Introduction

Beginning at the turn of the 21st century, the life sciences industry began to envision a different way to conduct clinical trials. The rise of technology such as electronic data capture (EDC) helped pave the way for the first electronic clinical trial systems. And in the coming years, electronic clinical outcome assessments (eCOA) and electronic informed consent (eConsent) would be pioneered across the industry for the first time. 

Then in 2011, Pfizer cast the first true stone towards decentralization, conducting the first-ever “virtual” clinical trial. 

Now, one year after the COVID-19 pandemic the era of decentralization appears to be here. In fact, a late 2020 survey by Oracle Life Sciences highlights that we’re at the tipping point, with 76% of surveyed trial organizations investing in decentralized clinical trials (DCT’s).

At Medable, we’ve conducted over 100 decentralized clinical trials with over 1 million patients on our platform. As pioneers of decentralized trials, we help clients deploy solutions that meet the best needs of their patients and protocols, no matter where they’re located. In 2020 alone, we helped dozens of study teams transfer in-progress on-site clinical trials to decentralized models, in just weeks. 

Thus, in this guide, we’ll explore the ins and outs of decentralized clinical trials in an effort to lead you to better and more informed decisions about your clinical trial future. 


What is a Decentralized Clinical Trial (DCT)?

The FDA defines decentralized clinical trials as “those executed through telemedicine and mobile/local healthcare providers, using processes and technologies that differ from the traditional clinical trial model.”

Generally, these trials are conducted remotely instead of at a site facility, with patients remaining at home during most of the trial. Here, interactions with sites take place using software, phone applications, connected devices. These tools feed sites and sponsors crucial trial data while providing face-to-face connections with investigators through technology.

Decentralized trials are sometimes often known by other names, these include; remote trials, virtual trials, and siteless clinical trials. However, not all of these names are accurate, as DCTs can often involve sites and other facilities.



How a Decentralized Trial Differs from a Traditional Clinical Trial

The NIH defines a clinical trial as “A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.”

In traditional clinical trials, the patient must come on-site to a facility where they will be screened, consented, and possibly enrolled. Once enrolled, the interactions between the patient and those who run the trial will continue on-site.

In a decentralized trial, there are more options for interactions. Here, any one of the above touchpoints can be offered remotely, using technology. The result is a potent and powerful blend that enables flexibility in trial design. 

For instance, let’s picture an eczema trial. Here, sponsors and investigators may still believe an initial on-site screening is necessary. However, they may not believe that follow-up appointments must be held on-site. As a result, the trial organizer provides patients with technology to upload their progress after the initial visit and connect with the site. In this instance, the organizer employs a telehealth solution in order to keep the face-to-face rapport of an in-person visit and to transmit images to a remote investigator. 


The Different Types of Decentralized Clinical Trials (DCTs)

Hybrid: In a hybrid decentralized trial, participants may come on-site for some trial activities, such as screening and enrollment, while completing the rest of the trial at home or remotely. 

Fully-remote: Here, every aspect of the trial is handled remotely with the trial organizer working with sites, direct to patient shipping teams, care nurses, and more to ensure the trial is run smoothly without the patient ever needing to leave home. 


Tools and Services Employed in a Decentralized Trial 

  • Telemedicine
  • eConsent
  • Home Health Coordination and Management
  • Centralized Data Collection 
  • Mobile Devices and Wearables (eCOA, ePRO, etc.)
  • Patient Interactive Portals
  • IP and Study Supply Logistics


TeleMedicine/televisits:

Televisits bring the experience of an in-office visit to the comfort of a patient’s home. Televisits are a descendent of the larger term, telehealth.

The HHS defines telehealth as “Telehealth — sometimes called telemedicine — is the use of electronic information and telecommunication technologies to provide care when you and the doctor are not in the same place at the same time.”

In a decentralized setting, televisits are a two-way video call between the site investigator and the patient that takes the place of an in-person office visit, while enabling them to keep the rapport of face-to-face interactions.



Related Blog: RECOMMENDATIONS FOR OPTIMIZING TELEVISITS


eConsent

According to the FDA, informed consent “involves providing a potential participant with: adequate information to allow for an informed decision about participation in the clinical investigation. facilitating the potential participant's understanding of the information.”

eConsent is an electronic version of the informed consent process. But, the key difference here is that the electronic format allows for custom tailoring of the trial information to the trial’s demographics. This information tailoring is presented using images, video, audio, sound, quizzes, and more. 

Additionally, eConsent enables study participants to consent to the trial, no matter their location. This is key in a decentralized setting, where office visits are limited or removed from the trial design entirely.



Home Health Coordination and Management

Home health coordination embodies the phrase “placing the patient at the center of care.”

In a traditional clinical trial, patients visit the clinical trial site to complete trial activities and receive services such as drug administration, collection of patient information and samples, and other services. 

However, in a decentralized setting, licensed healthcare providers render services in a patients home, eliminating the need for travel and greatly reducing burden. 

Home health coordination is extremely beneficial in trials that are caregiver intense, or are for rare diseases. 


Data Collection

Ironically enough, centralized data collection is one of the defining features of a decentralized system. 

In a typical decentralized trial, tools and platforms request, collect and share data using a single master “data architecture” that not only works across systems but is frequently integrated with other clinical systems such as EDC. 

This is key, as it eliminates one of the largest problems typically seen in traditional trial settings, data siloization.


Mobile Devices and Wearables (eCOA, ePRO, etc.)

Mobile devices are either patient-owned or study-supplied devices that consist of smartphones, tablets, etc. These are used by patients to navigate their trial’s application/portal, enter in data regarding their trial’s progression (in diaries or journals), and engage with healthcare providers through televisits.

Wearables are devices such as smartwatches, scales, blood glucose monitors, and more that allow continuous physical monitoring of the trial patient. With wearables, data is collected and sent automatically to sites and study teams for patient monitoring and outreach.

Related Blogs: THE LANGUAGE OF eCOAS & I WANT TO TELL YOU IN MY OWN WORDS: PATIENT REPORTED OUTCOMES


Patient Interactive Portals or Applications

These are mobile or internet-based applications that allow the patient to engage with their trial. Here, these serve as the main interaction point between the patient and the site. Patients can use these to book visits, consent, ask questions, book or engage in a telehealth visit, and more. 

IP and Study Supply Logistics

These are the services that provide patients with the study drugs and supplies they need in order to participate in the trial remotely. 

They are often sent to patients’ homes through a third-party vendor who is able to meet all of the study drugs’ needs (I.E. cold shipping). 

In some instances, trial drugs and supplies are provided to the patient through home healthcare services. Here, the home healthcare aid arrives with the study drug and supplies and administers it at the patient’s home. 



Typical Decentralized Trial Flow





Why Decentralized Trials are the Future: Their Benefits

Decentralized clinical trials are seen as the final destination for the industry, due to a number of reasons. Chief among these is their ability to put the patient at the center of a clinical trial without disrupting their life.

However, there are numerous reasons and benefits why decentralization is the future. 


Patient Benefit: Increased Patient Access and Less Burden

Currently, there are a number of problems that prohibit many types of people from participating in clinical trials. As CISCRP research shows, 87% of persons surveyed about clinical trials are “eager to participate in relevant clinical trials.” Yet, the same research shows that 70% of those surveyed live greater than two hours away from their nearest research site.

In a decentralized model, the patient's own residence becomes the center for research, removing site access from the equation and eliminating the problem. The benefit here for both patients and sponsors is that the trial now has theoretical access to 100% of the patient population. Whereas in a traditional setting, patients must be within travel distance to the clinical trial site in order to participate. 

Related Blog:: BIAS AND DECENTRALIZED TRIALS: HOW TO AVOID SELECTION BIAS THROUGH PROACTIVE ACTION



Patient Benefit: Fits Into Patients Daily Lives

For many, traditional clinical trials can often disrupt their normal lives. Travel times, scheduling around visits, arranging transportation, coordinating with caregivers and more are all additional efforts that many patients will encounter during the life of a trial.

In a decentralized setting, the patient remains at the heart of the trial. Thus, services are built around fitting into their daily lives. While we’ve already covered travel, and it’s relation to patient access, 

As Medable PAC member Paul Kidwell states in this blog (video #3 on sacrifice), “I would have to bank in three hours for back and forth, parking, appointments, and traffic for appointments. Looking at it, that’s three hours that I can’t personally bill.”

In fact, “a Harvard School of Medicine study, in fact, showed that an in-person doctor visit in the U.S. takes about 121 minutes – and only 20 minutes of that time is spent face-to-face with a doctor.” - Opportunity Costs of Ambulatory Medical Care in the United States



Patient Benefit: Increased Patient Education and Retention

In a decentralized trial, patients are provided with an app that is used as the “single source of truth.” This is important, as surveys show patients prefer a single touch point when engaging with their trial. 

Within the app, patients gain access to generalized healthcare information and education about their condition, the ability to view or schedule upcoming trial activities and televisits/virtual appointments, the ability to engage with investigators at any point, and are provided with answers to frequently asked questions and other resources which improve the likelihood of patients remaining in studies. 

Put simply, an educated patient is a patient retained.



Sponsor and Patient Benefit: Improved Safety and Efficacy

Because decentralized clinical trials are often able to capture information in real-time, sites and investigators are armed with live, accurate windows into the progression of their trial patients. 

This information is key, as it’s often used to set safety thresholds and alerts that cause sites and investigators to reach out to patients whose datasets show signs of potential safety and efficacy issues. 


Sponsor Benefit: Increased Speed to Trial

Decentralized trials benefit from an increased speed to trial as a direct result of increased patient access. Why? With geography removed from the equation, larger patient pools make it easier to find potential patients who trial standards. 


Sponsor Benefit: Increased Data Accuracy and Standardization

Decentralized platforms often utilize a unified set of data standards when asking patients and sites to complete actions. 

While this sounds small in theory, disparate data sets are one of the larger problems of the industry.

Organizations who use multiple point solutions will often find themselves in a situation where manual data cleaning is needed in order to “de-silo” the data and present one clear picture of their trial. 

While this certainly is achievable, any organization that’s gone down this path will be quick to tell you that data cleaning is inefficient, prone to errors, and time-consuming. The result of this is often high costs.

However, there’s also a patient component here. As mentioned above, one of the key benefits of decentralization is a real-time window into the patients’ safety and efficacy. This window of opportunity is lost when data must be cleaned and assembled. 


Sponsor and Site Benefit: Unified Workflows

When properly designed, decentralized systems present their users with an intuitive, simple, and streamlined interface. The result is ease of use, which is key for patients who are looking for a single seamless experience.

However, it’s paramount for sites, who lose precious time bouncing between disparate systems and interfaces. As SCRS and Oracle’s research states: 

“More than a third of respondents expressed dissatisfaction with current eClinical technologies, which represents a 65% increase from 2016. Too many systems with different processes and login credentials, combined with redundant training, was cited as the main cause of this negative sentiment. Also, not surprisingly, dissatisfaction was found to be higher for sites working with multiple sponsors/CROs that require separate systems and login credentials. “



Sponsor, Site and Patient Benefit: Boost Communication Between All Parties

By nature of their design, decentralized systems can easily increase the amount of communications that take place between patients and sites, and sites and study teams. 

For instance, many decentralized systems, such as Medable’s, offer televisit functionality. This is key in connecting patients with investigators when they really need it. Take for example a patient who may be completing their electronic consent document. A patient who has the ability to quickly start or schedule a televisit with their investigator has a better chance of proper education and retention regarding the needs of the trial.