Part 1: Fueling Fast Growth of Hybrid and Fully Decentralized Research

Flexibility Inherent in a Decentralized Trial Model Will Drive Widespread Adoption

The promised decentralized trial revolution has gained traction in 2020, but we have significant progress to make. Industry wide, the decentralized approach to clinical trials is philosophically embraced for all its advantages but operationalizing the model–particularly mid-flight on studies–requires 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 controlled trials, DCTs offer a modular framework, affording choice to sponsors, sites, and patients. All stakeholders will become accustomed to having options; in fact, they will expect them. At that point, DCTs will no longer be a “nice to have” but rather an expectation (if not a stipulation) of all protocols in the future. Just as we all appreciate and expect a personalized engagement in consumer experiences (think of 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, how technology enables rather than hinders, and 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, or each protocol will be too great an attraction – and will also make DCTs easily scalable. Industry will not revert to the disjointed, manual, pre-COVID way of conducting trials; progress so often requires abandoning long-standing behaviors to embrace the new.

Decentralized Clinical Trials Will Enhance Patient Care and Drive Study Participation

As decentralized clinical trials become standard, the next big hurdle will be learning how to adapt to data received daily in real-time. We will need to answer, “How do we verify the quality of data collected remotely?” and “How do we respond digitally to the speed of change?” It will be a shift. We will need to identify new best practices that will offset traditional activities, such as acclimating CRAs and study safety teams to seeing the data daily, as they are collected, and reviewing them from home (or anywhere) digitally rather than waiting to review study data weekly, or monthly, in person, at study sites.

Just as importantly, healthcare professionals will need to learn to engage with patients more frequently, at times remotely, to ensure the patient’s health is being actively monitored and nurtured, and to ensure the integrity of the data being collected. Trial participants will receive the gold standard of care, which will lead more patients to view trial participation as an effective healthcare option. Instead of viewing clinical trials and pharmaceutical development with skepticism, patients will see trials as a vehicle to receive top-rate care and as engagement in the development of breakthrough medicines.

For all this to come together, however, DCTs must be built on a unified platform where all trial data are reported and are visible to all stakeholders in one system. Sites must be alerted when patients input their data and respond in real time for the “ultimate in patient-centricity.” By the end of 2021, decentralized trials managed on a unified platform will thrive and garner greater trial participation, speeding up clinical trial timelines and accelerating the speed of drug development.

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

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

While the digital biomarkers that can be captured remotely are 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 in the shuffle of a Parkinson’s patient, a wearable device that measures hand tremors continuously, or a digital sleep monitor that tracks REM sleep cycles all inject new factors into the research equation to help determine accurate digital signatures. Critically, DCT platforms enable researchers to collect higher quality data from patients in their natural environment when they are most relaxed and eliminate the “white coat effect.”

As DCT adoption increases, science will soon be able to identify the early “simmering” symptoms that could turn into an adverse event later in the trial. Development of adverse symptoms has the potential to jeopardize patient safety and instill fear if not panic in patients who might then wish to drop out of a trial prematurely. Identify these symptoms early, however, and the care team may be able to rapidly mitigate them, prevent psychological harm caused by them, and avoid losing patient participation – especially if the incident was not caused by the investigational drug but rather 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 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.

Industry Will Align on Master Protocols

In 2006, the unprecedented approval of Novartis’ imatinib mesylate for five new indications based on a single phase 2 clinical trial bewildered the pharmaceutical sector. FDA not only approved a drug without the customary two pivotal phase 3 trials, but the drug was also cleared to treat a record number of cancers based on an open-label, single arm prospective study that enrolled just 186 patients with 40 malignancies. In five of 40 malignancies, the responses were robust, and they became the basis of the NDA applications and subsequent approvals. Remarkably, most of the studied groups had ten patients or less. At the time, many had wondered how Novartis accomplished so much with so little.

The imatinib story is an illustration of the biomarker-driven precision medicine trial designed using the principles of master protocols. What was once used exclusively for oncology trials is now used for other conditions such as Alzheimer’s disease and pneumonia. Since 2006, the growth of master protocol studies reflects the shift in focus to targeted therapies for difficult to treat conditions, to genomics, and to personalized healthcare. Innovative trial designs, particularly DCTs, will drive the use of master protocols in more therapeutic areas by the end of 2021.

Many patient advocacy groups support the use of master protocols, mostly because they increase patient access and reduce the burden for all stakeholders by pre-contemplating important factors and building them into protocol design from the start. While this approach requires more up-front work, it is more than offset by the efficiency gains at the back end. For example, there are fewer administrative burdens for sites, patients are more likely to stay on the trial, and knowledge is gained more rapidly.

As we move through 2021, expect pharmaceutical companies, patients, sites, and regulators to align on greater use of master protocols. Remote technologies so key to DCTs will enable their use as well as make studies more adaptable, which benefits all stakeholders. Ultimately, this will help cut cycle times in half and allow researchers to collect more robust data, in and out of the clinic, with much less burden on patients and sponsors/sites.

Greater Access Will Drive Radical Improvements in Trial Efficiency and Effectiveness

As an unimagined consequence of the pandemic, the entire life sciences industry is starting to see the sizable impact that decentralization has on trials – making them both more efficient and more effective.

In 2020, 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 recognition that decentralization offers a variety of benefits to sponsors, CROs, sites, and patients. We saw faster enrollments and greater retention of patients participating from home. We saw more and higher quality real-world data. We saw more efficient processes and a dramatically improved patient experience. 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 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 50-70 percent increases in trial access and efficiency overall, ultimately leading to more effective therapies for more people around the world.