Clinical Researcher—December 2020 (Volume 34, Issue 10)

TRIALS & TECHNOLOGY

Alison Holland; Jena Daniels; Rasmus Hogreffe; Ingrid Oakley-Girvan, PhD, MPH; Dr. Michelle Longmire

 

If 2019 was the year of personalized medicine, 2020 was the year of decentralized trials. Ready or not, the COVID-19 pandemic ushered in a new era of clinical research—the advantages of which are only just beginning to blossom. Beginning this year, the life sciences industry will see new virtual trial designs adopted by a much larger, broader section of sponsors, sites, and patients. As a result, expect great strides forward in trial access and participation, the growth of real-world evidence to enable better outcomes, and huge leaps in trial efficiency and speed.

In this column, Medable experts share their predictions on changes that will shape the clinical environment in 2021.

The Flexibility of Decentralized Trials Will Drive Widespread Adoption

Alison Holland, Head of Decentralized Trials

The promised decentralized trial (DCT) revolution has gained traction in 2020, but we have significant progress yet to achieve, even as we see bolder commitments to this more patient-centric, more efficient model today. Industrywide, the decentralized approach to clinical trials has been philosophically embraced for its advantages, but physically adopting and operationalizing the model—particularly mid-flight on studies—require a commitment to overcoming fear of change. The model’s inherent flexibility will be instrumental to calming any concerns and will drive widespread adoption through 2021.

DCTs are each unique by design, and not one-size-fits-all. In contrast to the rigidity of traditional randomized control trials, DCTs offer a modular framework, affording choice to sponsors, sites, and patients. All stakeholders will become accustomed to having options. At that point, DCTs will no longer be a “nice to have,” but an expectation if not a stipulation of all protocols in the future. Just as we all appreciate and expect a personalized engagement in consumer activities—think online retail platforms such as Amazon—physicians, patients, and site teams should expect configurable and personal options for engagement that replicate consumer experience standards.

By the end of 2021, we will come to a tipping point where patients recognize how much less burdensome it is to participate in DCTs, sites recognize how technology enables rather than hinders such trials, and everyone appreciates how many ways sites and sponsors can save with this approach. The freedom to create trial designs that work best for each site, each patient, each protocol will be too great of a siren song—and will make DCTs easily scalable. The industry will not revert to the disjointed, manual, pre-COVID-19 way of conducting trials as progress so often requires abandoning long-standing behaviors to embrace the new.

Virtual Tools Will Expand Patient Access to Clinical Trials Tenfold

Jena Daniels, Director of Research and Head of Medable Patient Advocacy Council

Historically, access to clinical trials has been one of the greatest hindrances to study speed and success. By the end of 2021, many more pharmaceutical companies will leverage a DCT model, which will not only open doors to more patients but also reduce racial disparity in healthcare and improve overall outcomes.

Across the U.S., there is tacit acknowledgement of a two-tier system—those who have access to quality healthcare and those who do not. The difference between the two often tips the scales in terms of population representation in trials. DCTs improve access by bringing the trial to the patient, removing the burdens of travel and distance to make trials feasible across demographics. DCTs can also capture real-world data from patients “in the moment,” dramatically improving the quality of information.

This is not theoretical. The National Center for Biotechnology Information found that a DCT model recruited three times as many patients three times faster than the traditional model. The patients in the decentralized model also better represented urban and rural areas. These benefits are particularly important for rare diseases, as trials are few and far between and patients may be spread across wide geographic areas.

Also, expect to see diversity increasingly baked into study protocol design and early product development. This will extend beyond people of color to include different genders and ages. We will see patients from all backgrounds involved in the study process from the start. As an example, Medable’s Patient Advocacy Council (PAC) has patients ranging in age from 20 to their mid-70s, a mix of female and male members, and will expand its racial diversity in early 2021. The PAC informs Medable products and trial design—not on the back end, but at the beginning when they can make the biggest impact.

Improvements to Patient Care Will Trump Fear of the Unknown for Research Sites

Rasmus Hogreffe, Vice President of Decentralized Trial Innovation

The COVID-19 pandemic turbo-charged the use of virtual tools and a decentralized model for clinical research, but as life resumes more normalcy, the pharmaceuticals industry will continue its pace of adoption of DCTs. Investigator sites, which have been stuck between the “fear of missing out” and fear of the unknown, will cautiously push forward with DCTs as they see patients receiving better care.

It will not happen overnight, but sites will slowly have less trepidation as they see the impact that a decentralized approach has on patient care. DCTs allow patients to stay safely in their homes and still have physician-monitored access to potentially life-altering new therapies. Further, because patient health is surveilled continuously using wearables, electronic diaries, virtual check-ins, and other tools, they receive premier care. Sites can respond in real time and engage directly with patients more often.

Real-world data from in-the-moment patient accounts (before memory-muddled experiences are recounted at the next in-person visit weeks later) will also improve data quality and could lead to better outcomes. With greater trial access across all demographics, study data will be more comprehensive for greater insight into developing new treatments. The improvements in trial speed will drive more novel drugs to patients faster and for less cost.

DCT adoption will steadily increase through 2021 as improvements in patient care, data quality, and trial outcomes assure sites, sponsors, regulators, and patients that there is nothing to fear.

Digital Biomarkers Will Expose “Simmering” Symptoms Before They Turn Serious

Ingrid Oakley-Girvan, PhD, MPH, Senior Vice President of Research and Strategy

Tech-minded epidemiologists are working to crack the code of digital biomarkers as they could signal early and important changes in the trajectory of a disease. Researchers are now able to capture quality data, on a longitudinal scale, and harness the data across groups of patients to establish accurate markers. The fallout of COVID-19 has accelerated this effort as more companies take a decentralized approach to clinical trials and leverage remote data capture.

While the ability to capture digital biomarkers remotely is often constrained by cost and logistics, there are rich data that can be collected reliably with modern technology. For instance, a daily video that shows progressive changes to a Parkinson’s patient’s shuffle, a wearable device that measures hand tremors continuously, and a digital sleep monitor that tracks REM sleep cycles all inject new factors into the research equation to help determine accurate digital signatures. Just as critical, DCT platforms enable researchers to collect higher quality data from patients in their natural environment when they are most relaxed, eliminating the “white coat effect.”

As DCT adoption increases, science will be able to identify the early, “simmering” symptoms that could turn into adverse events later in the trial. Since the development of symptoms has the potential to jeopardize patient safety and instill fear and panic, patients could drop out of a trial prematurely. Identify these early, however, and the care team may be able to mitigate symptoms, prevent psychological harm, and avoid losing patient participation—especially if the incident was not caused by the investigative drug but by external factors, such as dehydration or lack of sleep.

In 2021, the momentum of DCTs and virtual technologies will allow clinicians and researchers to better identify digital biomarkers to help improve care and maintain the integrity of vital clinical trials. It will be the beginning of truly proactive patient care that is mindful of individual situations—the ultimate in long-promised personalized medicine and patient centricity.

Greater Access Will Drive Radical Improvements in Trial Efficiency and Effectiveness

Dr. Michelle Longmire, CEO and Cofounder of Medable

When I was a child, my father sought to rein in my gusto by saying “don’t put the cart before the horse.” So, when we founded this company and developed an early vision for DCTs, I resolved to curb my enthusiasm about the potential for this novel approach. Now, as an unimagined consequence of the pandemic, we are starting to see the impact that decentralization will have on trials—making them both more efficient and effective.

This past year, the decentralized model provided a vital stopgap to overcome the halt of clinical trials for thousands of shut-in patients and trial staff. What served as a band-aid in the short term quickly developed into a recognition that decentralized approaches can deliver a variety of benefits to sponsors, contract research organizations, sites, and patients. We saw faster enrollments and greater retention for patients participating from home. We saw more, and higher quality, real-world data. We saw more efficient processes and a dramatically improved patient experiences. We saw the resistance to digital and mobile technologies melt away, as televisits and remote screening and enrollment made participation easier for more patients from more places.

As the life sciences industry continues to march forward with its adoption of a decentralized model, it is incumbent upon technology providers like us to continue evolving our platform and solutions for even greater benefit. Companies simply will not go back to pre-pandemic ways. We will all continue to learn and innovate, and the domino effect will drive 50% to 70% increases in trial access and efficiency overall—ultimately leading to more effective therapies for more people around the world.

Medable, headquartered in Palo Alto, Calif., is on a mission to get effective therapies to patients faster by transforming clinical drug development with disruptive technologies for connecting patients, sites, and clinical trial teams to improve patient access, experience, and outcomes.