Special Section: Cancer Moonshot – Five Years and Rising

image of a cancer cell
Digital Therapeutics Deliver Surprising New Benefits for Cancer Patients
Leveraging Hybrid Decentralized Clinical Trial Model Speeds Go-to-Market
Joel Morse
Curavit Clinical Research

igital technologies have had profound effects on how we communicate (i.e., smartphones), share information (i.e., social media), and create (i.e., 2- and 3-D printing). Now, they are having an impact in healthcare, too. The latest (and arguably most exciting) example is digital therapeutics (DTx): medical treatments to address health conditions via a combination of software and communications. DTx are in use or being tested for a growing list of diseases and conditions: Type 2 diabetes, congestive heart failure, obesity, Alzheimer’s disease, dementia, asthma, substance abuse, hypertension, anxiety, depression, and more.

Digital Health or Digital Therapeutics?

Researchers and policymakers make distinctions among digital health (the overall category of health-related interactions), prescription digital therapeutics (apps or tools that have gained regulatory approval), and software used as an adjunct to guide a healthcare provider’s treatment of a patient (software as a medical device, or SaMD, regulated in the US by the FDA Center for Devices and Radiological Health). There are overlaps from one category to another but, in nearly all cases, a rigorous evaluation in the form of a clinical trial to clearly demonstrate the impact of the digital technology is needed, even when regulatory approval is not the end goal.

“Digital solutions have a variety of intended use cases which drive their approval pathway, and they are equally valuable and important depending on the end goal,” said the head of digital health, oncology R&D at a top-10 pharmaceutical company that has digital therapeutics in development across therapeutic areas. “Whether the digital therapeutic is for consumer health assessment or in a trial or routine care setting, following the guidance around use cases and a carefully developed measurement framework is critical to ensure scientifically rigorous and responsible assessment of a patient’s health status.”

In parallel with the maturation of DTx, numerous researchers have been examining the social or patient-centered aspects of oncology care, especially now that oncology care is becoming a participant in the DTx evolution. The opportunities for improving health outcomes in oncology through DTx arise from challenges expressed by many cancer patients: surgery, radiation, chemotherapy, and/or immuno-oncology, all carried out over several years and with substantial side effects. Sleep, eating patterns, and physical activity can be affected. For many patients, simply withstanding the course of treatment is a victory, let alone what happens to their cancer.

Researchers think that digital therapeutics can help. One pre-market prescription DTx company dedicated to improving mental health in cancer patients is conducting various clinical trials on new DTx products designed to improve cancer-related distress that affects a patient’s quality of life or ability to cope with cancer diagnosis and treatment, which affects nearly half of cancer patients. According to the company, “digital therapeutics that help to treat cancer-related distress have the potential to help close the cancer treatment gap.” DTx products may incorporate cognitive behavioral stress management, which has been tailored to cancer patients and shown in numerous clinical studies to improve emotional well-being, physical health, and overall survival.

“We will continue to prioritize the study and development of digital therapeutics for real-time, continuous patient monitoring, from side effects of treatment to symptoms of disease that indicate progression. The aim is to allow patients to stay on therapy longer, have fewer side effects and adverse events, wherein this improved treatment tolerability may potentially lead to increased benefit from therapy,” added one top-10 pharmaceutical company’s head of digital health.

For at least the past decade, researchers have been documenting longer survivals, better adherence to therapy, and improved quality of life (QoL) when various forms of digitized health or therapeutic actions are taken. A lung cancer study comparing symptom monitoring using a DTx versus the standard process conducted in France in 2017 was so successful that it was prematurely halted and patients in the control group were transferred to the study group receiving the digital intervention. The median overall survival was 22.5 months in the digital intervention group versus 14.9 months in the control group.

Another app-based symptom reporting study at Memorial Sloan Kettering found a five-month extension of median overall survival among solid-tumor cancer patients, along with improvements in QoL during treatment. “One potential mechanism of action is early responsiveness to patient symptoms preventing adverse downstream consequences,” the researchers summarized.

Despite these early successes, organizations often must run clinical trials to reinforce the value of digital intervention to all stakeholders including not just regulators, doctors, and patients but also payers, who seek health economics data. DTx manufacturers are increasingly leaning into the decentralized clinical trial (DCT) model for its speed, efficiency, data quality, and patient-centric advantages.

Now a widely accepted trial model in the aftermath of the COVID-19 pandemic, DCTs use software to connect patients to trials. Travel to and from the trial site is minimized or eliminated; interaction with trial participants can be frequent (or, in cases where wearable medical devices are involved, it can be 24/7); and there are few geographic limitations, so participation can be more representative of the population.

In addition, there is a fundamental alignment between a DTx and a DCT. Since DTx is software rather than an oral or injectable formulation, there is no physical distribution or administering of medicines, just as there are often no physical sites in a DCT. There are no logistics: No shipping, storing, chain of control, cold storage, or biohazards; in addition, endpoints can be captured within the DTx application itself, making DCTs ideally suited for DTx studies. In the case of combination DTx/traditional studies in oncology, however, there will likely need to be some in-person site visits, so a “hybrid DCT” approach may be ideal.

Here are three key benefits of hybrid DCTs in oncology DTx development:

DCTs Boost Patient Recruitment, Retention, and Engagement

Patient retention and engagement have long been challenges in clinical research, but DCTs have had a uniquely positive impact on digital therapeutics studies. DCTs make participating in research easier and studies more accessible to participants who live far away from study centers or are unable to visit trial sites for various reasons. Without the need to perform all assessments at a clinical trial site, sponsors can successfully recruit patients from greatly expanded geographic areas. Opening studies up to more participants optimizes the patient pool and reduces the need to overenroll based on anticipated attrition or dropout rates.

Decentralization Improves Cost Efficiency

DCTs save costs, in part, by saving time. For instance, the single biggest time drain in drug clinical trials is patient recruitment, which can take about one-third or more of the duration of the entire trial and contributes to a trial’s high price tag. Similarly, recruiting a diverse patient population and keeping them engaged for DTx studies is draining. By expanding the geographic area for recruitment, DCTs speed recruitment across a more representative patient population. By removing many of the burdens associated with traditional trials, DCTs decrease dropout rates in DTx studies.

In addition to the financial benefit that comes from saving time, DCTs require less staffing and greatly reduce the need for sites and infrastructure. In fact, for many growing DTx companies, lengthy brick-and-mortar trials are unnecessary because they don’t have the same scope or needs as a randomized phase 2 or phase 3 study. The technology that DTx companies need to run a trial is materially different from the technology needed for a traditional drug trial. Further, much of the software needed for a DTx trial is already baked into the DTx app used in the study, so many of the components (such as EDC software) required for traditional clinical trials involving prescription drugs are not needed. This is not to suggest that a decentralized clinical trial is any less valid–just more innately streamlined. As a result, DTx companies can save substantially–reducing the costs by a factor of 20 or more–by picking just the technology needed rather than paying for complete functionality of an application or irrelevant bells and whistles.

This benefits the patient, too. Patients who use one app to complete all trial forms find participation much easier than using different devices or going into a site for repeat visits. Again, a better patient experience decreases study dropout rates and results in even greater savings and improved trial data.

Data Quality Improves with DCTs

DCTs enable DTx companies to collect real-world data directly from patients where they are most comfortable, minimizing the “white coat” effect, which has a quantifiable impact on data quality in the form of increased blood pressure in response to a clinician visit. Having a wider (more diverse) trial population means that the data collected are more reflective of real-world conditions; moreover, the potential for more precise data collection from patient interactions can translate into more granular data analysis.

“Digital therapeutics are prescribed by a doctor often alongside a medicine, so it’s very reasonable to expect that we’ll see more DTx and drug combination regimens emerge in oncology in coming years,” concluded one top-10 pharmaceutical company’s digital health leader. “Combining innovative new treatments with evidence-based digital health solutions is one way we can think more holistically about cancer patient care to improve health outcomes.”