Kristin Mauri

Decentralized Clinical Trials Are Here to Stay

By Kristin Mauri, Director of Solution Services, Remarque Systems

The popularity of decentralized clinical trials (DCTs) is surging — especially among patients. Harnessing technology of all kinds, these trials provide an attractive alternative to the old-style, site-anchored system on which traditional clinical trials have rested. They also have the potential to provide better, more timely data since that data is primarily collected under real-life situations and often available more quickly to monitoring teams. With patients insisting on the convenience and control DCTs give them, there is a growing imperative for researchers to adopt new data management methods. Fortunately, technology holds an answer there, too.

The advent of DCTs

Over the millennia, trial designs have evolved. Basket trials test the same treatment against multiple disease states; umbrella trials evaluate multiple therapies against a single disease. Parallel trials, cross-over trials, and sequential trials all have found their place. And in 2011, what is thought to be the first decentralized clinical trial for an FDA-approved pharmaceutical used digital technologies to recruit and manage trial participants entirely from their homes.

There are many variations on these DCTs — often termed “virtual” or “remote.” In general, they are united by a decreased reliance on an intermediary and a physical location — instead, relying on software-driven tools to manage clinically validated patient data. Of course, DCTs also create some concerns; new methods require new protocols, tools, and approaches. Sites have wondered how they fit into the picture; researchers have wondered how to validate the data. Uptake has been gradual. Then the pandemic appeared.

Setting the stage for growth

As the pandemic raged, people around the world were advised to stay home — and, especially, to stay away from hospitals, clinics, and other places where the infected may be seeking care. Most complied without hesitation. This was particularly true for people in clinical trials; no one already immunocompromised or suffering from other pre-existing illness wanted to risk exposing themselves to a deadly disease with no cure and only limited treatment options.

Many decided to forgo both routine care and necessary tests and treatments. Experimental treatments fell to the bottom of the list. Clinical trials everywhere ground to a halt. The industry scrambled for solutions. Then one became apparent.

In a bid to maintain momentum, sponsors and contract research organizations (CROs) realized they could offer patients a safer option. Instead of potentially exposing their trial participants to COVID during travel and site visits, they could pivot to DCTs, dispensing treatments and collecting data while largely leaving patients in the safety of their own homes. Regulatory bodies helped by relaxing some of the guidelines around data verification. Clinical trials started again.

Patients prefer DCTs. Sponsors may too.

More than 70 percent of potential clinical trial participants live two or more hours away from the nearest clinical trial site. So, no wonder patients were relieved when the trial came to them — and they are resisting reverting to traditional site-based trials.

Indeed, DCTs are shown to improve recruitment, retention, and compliance. Further, the often-continuous stream of data collected in a natural setting may paint a more insightful picture of a drug’s efficacy than data collected at set time-points. Ultimately, DCTs may amplify study efficacy, shortening time to market — and, in the process, saving patients’ lives and sponsors’ money.

Before that can happen, however, researchers need to master all that data. Again, technology can help.

Technology makes it possible: trial management platforms

Fitness trackers. Smart watches. Skin patches. Blood pressure monitors and pulse oximeters you purchase at the corner drugstore. Every day, it seems, some new technology, once requiring enormous infrastructure and technical oversight, is now readily available to the masses. Throughout the past decade, the explosion of mHealth technologies has helped make DCTs possible; concomitantly, telemedicine (bolstered by visiting research nurses) can replace many of the site visits themselves. Yet, the promise (reams of real-life data) also contains significant challenges (reams of real-life data). Traditional data management and point-by-point source data verification are impractical.

Sponsors need a robust clinical trial management system to monitor and manage their trials efficiently and effectively. Fortunately, technological solutions can collect, organize, analyze, and help verify all the data from a DCT. Here are some key features sponsors should look for:

  • Data collection.  The first step in data management is to centralize all the data. Look for a system or platform that can collect data from apps, wearables, home-monitoring devices, and other mHealth applications, as well as lab tests and more traditional data sources.
  • Data harmonization.  Before you can analyze the data, you will need to harmonize it to enable apple-to-apple comparisons.
  • Detailed data interrogation. Data collected remotely requires the same close examination as data collected on-site. Seek a system with dynamic drill-down capabilities that enable you to interrogate any source data of concern.
  • Process-calculated metrics. One effective solution to managing robust amounts of data is to monitor based on risk. The optimal platform offers flexibility in setting user-defined metrics for analyses that are relevant and actionable.
  • Machine learning capabilities. Machine learning enables systems to quickly analyze data and provide near-real-time insights, thus supporting many key aspects of risk-based monitoring.
  • Built-in audit trail. Regulators require proof of monitoring — including any anomalies identified and subsequent steps taken. Choose a system that delivers the audit trail automatically.
  • 21 CFR Part 11 compliancy. Since 1997, this has been considered one of the most important regulations affecting drug development, guiding the FDA’s approach to processes such as validation, audit trails, and records. Any platform or system you choose should be compliant.
  • Self-sufficiency. The ideal platform enables independent system setup and use. You should have access to vendor support when you need it — but not require their services continually for the system to work.

Why DCTs are the future of clinical trials

Today, less than five percent of the U.S. population participates in clinical research. One key reason: traveling to a clinical trial site is burdensome. During the pandemic, it has been potentially dangerous. It can also be expensive, possibly even incurring lost wages or requiring that childcare/eldercare be hired. These drawbacks limit initial interest and lead to attrition as a trial progresses. DCTs provide a simple solution: bring the trial to the patient.

After the increasing adoption of DCTs during and since the early days of the pandemic, patients are clear that this is the route they choose. Thus, going forward, effective recruitment and retention will increasingly depend on the convenience DCTs offer.

Fortunately, DCTs offer striking benefits for sponsors, too: the promise of more effective data collection. Increasingly sensitive measurements from digital technologies coupled with a new density of data — continually measured under real-world circumstances instead of quarterly in a clinical setting — can help researchers understand efficacy sooner.

Yes, managing and monitoring all that data requires new approaches and new technology. However, that technology exists: the ability to collect, analyze, and monitor reams of data in near real time. It paves the way for the sustained rise in DCTs, amplifying study effectiveness, enabling drugs to get to market faster, saving sponsors time and money — and most importantly, speeding new therapies to patients who desperately need them.