The rise of decentralized clinical trials
Starting in the early 2000s, 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.
In 2011, Pfizer took the first step toward decentralization, conducting the first-ever “virtual” clinical trial.
Today, digital and decentralized trial components have become common in clinical drug development.
Medable has enabled over 300+ decentralized clinical trials with more than 1 million patients on our platform. As pioneers of decentralized trials, we help clients deploy solutions that best meet the needs of their protocols as well as their patients, no matter where they are located.
Defining decentralized clinical trials (DCTs)
A traditional clinical trial is where researchers test a new treatment on a group of people, usually at a single location, like a hospital or research center.
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.”
In a decentralized clinical trial, part or all of the protocol occurs away from the primary study site. Instead of patients traveling, often repeatedly, to a central site for enrollment, consent, data collection or symptom monitoring, they can participate in telehealth visits from their homes, often using familiar technologies, like smartphones, tablets and wearables to transmit pertinent information. Even medications and devices can increasingly be delivered directly to a patient’s home, and a home visit from a health care professional can be arranged if necessary.
Though DCTs were first pioneered a decade ago, the advent of the COVID-19 pandemic catalyzed their use. Stay-at-home orders and, later, social distancing requirements, meant that study teams and participants alike could not effectively participate in on-site trials. In addition, technological advancements have created the Internet of Things (IoT), in which numerous devices, including wearables like fitness trackers, can all be connected through software and cloud computing. This enables seamless transmission of data of almost any kind.
DCTs, also known as virtual, remote or digital clinical trials, can easily be customized to the therapy, patient population or condition being studied. In fact, clinical trials can be fully decentralized or employ a hybrid model of virtual and in-person procedures.
In a fully-decentralized trial, every aspect from recruitment to treatment to data retrieval and analysis is done remotely.
In a hybrid trial, some of these steps will involve face-to-face or on-site interaction. Some trials, such as those that require frequent or complex imaging or surgical procedures, may be better suited for hybrid designs.
Tools and Services Employed in a DCT
Study teams can select which digital tools make the most sense to employ in their clinical trials; there’s no need to implement them all at once, or even to use the same ones in different trials. Digital tools offer complete flexibility, as well as familiarity, since they can run on smartphones, tablets, or any other device you choose. These are the most common:
Telemedicine enables clinical research staff to visit with trial participants remotely, through cell phones, computers, tablets, etc.
Virtual visits between patients and physicians help keep patients engaged and improve adherence to both the study schedule and dosing. With video-based televisits and interactive chat features, patients can consult with their physicians without leaving their homes, and physicians can easily monitor symptoms and health data. This results in greater peace of mind for patients and physicians alike.
eConsent is an electronic version of the informed consent process which enables trial participants to consent either on-site or remotely. Using video and interactive graphics, patients can learn more about the intent of the study, see how a drug or device is designed to work, better understand what is expected of them, as well as any risks participation may pose, and be kept appraised of any safety updates — all in less time than using traditional methods.
As eConsent has become more popular, myths and misinformation around its use have cropped up. Explore the truth around eConsent, and reach a deeper understanding of decentralized clinical trials here.
eConsent enables organizations to customize consent workflows around the needs of your study, and they can even enable connections to physicians or other health care providers as necessary. Lastly, many robust eConsent systems, including Medable’s, also provide wet-ink functionality in countries that require it, bringing the benefits of eConsent to countries that often rely on paper to properly inform participants.
With remote screening, patients can be screened and enrolled with just a few clicks, using any device, anywhere. Screening modules can be customized to the specific needs of a study, and can allow data collection from almost any source and in any format, whether that’s a medical image, blood work, or an EKG.
Read more: Where does patient recruitment end, and patient engagement begin? And, how are they intertwined? Find out here.
Home health coordination and management
Patients enrolled in digital clinical trials can access home delivery of all study supplies such as the investigational drug, relevant devices, and lab kits. If a trial requires blood pressure readings, blood draws, or other data collection that depends on professional assistance or expertise, home-health nursing visits can be arranged.
If biological specimens are required, home pickup can also be arranged. Home-health nurses can also be deployed for any drug administration that requires assistance or expertise.
Data collection and analysis
Through the use of wearables, apps, and other technologies, data collection can be frequent, continuous, time-stamped, and accurate. The primary benefit here is the data is captured for clinical interpretation in real-time, allowing the study team access to actionable data to make key decisions quicker than with traditional data collection.
Read more: Learn how to design patient-friendly and inclusive ePRO instruments that improve your trials.
Mobile devices and wearables
Consumers are becoming increasingly familiar with wearable devices, like fitness trackers and glucose monitors. In addition, 85 percent of Americans now own a smartphone. About three-quarters own a computer, and half own a tablet. These levels of connectivity have made remote data collection simpler and more convenient than ever before. With these mainstream devices (using either iOS or Android technology) and the rising familiarity in the use of wearables, patients and study teams can capture clinical outcome assessments electronically, either directly through a wearable sensor, or via the deployment of validated ePRO and eCOA instruments.
In addition to capturing key endpoint data and clinical outcome assessments, connected devices can also collect data on behavioral and physiological quality-of-life indicators such as sleep and vital signs. In some cases, connected devices can transmit data directly to patient portals.
Patient interactive portals
In the past several years, patient portals have become commonplace among medical providers. They empower patients to schedule and keep appointments, interact with their healthcare team, review their health records, and engage with content related to their health conditions. In a DCT setting, an interactive portal helps guide patients through each step of the clinical trial protocol.
- Patients can be reminded to take medication and keep appointments.
- They can also be reminded to record any daily data or symptoms the study requires – something that’s easy to forget when you’re not feeling well. If a patient experiences an adverse event, physicians can intervene in real time.
- Patients can see results from lab tests and view their own health data at any time, which helps them learn more about their own health trends, manage their treatment and stay committed to participating in the trial for its duration.
- Patients may also be able to interact with other participants via the portal, and stay informed about upcoming clinical trial participation opportunities.
Investigational product and study supply logistics
In this era of pandemic-related production and shipment delays, it’s critical to ensure that the supply chain for all study supplies is both robust and reliable. Smart and sustainable logistic solutions are integral to a direct-to-patient setting to ensure that investigational products, devices, wearables and lab kits arrive on time at patients’ homes. Project managers help study teams accurately predict country-specific needs and tailor distribution plans to ensure the right supplies are delivered safely to the right place at the right time, with minimal waste.
Benefits and value drivers of DCTs
Participants, Patients, & Caregivers
Virtual clinical trials are, by design, patient-centric. Patients no longer bear the burden of arranging transportation to and from a study site, or of taking valuable time away from work and family to participate. They don’t even need to live close to a study site. Instead, they can participate when it’s convenient for them with a trial that fits readily into their daily lives.
In fact, when trials are conducted remotely, they become more inclusive accessible to a much broader — and often, more representative — patient population, including those in rural and underserved communities. A 2018 study found that decentralized studies recruited three times as many patients as traditional models, and did so three times faster.
Patients like virtual trials better, too. In 2019, the Center for Information and Study on Clinical Research Participation (CISCRP) found that 75 percent of patients liked the idea of collecting all data in their own home; 73 percent found a hybrid trial design appealing. Beyond the convenience factor, patients can communicate more frequently and more easily with physicians and investigators during a remote study. This heightened connectivity includes a remote patient monitoring modality that provides comfort to patient and clinician alike. It also boosts patients’ engagement, satisfaction and compliance with data collection tools, including study diaries and questionnaires.
Read more: Learn about Improving Diversity in Clinical Trials, with an interview from an industry leader as she discusses progress in diversity.
Digitizing a clinical trial yields considerable benefits for sponsors. Recruitment becomes streamlined while also enabling faster enrollment of a broader and more representative patient population - thereby reducing the number of sites required to conduct the study. Once enrolled, patients in virtual studies have greater engagement and retention of key principles, as well as better adherence to the clinical trial protocol. That, in turn, leads to better retention of participants for the duration of the study.
Sponsors can specify whether data collection happens continuously or at specified times. In either case, with digital patient monitoring and unified workflows, data collection becomes standardized and more accurate. Real-time dashboards allow sponsors to track patient participation while TeleVisits enhance communication and patient safety.
All this results in cost savings for sponsors, while opening up new opportunities to build organizational intelligence around innovative clinical trial conduct.
Decentralized trials offer a more efficient, effective, and integrated delivery solution for even the most complex studies when sites are properly trained and supported.
From a site perspective, these solutions eliminate redundancies, improve the quality of data, enhance connectivity with the trial participants and, ultimately, result in better clinical care. They also allow sites to expand the number of studies they conduct, so they can work on advancing medicine and helping patients get access to effective treatments faster.
Contract research organizations that implement digital clinical trials can create competitive differentiation. By positioning themselves as experts in DCTs who can deliver better enrollment and retention, better quality data, and lower costs, they can drive more business to their brands. They can also position themselves as leaders in innovative clinical trial protocols.
Data considerations for DCTs
As a relatively new frontier, DCTs understandably raise questions about data capture and management and regulatory compliance. A number of organizations are working to ensure these and other best-practice issues surrounding DCTs are addressed. These include:
- Decentralized Trials & Research Alliance (DTRA)
Focused on accelerating the adoption of DCTs, this group has established four priority initiatives: defining key terms and performance benchmarks in DCTs; identifying and promoting best practices; building and sharing a knowledge repository, including an educational curriculum; and removing legal and regulatory barriers to DCTs.
- Digital Medicine Society (DiME)
This group of collaborative healthcare and technology professionals focuses on establishing evidence-based standards for research, as well as building community and disseminating knowledge in the digital medicine arena.
- Clinical Trials Transformation Initiative (CTTI)
CTTI offers an enormous cache of resources to the DCT community, ranging from trial design strategies and recommendations for mobile technology to guidance for working with IRBs.
This European-focused organization works to develop standards, recommendations, and tools for DCTs throughout the continent.
- American Telemedicine Association (ATA)
The ATA hosts frequent webinars, conferences, and other educational events and engages in advocacy, all in the name of advancing the efficient delivery of telehealth.
Because technology changes rapidly and DCTs are still relatively new, there is little standardization in data capture methodologies, though the Decentralized Trials & Research Alliance is working to prioritize that. Similarly, the Clinical Trials Transformation Initiative has developed a feasibility studies database that examines the technology used in hundreds of DCTs to date, in an effort to help sponsors and clinical operations teams select the best technology for specific endpoints. CTTI also has published a technology selection framework, which considers factors such as accuracy, resolution, sampling frequency, usability, data access and security, and more.
Regardless of what device you select — or even if your study operates in a BYOD (bring your own device) environment — one of the top considerations will be ensuring that every device is clinically validated and has all the regulatory approvals and certifications required in the countries where you’re operating them. At the very least, it should integrate seamlessly with a 21 CFR Part 11 or GDPR-compliant database to eliminate security risks. It should also be a recent enough model that you can expect manufacturer support for it to last at least for the duration of the trial. Other regulations can be found here.
The usability of data capture devices also will be critical to any study’s success. Patients should be able to easily enter or upload data without any external connections. Devices should not present obstacles to those with visual or dexterity impairments.
Allowing patients to see the data you capture during the trial on a dashboard — especially if it’s something that occurs daily, as blood pressure readings or a number of steps walked — can help patients feel even more engaged with the study.
Data storage and management
Before initiating a DCT study, sponsors and CROs will need to determine how collected data will be stored and managed. Ensuring data integrity as well as maintaining data security and patient privacy should be at the forefront of concerns. Teams will need to map out their anticipated data flow and select solutions that maintain security at each step. The CTTI recommends that teams collect the minimum amount of data possible to meet the study endpoints. The group further encourages use of systems that provide “secure, computer-generated, time-stamped, electronic audit trails of users’ actions and changes to data” during data transmission. Data security measures such as data encryption, tokenization and checksums should be implemented as well, the group says. It also recommends that teams regularly review and audit which users have rights and access to data.
Regulatory considerations for DCTs
In September 2018, CTTI published recommendations for conducting DCTs, with a focus on adhering to U.S. laws and regulations. Top among the group’s suggestions were:
- Ensuring that trial investigators are licensed to practice telemedicine in each state where they provide medical services as part of the trial.
- If investigational medical products are being shipped directly to patients, investigators must be aware of the applicable laws in the pertinent states.
- DCTs must meet all relevant data security and privacy regulations, such as HIPAA, GDPR and safety monitoring plans must be well documented.
- Study protocols must take pains to clarify the roles of various health care providers so that “routine care” and “clinical trial–related activities” are distinct and meet FDA regulations.
In 2020, the FDA published non-binding guidance in its document, “Conduct of Clinical Trials of Medical Products During the COVID-19 Public Health Emergency.”
To assure patient safety in the wake of the pandemic, the paper granted approval for “immediate” implementation of telephone and video-based visits, with documentation of any deviations from the original protocol, and subject to review by the IRB and notification to the FDA. The document further outlined key best practices, such as ensuring additional safety monitoring and obtaining informed consent.
In early 2023, the European Medicines Agency (EMA), European Commission (EC), and Heads of Medicines Agencies (HMA) acknowledged the growing role of decentralized elements in clinical trials and published a series of recommendations with a focus on data integrity, participant safety, and inclusion. The recommendation paper was published on December 13, 2022 but is not yet part of a harmonized approach with the national provisions of the individual EU member states, or with the United States. However, it is expected that the U.S. FDA will make similar recommendations later this year.
Read more: What does the new European Medicine Regulatory Network recommendation paper on decentralized elements in clinical trials tell us? Find out here!
Pillars to success
Perhaps the most important consideration in launching a successful digital clinical trial is to keep the focus on the patient. Consider the patients’ perspective in each decision so that every interaction they have, whether with study teams or technology, is positive.
Ensure that all the technology you’ve selected meets all benchmarks and requirements for validation and security before you begin. You’ll want to make sure sites are ready, too, before trials begin. Conduct feasibility studies to ensure staff are prepared for changes in the way they interact with and collect data from patients.
Now is the time for DCTs
While the COVID-19 pandemic may have been the spark that ignited more widespread adoption of decentralized clinical trials, we anticipate that the benefits of DCTs will endure long after the global health crisis ends.
According to the American Telemedicine Association, an astonishing 97 percent of U.S. physicians were using telemedicine in some form by April 2020; what’s more, 83 percent of patients expect to continue using telemedicine after the pandemic ends.
Clearly, patients and physicians alike have clearly become comfortable with remote healthcare.