Decentralized Clinical Trials - a pathway to more subjects and greater diversity?

In September, the FDA released its final guidance document on Decentralized Clinical Trials (DCTs). The FDA isn’t alone, as numerous geographies have released similar documents in recent years, including Denmark, Germany, Switzerland, and the European Medicines Agency, to name a few. Industry organizations and think tanks like the Association of Clinical Research Professionals have also provided guidance documents.

So why all the focus now? A couple of concurrent things have hit the industry simultaneously, leading to greater adoption of DCTs. For a while now, there has been the desire to decentralize trials to decrease cost and site burden, and then when COVID hit, that desire became a necessity for many trials. Luckily, several underutilized technologies allowed this sudden necessity to work for many trials. Since then, companies, sites, and regulatory agencies have accepted that DCTs can be run successfully and have a place in the industry.

One area in which DCTs may be beneficial is the implementation of Diversity Action Plans (DAPs), which I wrote about in a previous blog. DAPs will require studies to focus on and recruit populations that have historically been left out of studies primarily because they are far from research sites, cannot regularly travel for visits, and a number of other reasons associated with location and socio-economic restrictions. DCTs - whether entirely decentralized or hybrid - will make clinical trials more accessible to more people, allowing DAPs to be met and enrollment rates to be improved.

Whether a study is appropriate for complete or hybrid decentralization - or not decentralized - will depend on the drug and device. The FDA guidance addresses some of these considerations based mainly on safety. In short, complex devices or drugs with unknown safety profiles may still require the typical in-person visits, while other therapies will have a greater opportunity to decentralize.

Several important considerations with a DCT need to be addressed in the study protocol and operational execution. Since the requirements to ensure subject safety do not change with a DCT, the risk of missing safety events as subjects complete visits remotely or at other health care providers outside of the site will need to be carefully planned for. Protocols and study infrastructure will need to address this.

Sponsor and Site SOPs will likely need to be updated to address how DCTs are operationalized appropriately. This may seem like a small thing on the surface, but many of the ways we do clinical trials are deeply engrained, and it will take intentional effort to adjust the way we work to move to DCTs successfully. This includes but is not limited to, how remoted health care providers are contracted with and utilized, study budgets, use of digital tools, etc.

I touched on earlier how protocols and study plans are written, which will change significantly to take full advantage of DCTs while ensuring high-quality data at the end of the study. I looked at a recent study I ran, and with careful planning and adjustments to the protocol, the number of site visits by subjects could have been reduced by 30%. Undoubtedly, this would have increased our enrollment rate and decreased missing data. I also randomly looked at some older studies on CT.gov and came to a similar conclusion. Of course, some studies, such as device studies requiring regular re-programming or monitoring, would benefit less than a device readily used at home or requiring infrequent in-person review.

In summary, I believe all companies should examine whether and how they can decentralize components of their studies. If so, it may help with enrollment, meet diversity requirements, and improve the overall study data, leading to better-informed decisions and regulatory submissions. However, it needs to be accompanied by well-thought-out strategic plans.