Decentralized clinical trials (DCTs) came into their own in 2020 during the COVID-19 pandemic. Faced with unprecedented changes, clinical research teams had to adapt and continue vital research without traditional face-to-face trials. Clinical trials were conducted through a variety of methods, from in-home to local lab visits, using technology to complete many of the requirements.
Three years later, are decentralized trials here to stay or will we see clinical researchers go back to their traditional routes? In this article we’ll explore decentralized trials in depth, assessing their benefits and challenges, as well as what the future looks like for this type of trial.
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What are decentralized clinical trials (DCTs)?
According to the Food & Drug Administration (FDA), a DCT is “the decentralization of clinical trial operations where technology is used to communicate with study participants and collect data.” The trial’s activities would occur at locations other than the traditional clinical trial site. These locations could be the participant’s home, online, in a local healthcare facility, or at a nearby laboratory.
With rapid technology advancements and the need for flexibility, the decentralized clinical trial model removes the requirement for in-person contact between the participant and the research team.
A DCT often uses a hybrid model, where some trial elements have no in-person contact, and others are carried out traditionally. Many trials for drug approval already include decentralized aspects. For example, some research teams use video consultations for participant updates or side effect tracking.
What is the difference between decentralized and centralized clinical trials?
Centralized clinical trials are the traditional method of clinical trials. These trials have a central location. Participants visit this site for all aspects of the trial, from recruitment and registration to wound checking and side effect tracking. This differs from decentralized trials where there is no central location and participants may take part through a variety of mediums.
Another key difference between a decentralized clinical trial and a centralized clinical trial is technology. Decentralized trials rely on technology for keeping in touch with participants remotely and carrying out elements of the study. Centralized clinical trials usually only use technology to keep track of data.
Are decentralized clinical trials the same as virtual clinical trials?
While people use both terms synonymously, the definitions of decentralized and virtual clinical trials are different.
Virtual clinical trials are fully remote. This means there is either no or limited physical contact between participants and researchers. These trials use eConsent, telemedicine, remote patient monitoring, mobile health, wearables, and digital biomarkers.
Clinicians do everything remotely via technology in a virtual clinical trial. They communicate with patients virtually, record observations using direct data capture (DDC), and store the data using an Electronic Data Capture (EDC) system.
This is a clear distinction from DCTs which use a combination of face-to-face and virtual elements. Some trials may refer to themselves as fully remote decentralized clinical trials - in other words, a virtual trial.
Can decentralization be used for all clinical trials?
As DCTs incorporate both virtual and in-person activities, most clinical trials can use decentralization elements. As of 2022, 89% of sponsors used DCT methods in some of their studies.
Researchers should carefully assess the nature of their trial before determining which elements can be decentralized. For example, if a clinical trial has a greater need for intervention from a healthcare professional, it’s more likely to need more in-person elements.
Since the COVID-19 pandemic, significant technological advances have made it possible to carry out DCTs more frequently. Researchers can perform the following duties:
- Recruit participants online
- Receive samples remotely
- Capture and record data online
- Use video technology for participant communication
What are the benefits of decentralized clinical trials?
Decentralized clinical trials offer a variety of benefits for participants, researchers, and trial sponsors. From easier access for participants, to reduced costs and improved accuracy for clinicians, there’s a reason why DCTs have become so popular.
Reduced participant burden
One of the key challenges with clinical trials is recruiting participants, particularly those from diverse backgrounds. By offering decentralized elements with fewer site visits, a clinical trial can be opened up to a much wider pool of participants.
By enabling participants to report remotely or collect data via a wearable device or online consultation, a trial becomes much more convenient. Participants are more likely to want to be involved in the study. There could also be an option for necessary visits to take place in nearby labs or the participant’s home to further reduce the participant's burden.
Reminders or alerts can also be sent directly to the participant's mobile phone to remind them to take their medication, complete a task, or record results. Likewise, wearable technology or sensors will send data directly to clinicians, removing another step for the participant.
Improved compliance and retention
It has been reported that around 40% of clinical trial participants stop adhering to protocols 150 days into a trial. Using a decentralized trial model enables researchers to improve compliance and participant retention.
Technology has made it easier to track participants in DCT clinical research, which means clinicians can see which participants are missing tasks. This data helps them to identify participants who may need more support or further guidance in how they participate.
Keeping participants engaged is also critical for compliance and retention. DCTs are digitally convenient, which means researchers can send regular feedback or communicate with the participants, and also enable them to check their data so they can feel more involved.
Greater accuracy
While in-person centralized clinical trials allow researchers to take a deeper look into the participants’ side effects or data, they are limited in that this information is only available at the clinical trial site. This means participants who experience a change away from the clinical trial setting might be missed, rendering some results of the data invalid.
DCTs give patients the ability to record symptoms, side effects, or any other change in real-time via an app, online portal, or remote monitoring device. It has also been cited that home reporting is more accurate as it reflects the behavior of participants in their everyday environment.
Without the need for site visits and logistic organization, DCTs also allow for more frequent or continuous data collection. This results in greater volumes of and much more accurate data.
Quicker trial delivery
Decentralized clinical trials can speed up the trial process, from recruitment through to delivery. Research has found that DCTs have a 1.3 to 2 times faster enrollment rate than centralized clinical trials.
Data collection is much quicker in DCTs. Electronic patient reporting is easier than reporting on paper due to the notifications and reminders sent to patients to report on time.
Following trial completion, DCTs allow for faster data analysis. With all data collected via cloud-based Electronic Data Capture (EDC), all trial information is housed in one place. This enables researchers to manage and clean data in real-time, resulting in faster advancement in analysis.
Reduced cost
Digital Health Tools (DHTs) and remote participation naturally reduce costs in a clinical trial. Without a requirement for a brick-and-mortar study site or physical infrastructure for data collection, researchers can save a significant amount of money.
In decentralized trials, participants may not need to travel to a clinic site, which means clinical research teams can also save money on travel expenses. In addition, the digital nature of data collection in a DCT can offer a much more efficient and cost-effective trial process.
Increased access
Access to clinical trials has been cited as a key challenge in clinical trial recruitment. With decentralized clinical trials, there is less need for travel to clinical sites, resulting in a larger pool of potential participants. People living in rural areas or those who do not drive may find it easier to participate in a trial with remote elements.
Using DCTs to improve access is particularly beneficial for studies concerning rare diseases since clinical trials are often competing for the same limited pool of participants.
With more people able to take part in a DCT, researchers can also recruit participants from more diverse backgrounds. This is essential for improving diversity and inclusion in clinical trials and gaining a greater understanding of certain drugs or conditions.
Improved participant safety
With real-time reporting, researchers can improve participant safety by tracking behaviors as they occur. For example, if a subject has an adverse reaction to medication, they can be alerted instantly and take steps to monitor or intervene.
Long-term follow-up
Many clinical trials require long-term follow-ups to track their effectiveness and identify long-term safety issues. By using the decentralized model, research teams can stay in touch with participants more easily, without relying on in-person contact or on-site facilities.
What are the challenges with decentralized clinical trials?
Just as there are many benefits of DCTs, there are also a few challenges. From industry regulations to risk aversion and access, many researchers will stumble upon challenges when implementing the DCT model.
Regulations
Centralized clinical trials have been the norm for a long time, and it was only really the COVID-19 pandemic that accelerated the need for decentralized elements in clinical trials. Because of this, governments have been reluctant to change regulations to showcase the use and benefits of decentralized clinical trials.
The European Medicines Agency (EMA), for example, permitted some DCT elements during the COVID-19 pandemic, albeit temporarily. In the United States, however, FDA guidance has been more accepting of digitization in clinical trials.
Systems integration
Digital innovation is difficult to implement overnight. With DCTs, depending on the elements, research teams may need to introduce several different systems or tools. This can be both expensive and time-consuming.
Some teams may already have a variety of digital tools in place which need to integrate with newer tools. This may be impossible for some pieces of technology, while others require technological upgrades for a successful integration, which again can take time and money.
Risk aversion
For many research teams and clinicians, using DCT models is a completely new way of working. Some teams may be more hesitant or risk-averse when asked to implement the DCT model or use technology. They might feel anxious as it involves a significant change in what they are used to.
Equally, if technology has been integrated unsuccessfully or staff have not been given sufficient training, this could result in even greater resistance to change. Research teams must reassure staff that transitioning to DCTs is beneficial and will be managed effectively and carefully.
Accessibility
While improved access is a key benefit of decentralized clinical trials, it can also be a disadvantage. Since DCTs rely on technology, those without internet access or those who are less tech-savvy could be restricted from participating. The key to successful decentralized clinical research is choice and a hybrid approach, whereby participants have greater control over how they participate.
How to successfully implement decentralized clinical trials
Successful implementation of decentralized clinical trials is essential for this model to work. There are several things research teams can do to ensure DCTs are implemented effectively, from ensuring the right technology is available, to mitigating potential risks.
Get the right technology
We’ve already mentioned how important technology is when it comes to DCTs, but it is key to a successful implementation. Whether it involves wearable devices, telemedicine, or digital data collection, researchers must ensure the technology or digital tool they choose is fit for purpose.
Validate digital endpoints
Digital endpoints refer to the clinical outcomes gathered from decentralized aspects of a clinical trial. Some examples are measuring participants’ heart rates to provide an endpoint for heart failure or using data from continuous glucose level monitoring to provide endpoints for time-in-range or hypoglycemia. Ensuring these endpoints are validated and recorded properly is essential for recording accurate data.
Enable (not replace) clinical professionals
While it’s easy to think DCTs remove the need for clinicians , the opposite is true when trying to successfully implement them. Instead of giving all responsibility to the participants, clinicians should be empowered and able to support participants on a remote basis. This could come in the form of additional training in new technology, new job roles related to the digitization of the trial, or opportunities for home visits.
Risk mitigation
Every clinical trial comes with risks and DCTs are no exception. However, the risks of DCTs usually differ from traditional trial settings. For example, researchers need to ensure any technology they are using has “after hours” technical support if devices stop working. Likewise, replacement devices need to be readily available.
Participant training adaptation
When using the DCT method, more responsibility is naturally placed on the participants to complete their tasks without regular in-person support. It’s therefore vital that participants know exactly what they should be doing, and how.
Researchers need to ensure participants have had thorough training and education before the trial starts. This should also continue throughout the trial, using reminders from a variety of mediums to keep participants engaged.
Prioritize participant engagement
Without regular face-to-face contact, some participants could lose interest in the trial, leading to missed tasks or inaccurate data. It’s therefore key for research teams to maximize the ways they keep participants motivated to continue.
There should be regular remote contact with participants to keep them engaged in the trial. For example, researchers could send newsletter updates, video messages, puzzles, or quizzes as part of their regular communications.
Simplify study designs
Decentralized clinical trials offer an opportunity to change the format of a trial and simplify it to suit everyone. Research teams should avoid tasks that place extra burden on the participants. If the task is not an integral part of the study or will not provide essential data, don’t include it.
Encourage post-trial engagement
Participants have different motivations for joining a clinical trial, but once the trial is finished, it becomes harder to keep them engaged for future trials or further research. Throughout the trial, researchers should stay in regular contact with the participants, offering them more opportunities to be involved in the current and other research projects.
Decentralized clinical trial examples
As decentralized trials continue to gain traction in the industry, we’re seeing more examples of them being completed successfully. In 2022, several big clinical trial players adopted the DCT method more frequently. Takeda Pharmaceuticals, for example, decentralized 33% of its clinical trials, while Bayer decentralized 22% of its trials.
Many pharmaceutical companies are using DCTs for the benefits they provide to participants. DCTs are also favored by Contract Research Organizations (CROs), which means researchers can usually access more funding.
COVID-19
We’ve already mentioned COVID-19, simply because it was a huge driving force for the adoption of DCTs. Without decentralization, trials already underway would have ground to a halt and new trials wouldn’t have started. This could have been detrimental to studies related to COVID-19 vaccines.
A study by Biomed Central found that all clinical research organizations, and members of the public-private “Trials@Home” consortium, were already using some decentralized elements in their studies before the pandemic. However, 83% implemented decentralized methods as mitigation for COVID-19. Furthermore, many respondents expected to maintain decentralization in ongoing and future trials.
Infant formula safety and tolerability
Decentralized clinical trials have also been used for research concerning infants. It’s notoriously difficult to recruit babies and infants for interventional clinical trials, so this group has been key for measuring DCT success.
Decentralization naturally recruits more willing participants, and with digital tools, it’s possible to record accurate infant health observations while reducing subjectivity.
For example, rather than asking participant caregivers to score their babies' rashes on a quantitative scale, technology can be used to guide caregivers through the process of taking photos or videos directly from their devices. This method offers more qualitative data that presents more accurate and useful results.
Other successful uses of digital health technologies as used in DCTs
Another successful use of digital health technology similar to those used in DCTs involves home blood pressure monitors. These devices enable people with hypertension to improve their self-management of their condition, resulting in a reduced risk of cardiovascular disease or death over time. Insulin pumps and blood glucose monitors also use similar technology, providing diabetics with accurate information that can be used for self-medication of insulin when the glucose is too high.
Is the health industry reluctant to embrace decentralization?
While decentralization has previously been slow in terms of uptake, things are changing and regulators appear to be more willing to support DCT. In 2023, the Accelerating Clinical Trials in the EU Act is placing a special focus on DCTs, aiming to facilitate innovative clinical trial methods.
Clinical trial sponsors are keen to embrace decentralization too. Six out of ten sponsors that used decentralized trial elements in 2022 were based in Europe. The United States had previously led the charge in decentralization uptake to improve diversity, but it appears that Europe is catching up.
Some clinicians have been hesitant to support decentralization, for reasons including a lack of understanding, assumed greater risk, and thoughts that DCTs were being implemented for the wrong reasons.
However, with decentralization guidance coming from the European Medicines Agency (EMA), the European Commission (EC), and Heads of Medicines Agencies (HMA), more clinicians are supporting DCTs.
The future of decentralized clinical trials
DCTs are still gaining traction, and advancements in technology and data analysis will continue to shape their future. In 2022, DCTs grew significantly, with 40-45% of studies using decentralization.
Participants are on board too. One study found that 78% of participants preferred a decentralized trial to a traditional site-based one. The same study also revealed that 89% of patients who chose the decentralized method completed the study, while only 60% of those who chose the traditional method completed it.
Some organizations are still learning though, posing questions surrounding the scalability of DCTs, incorporating the patient voice, and which Key Performance Indicators (KPIs) should be defined. Each of these issues will need to be addressed before we see widespread adoption of DCTs.
Conclusion
So are decentralized clinical trials here to stay? With the advancements in technology, increased positive attitudes towards DCTs, and support from organizations, we think DCTs are here for the long haul.
We don’t expect to see fully decentralized or virtual trials any time soon. As more pharmaceutical companies begin to understand decentralization, its benefits, and how it can be used safely in their own trials, we expect to see greater inclusion of decentralized elements or hybrid trials in the future.