Finding a balance: Blending traditional and digital clinical trials for DTx

It seems to be in our nature to think of things as binary: you prefer the beach over the mountains; you like sweet treats rather than salty; this is correct and that is wrong. But such black-and-white thinking does not always serve our purpose well. Sometimes it’s simply not a zero-sum game.

When COVID-19 forced many white-collar employees to work remotely in March 2020, business leaders feared the worst. Productivity would crater, they thought, and trying to bring employees back to the office after a long absence would be impossible. Yet, those fears have mostly not come to pass because both employers and employees saw the value in moving towards hybrid work environments. Now, more than three years later, almost three quarters of US companies offer their employees a hybrid work environment that combines both in-person and remote work options. It’s the best of both worlds.   

A new paradigm in clinical research

This same kind of thinking should be employed when considering clinical trials as well. Decentralised clinical trials (DCTs) gained popularity in much the same way that remote work did - out of necessity. During the pandemic, sponsors simply had no other option if they wanted to conduct a trial. And although traditional clinical trials are now available to sponsors again as COVID-19 dissipates, sponsors see the important advantages that the decentralised approach offers. So, why not combine the best of both? If office workers can do it, so can forward-thinking clinical trial sponsors. 

However, to successfully embrace a hybrid approach to clinical trials, sponsors need to deeply understand their objectives, and then choose the right mix of decentralised versus in-person trial elements. If done correctly, clinical trials that are designed with digital-first principles, but which also include a strategically considered site visit component, could become the gold standard in clinical research, much the same way that hybrid work has become commonplace in a post-pandemic environment. 
 
Nowhere is this new paradigm in clinical research more likely to become a reality than in digital therapeutics (DTx), an area of healthcare that is growing fast. While still a young sector, the DTx market is projected to grow 21.54% to reach $20 billion by 2029. Because of high incidences of chronic disease and mental health issues, along with rising demand for controlled healthcare facilities and treatment cost, demand for DTx has skyrocketed and the industry has responded by investing generously. There are now eight DTx unicorns globally. 

DTx and leveraging DCTs and traditional site models

Given that DTx are software-driven and therefore can be more easily delivered to participants regardless of their location or circumstances, these products are well-suited to the decentralised trial model. And because of its flexibility, DCTs can greatly improve participant enrolment, retention, and engagement. There are no physical logistics – no shipping, storing, chain of control, cold storage, or biohazards, plus endpoints can be captured within the DTx application itself, making DCTs ideally suited for DTx studies, whether seeking regulatory approval or to bolster consumer and payer confidence. And because the DTx being studied can double as the data collection device, manufacturers often don’t need costly extra technologies like an ePRO. 

Even with these advantages, DTx products can sometimes face an increased level of scrutiny in trials, and the patient screening process may require a physical engagement with a healthcare professional. Further, some DTx companies want to supplement data from the device with more traditionally collected metrics to create fuller evidence packages to meet needs of diverse stakeholders, be it regulators, payers, or doctors. As such, DTx companies see enormous value in leveraging elements of the traditional site model alongside a decentralised approach. Incorporating some in-person clinician visits can lend a greater sense of legitimacy to sceptical physicians and provide peace of mind to all. 

“One of the exciting things about new technology, as well as one of the challenges, is that it really opens up new ways to develop products,” said Mike Rosenbluth, PhD, CEO at DTx company Swing Therapeutics. “Many of the processes of developing a drug are not relevant for DTx, so we’re committed to evidence development and demonstrating that our products are clinically effective – the industry needs to build on a solid foundation of evidence, so that digital therapies can be adopted as standard of care.” 

Nascent therapeutics and market access complexity

Moreover, although DTx companies are producing remarkable, life-changing therapies, commercialisation has proven challenging. These nascent therapeutics often get mired in commercial processes that were originally designed for traditional therapeutics, and face market access complexity. Healthcare codes are an important part of the problem, too, for prescription and non-prescription DTx alike. These include CPT (Current Procedure Terminology) and the HCPCS (Healthcare Common Procedure Coding System). Just as product SKUs revolutionised both early supply chain management and modern e-commerce, diagnosis and billing codes are needed to unlock DTx uptake. And while a limited number exist, there is a lack of standardisation - and, manufacturers would argue, variety - to scale DTx use.

A fresh approach to clinical trials enables prescription DTx (PDTx), so as to ensure that their products can successfully navigate the regulatory process with greater ease, while also providing evidence of safety and efficacy to increase the likelihood of payer coverage, which has been a hurdle to adoption of DTx products to date (and an issue that led to the bankruptcy of Pear Therapeutics in April 2023).

“Being able to deploy and demonstrate adequate risk mitigation measures in hybrid and decentralised trials helps to assure patients, healthcare providers, and health insurers of the safety and reliability of treatment in the home or community,” explained Sabrina Taylor, PhD, CCRP, head of clinical trials at MedRhythms, a DTx company that has adopted the hybrid clinical trial model for its neurotherapeutic designs to improve walking, mobility, and related functional outcomes by using a technology platform that combines sensors, software, and music with advanced neuroscience to target neural circuitry. The company is developing a pipeline of digital therapeutics across a range of neurological conditions, including stroke, multiple sclerosis, and Parkinson’s disease. To capture safety and efficacy data across various indications, MedRhythms is leaning into the more cost-efficient DCT model and incorporating requisite in-person site visits to supplement data collection. 

“One of the primary benefits of hybrid and decentralised clinical trials is their ability to increase patient access to research opportunities,” added Dr Taylor. “Plus, considering the care context serves as a useful guide when identifying the aspects of the study that must be completed in person and those that may be conducted virtually. This helps clarify the role and requirements of collaborating research sites and can be completed early in the study-planning process.” 

An intersection of trial designs

Success will be achieved by the organisations that can properly identify where decentralised and traditional study designs intersect. The situation is complex, and the answer could be different even for the same patient. But, as more DTx companies begin to deploy the hybrid trial model, they will begin to find a mix of trial strategies that serve their purposes and act as roadmaps for others to follow. 

“Many DTx companies develop products where the majority, if not all, of the interaction points between a company and a patient occur outside of the clinic,” Dr Taylor concluded. “Because of this, at-home data collection is a natural part of these companies’ DNA. It seems that this familiarity, combined with the cost savings, make alternative study designs a good fit for the DTx market.”

In short, find the right trial blend, and the DTx industry could revolutionise clinical trials for everyone.