In the ever-evolving landscape of clinical research, the traditional brick-and-mortar model of clinical trials is being transformed by the advent of decentralized clinical trials (DCTs). At its core, a DCT leverages technology and remote monitoring techniques to conduct clinical research, reducing or possibly eliminating the need for participants to be physically present at a centralized location. This model isn't just a fleeting trend, but rather a response to the pressing challenges faced by conventional trials, particularly in patient recruitment, accessibility, diversity, and cost efficiency. For example, study participants often must make frequent visits to study sites. Such regular visits can deter potential candidates, especially those from underserved or remote areas, from participating in a clinical trial. By decentralizing these trials, we not only open doors for a wider, more diverse participant pool but also reimagine a more patient-centric approach to clinical research.

On this page we want to explore in depth the concept of a DCT; not simply as an alternative method of conducting a trial, but as an element or component that can help improve patient recruitment, patient retention, and patient-centricity. Conversely, we will identify some of the challenges related to DCTs. Finally, this page will offer some best practices and considerations when designing a DCT or implementing some DCT-related technology or practice.

Table Of Contents

1. Benefits Of Decentralized Clinical Trials
2. Maintaining Ongoing Engagement And Adherence
3. Regulatory and Ethical Implications of DCTs
4. Ensuring Data Integrity & Security
5. Quality Assurance and Oversight in DCTs
6. Disadvantages Of Decentralized Trials
7. Examples Of Decentralized Clinical Trials
8. The Future of Decentralized Trials

 

Benefits Of Decentralized Clinical Trials

The expected advantages of DCTs are manifold, weaving together benefits for both researchers and participants alike.

• Enhancing Patient Accessibility and Convenience: One of the biggest advantages of DCTs is their ability to significantly mitigate geographical barriers, making it easier for participants to enroll and partake in trials. This not only increases the diversity of the participant pool, but it can also increase the amount of participants enrolled by providing access to those who live in remote areas where traveling regularly to a traditional site would be cumbersome or costly.

• Cost Efficiency: Traditional clinical trials are often accompanied by high overhead costs, encompassing site expenses, on-ground staff, and travel stipends. DCTs, through their virtual nature, can — depending upon the technology chosen and the training needed for it — reduce these expenses. A thorough cost-benefit analysis should guide the decision-making process when opting for a DCT.

• Rapid Recruitment and Retention: Part of the intent of DCTs is to accelerate the recruitment process through access to a larger and more diverse participant base. Similarly, the convenience of DCTs could lead to lower participant dropout rates as compared to conventional trials.

• Real-time Data Collection: Leveraging digital health tools, DCTs can facilitate continuous, real-time data collection. Wearables and remote-monitoring tools provide a constant influx of patient data, allowing for timely interventions, enhanced safety monitoring, and data-driven insights.

 

Examples of digital assessments, endpoints, and biomarkers for clinical trials (Image credit: Sanofi)

 

Maintaining Ongoing Engagement And Adherence

With the absence of regular in-person check-ins, maintaining participant engagement with a DCT can be challenging. Although digital platforms can be used in traditional trials to deliver information such as a study’s objectives, procedures, and safeguards; patient rights; and trial outcomes, technology plays a much larger role in DCTs. Social media campaigns, virtual webinars, interactive apps, and email newsletters are effective tools to maintain ongoing communication, share study updates, and address patient queries. Gamified elements, milestone rewards, and regular feedback loops can encourage continuous participation. SMS reminders, interactive challenges, and virtual peer communities can further enhance adherence to study protocols.

But digital doesn't mean impersonal. Virtual helpdesks, teleconsultations, and chatbots can offer real-time assistance, ensuring participants have a support system whenever they encounter challenges.

Technologies Commonly Used In Decentralized Trials

The following are some of the fundamental technologies that form the backbone of DCTs.

1. Mobile Health Devices and Wearable Technology: Modern DCTs heavily rely on wearables and mobile health devices to collect patient data remotely. From smartwatches that monitor heart rate and sleep patterns to specialized devices that track specific health metrics, these gadgets enable continuous data collection without participant discomfort.

2. Telemedicine Platforms: Essential for remote patient consultations, telemedicine platforms facilitate virtual interactions between researchers and participants. This digital bridge not only keeps the communication channels open but also allows for timely interventions, ensuring patient safety and study adherence.

3. Digital Patient-Engagement Tools: Digital engagement tools, like mobile apps and interactive platforms, send reminders, share educational content, and provide a medium for participants to report symptoms or ask questions, fostering a sense of involvement and trust.

4. Data Storage and Security Protocols: With the massive amounts of digital data generated, DCTs necessitate robust storage solutions. Cloud storage, integrated with strong encryption and cybersecurity measures, ensures data integrity and confidentiality, addressing potential concerns related to data breaches or misuse.

5. eConsent Solutions: The digital realm of DCTs requires a reimagined approach to informed consent. eConsent platforms facilitate the remote delivery, comprehension, and acknowledgment of study information. These platforms, often interactive, prioritize clarity and ensure participants are fully aware of study implications.

Other Components Of DCTs

According to ISR Reports’ 2022 “Decentralized Clinical Trials Outlook,” some other common decentralized components include:

• Direct-to-patient shipment of investigational medicinal product (IMP)
• Home nurse visits
• Local/Community Labs

 

 

Regulatory and Ethical Implications of DCTs

As DCTs gain traction, regulatory bodies worldwide are adapting their guidelines to encompass this new model. For instance, the U.S. FDA has been proactive in providing guidance for DCTs, focusing on data quality, patient safety, and the use of electronic solutions. Some other useful links regarding DCTs worldwide include:

• FDA Guidance On DCTs Webinar
• EU Recommendations for DCTs
• UK Guidance on DCTs
• Canada’s discussion on DCTs

In conjunction with regulatory changes, the increased prevalence of DCTs has prompted some ethical concerns. For example, eConsent, which is especially useful for a DCT, must still uphold the principles of traditional informed consent. Thus, an eConsent platform should not only ensure participant comprehension (e.g., via interactive modules, videos, and quizzes), it must provide an easy way for patients to contact study personnel for clarifications.

Another ethical consideration is that DCTs may unintentionally exclude those without access to technology or digital literacy. In those instances, efforts must be made to provide necessary resources (e.g., Wi-Fi) or alternative-participation methods, such as providing home nurses to record participant data.

 

Ensuring Data Integrity & Security

Similar to regulatory and ethical concerns, the potential for broader data collection, such as continuous monitoring, raises questions about patient privacy and data security related to DCTs. That’s why it’s imperative to develop robust encryption, secure data storage solutions, and clear data-handling policies. Of course, study participants always should be informed (via the informed consent document) about who will have access to their data and for what purposes. Some issues to consider on this topic include:

• Data-Collection Tools: In DCTs, data collection extends beyond the traditional patient-reported outcomes. Wearable devices, mobile apps, and remote monitoring tools can provide a continuous stream of patient data. Ensuring the reliability and accuracy of these tools is paramount to maintaining data quality.

• Data Integration and Harmonization: With multiple sources of data influx, integrating them into a cohesive dataset is a significant challenge. Platforms should be capable of harmonizing different data types, formats, and sources to create a singular, coherent database.

• Ensuring Data Integrity: The remote nature of DCTs brings forth concerns about data tampering or misrepresentation. Implementing real-time data validation and verification protocols, backed by blockchain or similar technologies, can enhance trust in the collected data.

• Data Storage and Backup: Cloud storage solutions, equipped with robust encryption, offer scalable and secure storage options for DCTs. Regular backups and redundancy plans are essential to prevent data loss.

• Data Access and Sharing Protocols: Clearly defined policies should be in place regarding who can access the data, under what circumstances, and for what purpose. Ensuring patient confidentiality while facilitating data sharing for research purposes requires a balanced approach.

• Analytics and Insights Extraction: The vast amount of data generated in DCTs holds untapped potential for insights. Advanced analytical tools, powered by AI and machine learning, can sift through the data, identifying patterns, predicting patient outcomes, and offering actionable insights for researchers.

 

Quality Assurance and Oversight in DCTs

 QA and oversight are fundamental to the success of any clinical trial, but in the context of DCTs, they assume even greater significance due to the inherent challenges of the model.

Also, given that DCTs largely rely on digital platforms, wearable devices, and remote interactions, a multifaceted QA system is crucial. This system should be agile, capable of evolving in tandem with technological advancements, and patient-centered to ensure all touchpoints are governed by quality standards. For example, any remote monitoring tools used with a DCT should be able to verify data integrity in real-time, detect anomalies, and alert researchers to potential discrepancies or concerns.

• Standard Operating Procedures for DCTs: While the core principles of clinical research remain unchanged, DCTs necessitate SOPs tailored to their unique requirements. These SOPs should address areas such as informed consent, remote adverse event reporting, and data security measures.

• Training and Certification: Ensuring that all personnel involved in the DCT are well-versed with its nuances is crucial. Regular training sessions, certifications, and refresher courses can ensure that the trial is conducted to the highest standards, regardless of the decentralized model.

• Data Audits: Regular and random audits of the collected data can reinforce its integrity. Automated audit trails, coupled with manual reviews, can provide a holistic view of the trial's quality parameters.

• Risk Management and Contingency Planning: Proactively identifying potential risks — be it technological glitches, patient non-compliance, or data breaches — and having contingency plans in place can ensure swift resolution while maintaining the trial's integrity. Risk management also includes alerting researchers to potential safety issues; for example, if a wearable device records a sudden drop in a participant's heart rate, the information should be immediately sent to the PI and flagged as "high priority." Although this adds an extra layer of contingency planning to DCT design, real-time participant data can improve safety.

• Stakeholder Collaboration for Oversight: Regular reviews and consultations with stakeholders, including patients, can offer a comprehensive perspective on the trial's quality. Transparent communication and a commitment to continuous improvement can further bolster QA.

• Regulatory Adherence: Aligning with regulatory guidelines is not just a compliance requisite but also a cornerstone of quality. Regular updates, documentation, and ensuring that the DCTs adhere to both local and international regulations is paramount.

 

Disadvantages Of Decentralized Trials

There are hurdles and constraints that researchers likely will encounter when designing and or implementing a DCT framework. First and foremost, without as much physical oversight as traditional clinical trials, ensuring that participants adhere to trial protocols or take medications as prescribed can be more complex. So, too, is maintaining clear, consistent, and immediate communication with participants to avoid potential misunderstandings or reduced patient engagement.

Clinical trial sites also may incur challenges from DCTs. Additional technology for a protocol can be a burden on already time-strapped site personnel. Further, data being collected from non-site-related HCPs can complicate coordination of a trial for sites.

While the remote nature of a DCT has its advantages, the reduction in face-to-face interaction can make some participants feel detached or less engaged, which can influence their experience and, in some cases, their commitment to the trial. A similar double-edged sword conundrum exists because of the globalization opportunities presented by DCTs; a more diverse pool of patients introduces complexities like cultural differences related to patient engagement as well as linguistic barriers related to trial comprehension. As DCTs progress, there might be unforeseen infrastructure requirements, in terms of advanced analytics, cloud storage solutions, or patient support systems.

It is important to remember that not all studies may be suited for this approach. Trials requiring intensive medical procedures, frequent physical assessments, or specialized equipment might be more efficiently managed in traditional settings. Furthermore, don’t let the allure of promised cost savings overshadow what should be your true catalyst for adopting a DCT — improved patient-centricity, however you define it.

 

Examples Of Decentralized Clinical Trials

To truly grasp the potential and efficacy of DCTs, it's invaluable to examine real-world examples. Currently, many trials are using DCT elements, and below are notable examples of completed and ongoing trials who successfully navigated the challenges, demonstrating the tangible benefits of this innovative research approach.

Pfizer’s REMOTE Trial

• Background: In 2011, Pfizer launched the first-ever fully remote clinical trial, the REMOTE (Research on Electronic Monitoring of Overactive bladder Treatment Experience) trial, aimed at studying overactive bladder condition. While the trial faced challenges like recruitment difficulties and was eventually terminated, it paved the way for further exploration and understanding of decentralized methodologies.
• Approach: Patients used mobile apps and online platforms for everything from recruitment to data collection. They also received investigational drugs by mail.

Advicenne ARENA2 Trial

• Background: Began recruiting for the rare kidney disease trial in 2019 but was put on hold when COVID-19 hit. The original design required patients to go through a six-day withdrawal period after receiving the active drug or placebo in a hospital setting.
• Approach: Blood draws previously conducted in clinics were performed by nurses in patients’ homes. Patients could record outcomes they experienced and schedule appointments using an app/platform and there would be telemedicine calls with the doctor.

Janssen CHIEF-HF Trial

• Background: Included 448 randomized patients recruited between March 2020 and February 2021. CHIEF-HF stands for Canagliflozin: Impact on Health Status, Quality of Life and Functional Status in Heart Failure. The study demonstrated that canagliflozin resulted in a rapid and clinically meaningful improvement in the symptoms of patients with HF.
• Approach: Designed to have no in-person site visits, participants were given their study medication and a Fitbit and completed an eDiary of medication use. Ninety-five percent of participants completed their eDiary and 91% took more than 80% of their medication.

Johns Hopkins University REACT-AF

• Background: Rhythm Evaluation for AntiCoagulaTion with Continuous Monitoring of Atrial Fibrillation (REACT-AF) launched in July 2023 and is expected to run through July 2029. This large, pragmatic study of over 5,000 participants is testing an alternative anticoagulation therapy for patients with atrial fibrillation (AF).
• Approach: This hybrid trial incorporates decentralized elements, which is expected to improve data collection while decreasing trial costs by 50%. After enrollment, no in-person follow up visits are required, and participants use an Apple Watch to collect data remotely.

The National Patient-Centered Clinical Research Network (PCORnet) PREVENTABLE

• Background: PRagmatic EValuation of EvENTs And Benefits of Lipid-Lowering in OldEr Adults (PREVENTABLE) is a hybrid trial utilizing pragmatic data sources for a target sample size of 20,000 participants.
• Approach: The trial uses randomized evidence to determine whether statins reduce cognitive and functional decline in older adults. Recruitment completed in April 2023, and the trial will conclude in 2026. As a hybrid trial, participants are required to visit sites for period blood draws and performance tests, but visits are supplemented with a call center that performs annual assessments.

 

The Future of Decentralized Trials

As the benefits of DCTs become more evident, an increasing number of pharmaceutical companies, biotechs, and research institutions are likely to adopt decentralized methodologies. This shift will be further fueled by patient demand for more convenient trial participation. Additionally, a balanced (i.e., hybrid) approach might emerge where trials incorporate both decentralized and traditional elements, offering flexibility to participants and researchers alike.

Wearable devices, Internet of Things (IoT), and AI will play pivotal roles. Enhanced remote monitoring capabilities and real-time data analytics will ensure DCTs are not just feasible but also more efficient than traditional trials.

As DCTs gain momentum, regulatory bodies worldwide will refine and expand guidelines tailored to decentralized methodologies. This will ensure that DCTs maintain rigorous standards of safety and efficacy while leveraging the advantages of remote participation.

In essence, DCTs represent a paradigm shift in clinical research. By prioritizing patient convenience, embracing technology, and optimizing costs, they herald a more inclusive, efficient, and data-rich future for clinical trials, underlining the potential to revolutionize the way medical research is conducted.

 

Additional Resource:

The Decentralized Trials Research Alliance (DTRA) resource library provides a comprehensive collection of DTRA content supporting the adoption of DCTs.