Decentralized clinical trials: A patient-centric way forward
Throughout history, adversity often gave rise to innovation as we adapted to new challenges. Although the COVID-19 pandemic set back clinical trials – as 80% of non-COVID-19 trials were stopped or interrupted – it also spurred a revolution in how clinical trials are conducted. During the pandemic, prospective patients were unable or reluctant to visit physical research sites, while some sites paused ongoing trials as capabilities were shifted to critical care resources. The pandemic also further amplified socioeconomic disparities and made it more difficult to reach diverse patient populations, requiring stakeholders to further rethink and redesign the coordination of clinical trials.
With decentralized clinical trials (DCT) gradually on the rise in the last half decade, the adoption of this model has been slow. However, in what has been a historically risk adverse field, COVID-19 has now forced an accelerated risk mitigation response. And even though telemedicine and mobile healthcare providers have been used in healthcare services, the strategic concept of building a clinical trial around decentralization is still somewhat novel. This is partially due to regulatory uncertainty and a lack of clarity over what a DCT is and what it encompasses.
What is a decentralized clinical trial?
Historically, clinical trials focused on the top 3 KPIs: recruitment, retention, and protocol compliance. But in recent years, there has been a move towards a more patient-centric model. DCTs are the culmination of this trend – designing clinical trials based on patient needs, indication, and therapy. But as this model continues to evolve, there is a need to establish standard terminology. The term DCT already causes some confusion – is it a virtual trial, remote trial, hub-and-spoke-trial, site-less trial?
The definition of DCTs by the Association of Clinical Research Organizations (ACRO) keeps a patient-centric approach in mind:
“[DCTs] brings the trial to the patient by utilizing local healthcare providers, optimizing digital health technologies, and enabling the voice of the patient in order to accelerate medical product development, speed delivery of therapies to patients, and create efficiencies across clinical research processes.”
The FDA and EMA adopted the term decentralized clinical trial for any trial that does not follow traditional site-centered clinical trial models and incorporates digital methods, mobile technology, and local healthcare providers to communicate with patients and collect data. Although these definitions are quite broad, it highlights the advancement and inclusion of digital technologies in healthcare. DCTs should not be confused with virtual trials (although the name has been used interchangeably), which are preclinical trials conducted in silico or in models.
Specifically, DCTs may include:
- Remote eConsent: keeps enrollment timelines on track while keeping patients informed with electronic consent or re-consent
- Telemedicine: allows patients to stay connected with the study team and reduce the number of site visits
- Direct-to/from-patient delivery: sends supplies, samples, and unused investigational medications to and from the patient’s home
- Home health care and nursing: brings the clinical trial directly to the patient’s home
- Electronic Clinical Outcomes Assessments (eCOAs) and electronic Patient Reported Outcomes (ePROs): enables direct data collection and reduce paper and manual data entry with digital platforms
- Remote monitoring: allows the study team to maintain oversight of patient health
- Devices and wearables: uses sophisticated tools to gather more clinical data in a convenient, intuitive way for patients
DCTs exist on a spectrum from fully decentralized (completely site-less) to hybrid models that combine elements of both traditional and decentralized approaches based on the clinical trial, patient population, and available resources. DCTs are flexible; approaches can be tailored within a trial by including mixed patient enrollment, where some patients can still go to a traditional clinical trial site, while others can be enrolled and managed in a remote manner based on their needs.
During the COVID-19 pandemic, benefits of DCTs became even more apparent. Following new guidelines from the FDA and EMA, many sites adapted clinical trial protocols to ensure that patients could still safely receive care while social distancing. Some sites set up telehealth or remote patient monitoring to rescue ongoing trials or design new clinical trials. Seeing the need for a cohesive approach, the Decentralized Trails Research Alliance (DTRA) was launched in December 2020. The DTRA aims to form collaborations, create guidelines, and enable a harmonized framework for sponsors, CROs, and trial partners to follow, as well as to inform the industry on possible decentralized approaches.
Regardless of what term is used, the bottom line is that DCTs and hybrid trials have the potential to revolutionize clinical trials by making them much more accessible to patients while reducing burdens on physical sites.
Benefits of DCTs
DCTs take advantage of decentralized methods and digital technologies to address costs, patient enrollment, and diversity issues. These technologies can help make clinical trials more efficient by distributing information to patients more easily, increasing the speed of enrollment, and casting a wider net to a more diverse patient population. DCTs will help to reduce patient burden and increase clinical trial retention.
For patients the benefits are clear:
- Reduce time commitment with less disruption to work or school – allowing patients to maintain normal day-to-day activities
- Reduce barriers for patients with mobility constraints and physical or cognitive impairments
- Reduce transportation issues for patients without access to a car or public transportation
- Allow patients from underserved areas (e.g., rural, inner city) to access clinical trials
- Allow remote health monitoring for quicker contact with study teams
- Reduce patient burden by receiving direct-to-patient drug delivery and home visits
For sites and sponsors:
- Accelerate trial participation and reach more patients in a shorter time frame
- Improve patient retention due to fewer site visits, which reduces patients’ logistical and financial burdens (e.g., lost wages, childcare constraints, transportation costs)
- Evaluate more patients with less time-consuming remote assessments
- Reduce time spent manually entering data using digital and remote technology
- Evaluate patients in a real-world setting and in real-time (this is especially important for patients with certain indications that have acute flares that may be missed during site visits)
- Allow remote health monitoring for quicker responses to patient health
- Reduce site burden by using mobile healthcare services for home visits
Overall, DCTs empower patients to consider clinical trial treatment options by minimizing disruption to their daily lives. DCTs take the trial to the patient, instead of the patient to the site. DCTs also reduce site burden through mobile healthcare services and digital technology – making the drug development process more efficient and reducing overall costs. Lastly, DCTs can help to increase the diversity of recruited patients by removing physical distance barriers and may improve recruitment of patients with rare diseases.
Of course, as with any new process, there are several challenges and barriers that need to be addressed:
- For global clinical trials, sites need to follow each governments’ regulatory and licensing requirements
- Sponsors need clear guidance from regulatory bodies
- New technologies need to be validated and approved
- Mobile healthcare providers require oversight and responsibilities need to be consistent with local/national laws
- Supply chains require management, including all devices and investigational medicinal products sent to patient homes
- Training needs to be developed for sites and patients to ensure that the protocol is followed (new SOPs) and new technology is used correctly (intuitive and patient-friendly)
- Patient data privacy and data compatibility needs to be managed across platforms
- A human touch and patient needs should be maintained and considered (e.g., some may not feel comfortable with technology, prefer to see doctors in person, or are unsure of how to administer self-tests)
- Consider whether a country’s infrastructure supports DCTs (e.g., internet access, access to local hospitals with correct equipment/technology)
- Some procedures may still require site visits, or visits to local hospitals (e.g., radiology, infusions)
Still, the benefits outweigh potential barriers. As a growing number of clinical trials incorporate aspects of DCTs, regulatory agencies are now more willing to embrace decentralized solutions – particularly in the time of COVID-19. DCTs also push the industry to streamline electronic data systems so that data reporting and analyses are more efficient and have greater accuracy, while still maintaining data integrity. Setting up new methods, navigating new regulations, and validating new processes are all part of the natural process and growing pains of advancing clinical trials.
How does Clariness fit in?
Clariness uses a digital approach combined with patient understanding and site engagement that is congruent with a decentralized strategy. Clariness has already supported DCTs and hybrid clinical trials by using a patient-centric approach and working closely with sites to help them find well-qualified patients. Clariness also aims to tackle diversity issues in clinical trials by utilizing digital recruitment methods that target and attract eligible participants, while also taking into account patient population demographics.
A digital recruitment method also removes physical barriers to recruitment and helps to speed up the patient recruitment process, which reduces the overall costs of running a clinical trial. Over the last 15+ years, Clariness has followed a centralized patient recruitment model that has raised awareness and built a virtual community around clinical trials resulting in the patient portal, ClinLife®. ClinLife® helps clinical trials that are struggling to find enough patients and is active in over 50 countries with more than 10 million visitors per year. This centralized approach allows patients, study sites, and sponsors to all easily connect on one platform and has sped up the drug development process by 3 months or more.
A goal of a decentralized strategy is also to remove physical barriers by reducing dependency on site visits and thereby reducing patient and site burden. However, with less physical sites, patients still require regular engagement. Clariness’ Patient Enrollment Managers work closely with sites and support them with patient engagement and retention by regularly communicating with patients, providing materials for patients to read and stay informed, and being available to patients as needed. Sites are also provided with training aids and given assistance with scheduling visits or calls, or sending reminders to patients (e.g., taking medications).
During the COVID-19 pandemic, Clariness offered intensified support to reduce site burden and engage patients, which included customized trial support to manage patient retention and compliance through data collection and creating study-specific content; supporting individual sites directly; and engaging with study participants through multiple communication channels. Clariness also works with sponsors to amend protocols and SOPs. This support can be applied directly to future DCTs and hybrid models.
In addition to practical support, Clariness takes a patient-centric approach to clinical trials by performing patient insight surveys and highlighting the patient’s voice. Clariness conducts global patient surveys to understand what barriers patients face when joining a trial, what causes them to drop out, and to define acceptable risks or burdens. By incorporating the patient’s voice into the study design, this ensures a clear balance between the clinical study requirements and the patient’s reality grounded in patient insights.
As the COVID-19 pandemic has forced a faster change in pace, the response in the industry has been overwhelming. These adaptations show that clinical trials can quickly evolve and be conducted in a decentralized way that still keeps patient needs at the center.
If you are interested in how Clariness can support your decentralized or hybrid clinical trial, please don’t hesitate to contact us
The CLARINESS Team is here to help YOU overcome challenges in conducting clinical trials as we adapt during these extraordinary times.
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