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Before the pandemic, a December 2019 Industry Standard Research survey found that 38% of pharmaceutical sponsors and contract research organizations (CROs) expected virtual trials to be a major component of their portfolios, and 48% expected to run a trial with most activities conducted in participants’ homes. One year later when attendees at McKinsey’s Clinical Operations Roundtable were asked the same questions, the responses were 100% and 89%, respectively.
Today, most are asking what trials and what aspects of trials can be effectively decentralized and to what degree. Fully virtual or decentralized clinical trials (DCTs) typically handle all enrollment processes and assessments in a patient’s home, enabled by end-to-end digital tools and involve the self-administration of medicines. This model is gradually migrating from smaller, early-phase and post-approval studies toward larger pivotal trials, such as Otsuka and Click Therapeutics’ landmark fully remote clinical trial to investigate the effectiveness of digital therapeutics in reducing symptoms in adults diagnosed with major depressive disorder (announced in Feb 2021).
In the near term, sponsors, investigators, and CROs expect fully virtual trials to remain limited to a narrow set of use cases, such as a well-characterized drug with few adverse events in a mild indication, with end points suited to remote measurement. Long-term, however, fully virtual trials will be more widespread—especially in certain therapeutic areas such as rare disease, mental health, central nervous system, neurodegenerative and others that require patient populations that can’t physically travel or don’t live near a site.
Ultimately, the therapeutic area alone shouldn’t determine a trial design. Rather, each trial should be designed for-purpose and centered on patients. The target patient population, treatment, and indication will primarily determine whether a trial is fully virtual, hybrid or a traditional site-based trial. Even so, there are defining patient population characteristics in many therapeutic areas that can make some studies more likely candidates for all-virtual research.
Here are five therapeutic areas that are particularly apt for an all-virtual research approach, and that can serve as an entry point for hesitant sponsors interested in exploring this growing DCT model.
Diabetes—More than one in 10 Americans have diabetes and one in three or 88 million adults are prediabetic. Given the disease’s prevalence and its widespread geographic reach including many rural areas, diabetes is ripe for fully virtual research. Blood glucose values can be monitored continuously with wearable devices attached to the patient’s skin and automatically uploaded to a central platform in the cloud for easy access by trial investigators, sponsors, and the patients themselves.
In addition, the propensity of patients with Type two diabetes to be elderly or struggle with obesity can make it difficult for patients to travel to trial sites. These patients often have vascular problems which also can also hinder mobility. Further, diabetes is rampant in certain demographics such as Native Americans who are twice as likely to have diabetes as whites and often live in remote rural areas far away from the nearest clinician. Virtual trials bring lifesaving treatment to these patients and further the development of treatments that reflect the unique needs of a more representative population.
Cardiovascular—With wearable devices, including Apple watches, that monitor increasingly more sophisticated and wider range of cardiovascular endpoints remotely, research focused on cardiovascular diseases are apt for a fully virtual trial design. These devices accurately monitor and measure cardiac events and catch issues, such as atrial fibrillation (a common type of sustained cardiac arrhythmia) and ventricular tachycardia (abnormally fast heart rate) to alert the patient and remote physician in real time. Even some clothing items, such as bras, have sewn-in heart monitors! There are other devices that can be worn continuously for months at a time to capture more sophisticated measurements and automatically send data into the cloud. The same is true when it comes to managing blood pressure.
Like diabetes, cardiac patients are in all corners of the world and often many hours from central research sites and—due to their condition—may have mobility challenges and concerns. Virtual trials extend access to the millions living with heart disease and high blood pressure. Further, the data gained from continuous and multiple-symptom monitoring of cardiac patients is dramatically more useful in comparison to the less-reliable, one-hour, single-symptom testing completed at a site once a month or every few months. Heart arrhythmia often occurs only intermittently so it may not be picked up at the occasional site visit. Today’s wearable devices monitor blood pressure, heart rate and rhythm, and oxygen saturation levels as well as activity level (steps taken) so researchers can superimpose different measurements depending on what endpoint is being studied or combine multiple measurements for more meaningful information.
Central nervous system (CNS) diseases—Parkinson’s Disease, Multiple Sclerosis, Alzheimer’s disease, and other CNS diseases may dramatically impact patients’ mobility as well as hamper caregivers’ ability to bring affected loved ones to frequent clinician visits. All-virtual trials open these patients up to potential opportunities they might not otherwise ever have for a treatment.
Like cardiac wearable devices, there are an increasing number of new technologies that allow researchers to measure novel endpoints of patients in the comfort of their own homes and in more realistic life settings outside of a doctor’s office. Devices can continuously measure number of hand tremors per minute, for example, so a novel endpoint could be the reduction of hand tremors which was not as easily studied in traditional trials.
An electroencephalogram (EEG) is a widely used non-invasive method for monitoring the brain but has historically been a large and bulky technology, restricted to the monitoring of subjects in a lab or clinic while they are stationary. Today, we can use a wearable EEG, which overcomes these limitations and allows the long-term, non-invasive recording of brain signals at home.
Neuromuscular trials—Like patients with CNS disorders, patients struggling with neuromuscular diseases, including Duchene Muscular Dystrophy may have severe mobility challenges that make it difficult to make regular clinician visits. Fortunately, there are advanced activity monitors that do not interfere with movement on these patients such as ankle bracelets that can record various measurements continuously to, say, show how much activity a person takes part in over a period. Red Nucleus Clinical’s iTakeControl platform is a clinically approved solution that enables HIPAA-compliant video assessments of patients, live video research visits and audio recording to provide richer audio/visual data that is also auditable for compliance purposes.
“We have used our platform in various ways across different clinical trials, but it has proven particularly effective in trials of boys with Duchenne Muscular Dystrophy,” explained Chris Jones, partner at Red Nucleus. “Rather than forcing parents to spend hours on the road or in flight for site visits, leaving everyone exhausted, iTakeControl platform allows parents to administer video patient assessments at home that can be reviewed by an objective clinician and quantified as clinical evidence.”
According to Jones, the video assessments also provide recorded evidence that can be compared over time to assess change. This is especially important in neuromuscular disorders where changes can be ambiguous or imperceptible to an untrained eye. Disease area expert researchers can review the videos to look for the smallest fluctuation in movement or function. “We can assess and compare pediatric developmental milestones, like communicating or playing with blocks, over time,” he added.
The technology has also been used to assess validated instruments, such as the Clinician Global Impression of Change or Severity, for real-world function data that is meaningful to the trial. “We can also conduct live video tele-research visits between researchers and participants and their caregivers within a GCP-compliant application that includes components seamlessly integrated with the study including an audit trail and recording options,” explained Jones.
Pulmonary disease and sleep disorders—Chronic obstructive pulmonary disease (COPD), asthma, and other pulmonary diseases share common characteristics that lend themselves to fully virtual trials. Virtual Contract Research Organizations (VCROs) can engage patients through central virtual sites and leverage advanced HIPPA-compliant technology platforms to capture all necessary information that’s automatically uploaded in the cloud. This is especially prevalent for patient recruitment, where remote coordinators (nurses, principal investigators, research assistants) engage with patients via telemedicine or secure video to interview patients and review medical records to determine trial eligibility and obtain informed consent.
Remote monitors can be worn by pulmonary patients to capture breathing patterns, coughing episodes, and oxygen saturation measurements in real time and continuously for more meaningful information. Additionally, patients can use clinically compliant apps on their mobile devices to record how they are feeling compared to using clunky paper questionnaires. These apps can be programmed to remind patients to complete their ‘homework’ to reduce the burden and use symbols or leverage games to help pediatric patients comply. All collected information from the app will then be fed into the central virtual site platform for review by the research team, yet the patient never leaves the comfort of their home.
The same is true for sleep disorders like sleep apnea or insomnia. Connected devices that monitor oxygen saturation can be used anywhere and the data collected can be automatically uploaded to the cloud. Withings, for example, has a clinically compliant Sleep Tracking Mat that tracks and analyzes sleep cycles (deep, light and REM), heart rate, and snoring. Withings can also monitor the intensity of breathing disturbances, thanks to an algorithm that analyzes interruptions in breathing patterns that occur during the night. Patients not only benefit from staying in their own homes during a trial but also see their own symptoms’ impact on night sleeping.
Today, nearly every therapeutic area performs clinical research where at least some aspects can be decentralized. Even certain aspects of complex oncology trials can be decentralized to improve patient access and data capture. For instance, the National Cancer Institute’s Cancer Moonshot program funded a DCT managed by Medable calledthe Digital Biomarkers for Clinical Impact (DigiBioMarC) study. This study aims to understand and improve the quality of life for patients receiving cancer therapy.
Even so, DCTs are still relatively new to many life sciences sponsors and researchers, causing some companies to be cautious. The COVID-19 pandemic forced many companies to leverage more virtual approaches to research, and many promise that there is “no going back” to traditional trials. The advantages that research virtualization can bring to key therapeutic areas must be carefully considered by each sponsor, researcher, CRO, and academic institution as they evaluate what approach, or combination of approaches, is most effective for their purpose.
As the industry becomes increasingly comfortable and knowledgeable about virtual research and DCTs, this new model will become more mainstream. The advantages to both researcher—i.e., faster patient enrollment, richer real-world data, use of digital biomarkers—and patient—i.e., more access to life-changing treatments, less burden, faster results—are simply too important to ignore.
“Globally, the clinical research landscape will increasingly incorporate new technologies into their trials,” concluded Jones. “COVID cracked open a new mindset across the entire life sciences industry where even the wary are embracing digital innovation to advance healthcare. The future looks bright.”
Dr. Pam Diamond is Co-founder and Chief Medical Officer of Curavit Clinical Research