021 and 2022). These guidance documents included an emphasis on DCT strategies such as e-consent, telemedicine, home shipment of study drug, and others. Also passed in response to the COVID-19 pandemic was the CARES act of 2020, a key provision of which was parity of reimbursement for telemedicine visits as compared to in-person visits. Since costs of standard of care visits are often to be covered by a patient’s insurance in a clinical trial, this removed an important hurdle for patient participation.

These were excellent steps toward bringing DCT into the clinical trial mainstream. However, it is important to note that the guidance documents noted above and the telemedicine reimbursement parity are indicated to expire once the COVID-19 related public health emergency is over. There certainly is no putting the cat in the bag now, but for DCT uptake to continue in a reasonable manner after the pandemic is over, a continued dialogue between regulators, investigators, patients and industry will be needed.

That said, we are not out of the pandemic yet, so where do things stand with DCT today? What are its benefits, and what are the challenges associated with implementation. Has the wave of DCT studies (both fully virtual and hybrid) produced all its promised benefits?  This is something we will explore in part 2 of this blog series.

PROMETRIKA hosted a live webcast about “Exploring the Impact of Decentralized Clinical Trials”. To learn more, we invite you to watch the video here.