The only mandatory obligation for sponsors was to accurately flag datasets that were generated with remote engagements and those with in-person subject interactions (FDA, 2021, April 12).

Overview of Decentralization Clinical Trials

Today, the concept of DCTs is used almost synonymously with words such as virtual, home, remote, distributed, and home-based or site-less trials. In general, a decentralized trial can be characterized as a hybrid model that uses a combination of traditional and virtual trial elements rather than a specific type of approach. It is important to note the goal of DCTs is to simplify the patient-physician engagement but this does not mean that all clinical trial interactions are limited to a virtual setting. The hybrid approach encourages personal meetings depending on the context of different clinical trial events.

In all the variations of DCTs, “patient-centricity” has remained the primary area of focus for sponsors and CROs. As participants will have ease in participating remotely, a higher retention rate can be expected during the course of the clinical trial. Therefore, DCTs can be considered as a potential patient-focused approach to clinical trial design. Here’s how they are faring currently and what is expected of them as they evolve.

How Modern Technology facilitates the conduct of DCTs

Today, technology innovation has made virtual interactions seamless with a close-knit digital connectivity with real-time video conferencing using powerful smartphone apps. The explosion of intelligent health monitoring wearables and sensors and interconnected electronic medical records systems have considerably transformed data collection and sharing. DCTs use these “virtual tools” to grow in parallel with “virtual medicine,” accelerating clinical trial design.

In a fully decentralized clinical trial, patient recruitment, delivery of study medication, and procurement of trial outcomes data all proceed without involving in-person contact between the investigators and the patient. Currently, clinical trials for drug approval already include decentralized elements and their contribution continues to grow.

Current state of DCT adoption

A recent study found 76 percent of investigators are now performing decentralized trials due to the pandemic, with 38 percent representing more than half are decentralized. Thus, it is imperative to employ this approach to ensure patient safety, retention and effective trial participation during the pandemic.

Telemedicine applications, wearable devices and other technological support systems have been contributing to the move to DCTs even before the current crisis. FDA approved devices have been in real-time adoption to monitor patients with rare diseases and special needs. However, it is clear that the pandemic has been a key driver for DCT adoption. In its current state, the contribution of individual technologies for DCTs has been identified as follows:

• Mobile technologies with the greatest means for patient access have been used in 77% of the DCTs
• Wearable devices have been used in 60% of the cases
• In-home devices are actively being used in 54% of decentralized studies
• Sensors and AI/ML have been used in 35% and 31% cases respectively
• Other uncategorized technologies were also found in 9% of studies

Establishing the site-sponsor connection for DCTs through software integrations

A decentralized approach replaces several site visits for patients with a healthcare provider (HCP) making a home visit, or with an online mobile application that facilitates data collection without needing patients to attend the site. This is made possible through software integration and virtual collaboration between the researcher sites and local medical teams, enabled by digital technologies. This connection allows research sites to receive accurate patient data from local physicians’ offices, pharmacies which can then be shared with their sponsors. According to a recent study by WCG, 97% of the research sites are anticipated to use at least one remote monitoring tool to connect with their sponsor. The software integration for site-sponsor connection will impart the following benefits:

• Real-time monitoring: Real-time monitoring allows sponsors to monitor site’s progress without having to visit the site in person each time.
• Instant document and data exchange: Sites can upload their regulatory documents, lab results and other essential documentation to a secure online database. This allows sponsors to view documents without waiting on emails or faxes and can electronically share eTMF documents with sites as needed.
• Automated workflows: Integrated software systems link the programs and automatically transfer data without having the clinical research staff spend long hours transferring data from electronic health records (EHRs) to electronic investigator site files (eISF).
• Remote Source Data Verification (SDV): Sites can instantly share up-to-date source data with sponsors for verification.
• Site Network Expansion: Sponsors can expand their site network by working with sites located in different states or even countries by transferring essential documentation through a single secure online system.

Legal, Regulatory and Practical Considerations that Affect the Adoption of DCTs

Although the concept of DCTs has been widely discussed in the last three years, the primary constraint in implementing it as a practice is the lack of regulations. Decentralization, like most new innovations, adds a different type of complexity to implement it as part of the core clinical trial process. Sponsors must study how effectively they can implement DCTs, and support patients and sites. With the remote nature of DCTs, obtaining eConsent, delivering direct-to-patient drug shipment, facilitating in-home healthcare visits, managing data collection via devices and wearables, plus video-based physician consults are key areas that need new thinking from sponsors.

Deciding on the best decentralized strategy to most effectively execute a given protocol depends on how it impacts patient experience. It requires stakeholders to dedicate time to managing and processing a high volume of patient data received through online applications and wearable devices. Inconsistency of visiting HCPs could potentially be distressing for elderly and to those participating in trials related to serious diseases. Patient attitude also contributes to the difficulties as some patients may be more comfortable being seen in person. This may especially be the case for the elderly, or those participating in a trial for the first time.

Any kind of technical failure can result in a loss of patient data which in turn could be a critical endpoint for the clinical study. Resolving technical issues can delay the trial progression and result in data inconsistencies. While it’s important to be aware of these challenges, the benefits of decentralized trials could outweigh potential risks which with the right approach can be appropriately mitigated.

Deriving Value Through DCTs

Decentralization focuses mainly on making clinical trial participation an easy process, enabling participants to continue with their day-to-day lives with minimal disturbance. Studies have revealed that nearly 70% of patients live more than two hours from a research site. In 50% of clinical trials, participants find it hard to remain enrolled due to poor health and 85% of trials fail to retain enough patients.

Decentralization can help mitigate these hurdles by speeding up recruitment, enhancing compliance and curtailing drop-out rates. They have the potential to positively impact clinical trial development in numerous ways by:

• Expediting patient recruitment by making it easier to find and recruit potential subjects especially from rural areas where travel to/from sites is difficult.
• Increasing diversity by facilitating patient recruitment from a much wider area rather than limited to those within a distance of a participating site. This benefits rare disease research.
• Patients become more informed and engaged as a result of autonomy enabled by technology. Electronic records can be automatically time-stamped and verified as and when required.
• Improve reliability and accuracy of data by collecting data using technology such as wearables, apps, and smartphones can keep data more organized and safe.
• Streamline experience: DCTs reduce the burden of time consumed during in-person visits and enable wider patient access.
• Gather reliable real-world data: Collecting high-quality clinical and real-world data through DCTs can build stronger evidence and reflect the value created for patients.
• Digital solutions enable a unified user experience and one source of truth for data integration.

Conclusion

Traditional clinical trials may not be viable for the pharmaceutical industry in the future which faces tremendous pressure to deliver more than ever. As the healthcare industry anticipates seeing an increase of new infectious disease outbreaks in the near future, innovative approaches such as the introduction of DCTs could pave the way to extend the continuum for new medical research and clinical development in which case decentralization should be considered both at an enterprise level and tailored to the specific protocol.

The crux of the problem lies in finding suitable approaches that can deliver on the promise of ‘patient-centric’ care that focuses on reducing patient burden and engaging with them better for achieving positive outcomes. Irrespective of any new phenomenon, sponsors, CROs and Sites will have to identify opportunities to adopt, adapt and transform in a regulatory compliant manner with an unwavering focus on patient safety. To conclude, it’s apt to say that remote clinical trials are gradually becoming a possibility and it truly has the potential in shaping patient-centric engagement throughout the clinical development journey.