Clinical Researcher—May 2021 (Volume 35, Issue 4)

SPECIAL FEATURE

Alison Holland

 

Decentralized clinical trials (DCTs) have existed for nearly two decades. However, DCTs, which incorporate advanced digital and remote technologies to conduct much of a trial at a patient’s home, accelerated dramatically due to the COVID-19 pandemic. Global healthcare advancements could not afford to be stagnant, so sponsors and their partners shifted to this new model suddenly. The result was a 400% growth in DCTs that’s expected to continue as more industry leaders recognize the economic, speed, and diversity benefits of this new model. In fact, 73% of sponsors and contract research organizations (CROs) say that they are currently using a hybrid decentralized model or plan to in the next two years.{1}

The randomized clinical trial model has needed an overhaul for decades, in part because of the lack of access to patients. Finding good candidates in the right locations, especially for rare disease trials, is difficult and contributes to 85% of trials failing to get enough patients enrolled. For patients who do enroll in a trial initially, an eye-popping half find it difficult to stay enrolled.{2}

Traditional trials have well-documented hurdles to patient enrollment and retention. Typically, 70% of participants live more than two hours from a trial site and face financially burdensome barriers, including transportation, missed work, or lack of childcare making it nearly impossible to make site visits, sometimes multiple times a week.{3} These barriers exclude many low-income participants.

These long-standing challenges, coupled with the unique benefits of decentralized approaches, ensure the trend toward DCTs will continue well past the pandemic. Even so, perceived implementation barriers are causing some CROs, sponsors, and principal investigators (PIs) to remain cautious—potentially losing out on the leaps in efficiency, data quality, and patient enrollment and retention that DCTs afford. Here, we address the five most common obstacles, and how to overcome them.

Change Management

The life sciences industry has always been hesitant to change. With health at stake, everyone involved in a trial wants to be confident about how it is conducted. From CROs to PIs, the whole team must be on board to make a DCT successful. Education is key. Make sure everyone on the team is fully aware how decentralized aspects of the trial will help each team member do his or her job better, such as using eConsent tools to reduce or eliminate repetitive or manual data entry tasks. Digital tools in DCTs allow site clinicians to spend more time focused on the patient rather than paperwork.

Constant communication about expectations around process change and collaboration is also critical. Everyone involved in the trial process should expect to invest extra time up front to establish new ways of working together with the knowledge that it will save time in the long run. Disarm site teams about the misperception that DCTs will eliminate some long-standing research roles by clearly explaining how these roles will evolve, not go away. For example, with fewer manual workflows, researchers will be more efficient and can focus on more value-added activities and patient care.

“DCTs are not a one-size-fits-all solution, and every project should be assessed independently in the context of need, value, and return. This requires an experienced team,” said Mike D’Ambrosio, vice president of real-world evidence and late-stage trials at Syneos Health.

For instance, D’Ambrosio noted that digital tools, artificial intelligence (AI), and machine learning platforms have been leveraged in support of COVID-19 vaccination trials to organize, analyze, and clean thousands of datapoints in less than 24 hours versus months if done manually. Sponsors and clinicians can leverage these decentralized tools to both improve data quality and optimize resource time, allowing them to work smarter and more efficiently, he added.

Technology Adoption

The perception that certain patients will not use or understand new technology is largely a myth. Researchers are finding that patients—including older generations—are more familiar with technology than credited, and eager to comply. The key is to decide what technology to use and then provide the right support and education.

In a recent decentralized study on macular degeneration—a disease that primarily impacts people over age 65—researchers found that age had no bearing on the use of remote technologies. The study, which needed to happen quickly and cost-effectively after being delayed for years, used digital technologies to screen 11,000 patients remotely for a rare genetic variant.

This trial would typically require more than 100 physical sites with patients living within a set radius of each and was forecast to cost upwards of $50 million. So, the sponsor took a decentralized approach to eliminate the need for physical sites. A single DCT platform was used to recruit, on-board, and oversee participants, slashing patients’ time burdens in half. Patient enrollment, expected to take upwards of six months, took less than three weeks and the trial cost $20 million less than forecasted. Patient retention was near 100%, too, suggesting that remote technologies did not intimidate an older population.

Seniors have dramatically increased their technology use during the pandemic, using virtual tools for everything from booking virtual visits with their doctors to ordering their prescriptions online. Six in 10 seniors recently surveyed said they are embracing technology more than ever. In fact, telemedicine usage jumped 340% among Medicare-eligible seniors since the start of the pandemic.{4}

Digital Immaturity

The first fully virtual clinical trial was Pfizer’s groundbreaking DCT of 2011, which leveraged mobile phones to capture patient data and keep patients remotely in touch with sites across 10 states.{5} The U.S. Food and Drug Administration (FDA) hadn’t quite caught up to advancing technology and solutions providers were still in the nascent stages of development.{6} Consequently, early DCTs lacked, tainting the model as a viable option long-term. Early negative experiences and the perception that technology still isn’t ready have prevented some from investing in DCTs.

However, cloud innovations, the Internet of things,{7} and advanced mobile technologies provide a modern, reliable pathway for DCT implementation even as the industry is still evolving.

“Some people worry we are evolving too quickly—saying that we haven’t figured out DCT version 1.0 yet and we are already at version 5.3,” noted D’Ambrosio. “I don’t think this is the case, but rather it demonstrates the critical requirement for robust change management. Technology is going to continue to evolve at light speed and with broadening utility. Rest assured, we will always adhere to strict compliance standards and test before roll-out. Each DCT project, site, patient, and protocol is unique. That is our challenge now—thoughtfully selecting and applying world-class solutions to meet all of the wider needs of the project stakeholders—not the technology per se.”

To reduce potential technology issues, in some instances, it may be appropriate to have trial participants use their own device. Most importantly, DCTs should leverage a single platform with built-in flexibility to accommodate unique needs and changing requirements, sometimes mid-trial.

For example, in a recent hemophilia study, patients were recruited and onboarded through one DCT platform. They scheduled blood tests directly through the platform app. Once their blood was taken, the results went back through the same platform. Using a common platform allowed PIs and doctors to easily collaborate and see the same data in real time, eliminating the silos with traditional trials.

Data Consistency

With patients dispersed and a mix of access to different technologies, another barrier is the potential for data inconsistencies. It’s vital for teams to get consistent and comparable data, no matter where the patient is based. To do this, the same approach must be used with each participant, including when using a physical device to gather data. For instance, if patients are in China, Norway, and Ethiopia and will be given a consumer-grade wearable device to capture data, then each participant must be provided with the same device. Patients must also be taught how to use the device, to ensure the same data are collected from each participant in the same way.

“What is the purpose of the data collection? Is it exploratory data or data that will support an endpoint and must be regulatory grade? The key is to delineate between the two to determine the level of tolerance for variation on data collected from patients,” explained D’Ambrosio. “With an [electronic patient-reported outcomes]–based clinical endpoint, for instance, standardization is critical because the data collected are directly tied to primary outcomes so there is much less tolerance for variation. Any DCT solution will need to leverage a robust, qualified system with a standardized way to capture data as well as a formal training program that teaches patients how to use that technology so patients can interpret questions in the same way.”

It’s critical to maintain a single data collection point and to provide patient participants with everything they need to use the technology correctly. DCTs must have a dedicated team with set processes to consult and make changes to data collection processes, when necessary, to ensure data consistency.

Additionally, DCTs should leverage the lowest common denominator technology for patients and be flexible about how data are collected. For example, in one DCT taking place across 43 countries, participants need to be informed in their language so they can properly consent to their data being used. However, all patients must consent using the same guidelines in the same way for compliance. Technology allows the process to be standardized yet also accommodate each person, no matter their location or language.

Compliance with Global Regulations

Global DCTs demand a laser-like focus on local regulation compliance. For instance, eConsent processes may be governed differently in different geographic areas. However, global traditional trials also require compliance across continents. Recognizing the need for quicker adoption, the U.S. and European Union eased some restrictions to make DCTs easier to execute. In December 2020, the Decentralized Trials and Research Alliance (DTRA) was formed to advocate for more DCTs. Further, the FDA launched the Digital Health Center of Excellence in the fall of 2020, in part, to advance digital health technology used in DCTs.

The key to success in this area is to have a set person or team overseeing rules and regulations where each trial participant is based. The team must be proactive in its pursuit of global compliance. “There are concerns around scaled adoption of certain elements of a DCT such as eConsent due to ambiguity with different regulators in certain geographies. But there are data and learnings around adoption, retention, and other parameters that we can start to gather and then share the successes around eConsent in a vendor-agnostic way,” said Dr. Craig Lipset, co-chair of DTRA.

With trials happening anywhere, DCT teams need to make data maps to understand before a trial starts how data will be used, where they will be gathered, and where they will ultimately go. Data mapping is vital to staying in compliance with data regulations, and it takes a team to stay on top of a data map. The trial sponsors must also be ready to modify the data map or change course as needed. Given the advancements of 2020 and clarified regulatory direction from the FDA and European Medicines Agency, complying with global data regulations is projected to get smoother as time goes on.

The Next Phase of DCT Adoption

For some organizations, DCTs still feel “all arms and legs,” like teenagers experiencing a growth spurt. As more organizations become familiar with this model and recognize its positive impact, the industry will grow seamlessly into its new DCT physique.

Few things worthwhile are risk-free. DCTs allow patients anywhere in the world to participate in life-altering clinical trials by removing many access barriers for diverse participant pools. DCTs will transform healthcare but won’t evolve without some growing pains. The key is to minimize risk where possible and maximize potential outcomes, working with experts to mitigate all perceived barriers to implementation.

“DCTs are fast-evolving and every day there is a new puzzle to unravel. There is a level of immaturity still and some unknowns, but the benefits far outweigh the extra effort to solve these complex problems,” concluded D’Ambrosio.

References

1. McAvoy R. 2021. ISR Reports. Warming Up to Hybrid Trials. Clinical Leader. Full resource here.
2. Advarra Report. 2021. Retention in Clinical Trials: Keeping Patients on Protocols. Full resource here.
3. The National Academies of Sciences, Engineering & Medicine. 2019. Virtual Clinical Trials: A New Model for Patient Engagement. Full resource here.
4. Health Insurance.com. 2020. Medicare-Eligible Seniors Survey Findings: Technology, COVID-19, the 2020 Election, and More. Full resource here.
5. Pfizer Conducts First ‘Virtual’ Clinical Trial Allowing Patients to Participate Regardless of Geography. 2011. Press release here.
6. Donahue M, Henderson L. 2012. Pfizer’s REMOTE Virtual Experience. Applied Clinical Trials. Full resource here.
7. https://en.wikipedia.org/wiki/Internet_of_things

Alison Holland (alison.holland@medable.com) is head of virtual trials at Medable with more than 30 years of experience conducting clinical trials. Previously, she was global vice president and general manager for general medicine at Covance. She has managed more than 300 clinical trials, working successfully with biotech organizations and global pharmaceutical firms on some of their most critical initiatives.