Clinical trials are the universally accepted way of ensuring the safety of new pharmaceuticals and clinical treatments. But is there's room to innovate using wearable technology?
Clinical trials are the gold standard of medical compliance, a tried and tested way of making sure medicines, medical devices, and treatments are safe and effective. However, they also present challenges, such as the high financial cost, the need for ethical adherence, high failure rates, participant attrition and non-compliance, to name a few.
Writers such as Caroline Criado Perez have also highlighted how women are seen as a ‘confounding factor’ in clinical trials, leading to their exclusion or underrepresentation. Even where they are included, gender is not considered a variable, affecting the applicability of medical treatments to their bodies. And it’s not just women. In the US, people of colour make up 38% of the population but only 2 – 16% of patients in trials.
Wearables in clinical trials
In 2020 there were already 1,400 wearable studies underway, with around 540 completed. Keiser Associates and Intel have predicted that by 2025, 70% of clinical trials will incorporate sensors. Wearable sensors are being used to measure, among other things, heart rate, heart rate variability, glucose, blood pressure, movement dynamics, sleep patterns, skin and core body temperature. With an increasing number of these core measurements being benchmarked and qualified in wearables, new biomarkers linked to stress, sleep quality, cardiac conditions and UV exposure levels are also being evolved. The therapeutic areas that these studies mostly focused on were cardiovascular (the heart and circulatory system), neuroscience, respiratory diseases, sleep, stress, diabetes and obesity – in other words, the common conditions and areas that impact people’s health.
The advantages of using wearable tech are myriad. Clinical trials can most easily incorporate off the shelf wearables to monitor the above generic biomarkers, conduct some or all of the study remotely, and help with coordination. Within consumer health, for example, there is a need to develop strong scientific evidence to support claims. Dr Volker Spitzer, Global Sr. Director of R&D Services, Consumer Health at IQVIA, a global company creating innovation through connected intelligence in healthcare, explains why this is critical using the instance of the common cold:
“A typical example would be the tracking of the sleep patterns with a wearable when study participants are suffering from a common cold. The likelihood that sleep quality would be improved by using an established cough & cold medicine is quite high, however, currently it has not been proven by appropriate data. In this case, data recorded with a high-quality wearable device and related data algorithm could be the missing link to help prove a related claim or even new indication in this area. Without any doubt, the role of wearables will significantly increase in the near future, providing more relevant and new types of evidence, opening a new innovation area for the consumer health industry.”
In-depth and rich data is captured by these devices in real-time, providing an expansive backdrop to interpreting and systematising the outcomes of trials. According to a report by McKinsey, pharma companies and researchers increasingly are looking at ways to enhance the results of research and treatment options using real-world evidence, and wearables are an ideal way to capture that data.
Wearables could eliminate contextual biases or apprehension biases. The most commonly known of these is ‘white coat hypertension’, where blood pressure readings differ when taken by a clinician in a clinical setting because the patient has heightened anxiety. A wearable can potentially capture those readings in a natural setting, leading to greater accuracy. Given treatment regimes are based on biomarkers such as blood pressure, a trial adopting a wearable may ultimately lead to the conclusion that drug dosing be changed to reflect a better calibration through those trials.
Of course, the wearables would have to be designed to respond to diverse variables. Just as clinical trials can ‘design in’ biases, so can tech. For example, some examples of wearable tech offer less accurate reading of darker skin tones due to the limitations of photoplethysmographic (PPG) green light signalling in wearables, according to research.
Using AI and machine learning can assist significantly with the processing and analysis of data. Researchers can use nudge technologies to improve participant adherence and the correct positioning and use of wearable devices.
Where are we now?
The use of wearable tech in clinical trials is still at an early stage, but the potential disruptive and positive opportunity should not be underestimated. As with the consumer trend in the space, the signs are all pointing towards outcomes from trials with wearables. So far, many ‘off the shelf’ devices, such as Actigraph, Fitbit, Garmin and Apple have been prolifically used, but more novel and bespoke trial adapted versions are increasingly an option in the trial design stage. As Kate Lyden, Chief Science Officer at VivoSense Inc., specialists in utilising wearables to generate novel clinical trial data, says:
“Wearables provide an opportunity to develop a new class of objective and sensitive endpoints that are clinically relevant. Importantly, such tools can be deployed remotely, passively, and continuously, to generate large amounts of real-world data that reflect an individual patient’s lived experience and aspects of health that are important to patients and caregivers. VivoSense was founded in 2010 and though we have seen this movement gain significant momentum over the last decade, the Covid-19 pandemic has really kicked it into overdrive. It’s almost as if it has reminded us that when it comes to healthcare and clinical trials, we can do things differently.”
One example of how these wearables are being used is the Heartline™ Study. The trial emerged from a collaboration between Apple and Janssen Pharmaceuticals, which resulted in a three-year research study in 2020 to use Apple’s irregular rhythm notifications and ECG app to improve the early detection of atrial fibrillation (AFib) in the over 65s. AFib affects 33 million people worldwide and is a leading cause of stroke. The study, managed through an app connected to an Apple Watch, allows people to engage in the trial remotely.
It followed on from another collaboration between Apple and Stanford University called the Apple Heart Study, with the results published in the New England Journal of Medicine in 2019. Participants without AFib used an app to detect irregular heart rhythms. If the smartwatch-based irregular pulse notification algorithm detected a trigger, a clinical response was initiated, such as a telemedicine and an electrocardiography (ECG) patch mailed to the participant. Two thousand participants (0.5% of the trial) were notified of an irregular pulse, and of these, a quarter wore an ECG patch and completed the protocol. Of this latter group, 84% were confirmed to have AFib. While it may take a while to filter through to clinical practice, it has enormous implications for health monitoring.
The Memorial Sloan Kettering Cancer Centre (MSK) in the US partnered with Medidata to assess whether wearable sensors and mobile tech could help improve myeloma patients’ quality of life. Participants self-reported quality of life metrics such as activity level, fatigue and appetite. They also wore a Garmin Vivofit® (GV) fitness tracker to provide insight into patterns of activity and sleep. The trial successfully reported that passive wearable monitoring can successfully capture patient activity and has a significant therapeutic application, potentially enabling a better quality of life for patients.
It is an uncontroversial good that clinical trials are highly regulated. The downside of that regulation is slow and limited adoption of new technologies, particularly when benchmarking existing or new biomarkers for inclusion in clinical studies.
There is an uneasy mismatch between the purposes of tech companies and clinicians. As Janson and Thornton argued in 2019, there is a strong need for more collaborative relationships between tech companies, clinicians, researchers and regulators to make and adapt devices for use in diverse clinical trials. As Independent Healthcare and Medtech Growth Consultant Steve Parr puts it: “Given the years and millions of dollars it typically takes to develop a new drug, and the high trial failure rate in some areas, it seems odd that clinical trials have yet to take full advantage of digital biomarkers.”
However, the current pandemic has shown the potential of public/private collaborations that may carry over into future research and innovation. And with this immense mobilisation of effort has come renewed interest from tech companies in analysing health data to improve health and social problems. An example is the six-second walk test to assess walking capacity in Parkinson’s patients. It is a biomarker known and used by all clinicians. Wearables that track movement could offer real-time, granular data to give a much richer picture of movement dynamics and the potential for variable treatment regimes. Parr says:
“Focusing on clinical endpoints and using well designed non-invasive wearable technology can provide trial programmes with real-time monitoring and millions of real world data points from a patient each day. As well as improving data quality and trial effectiveness, this approach also improves patient recruitment and retention.”
Jacob Skinner, CEO of Thrive, says clinical trials need a third way between greater bespoke functionality than an off-the-shelf wearable would offer, while still being relatively cost-effective. That’s where companies like Thrive come in.
“We help companies design systems with a combination of configured sensors, tuned into a given trial design requirement”, he says. “There are often misconceptions in terms of the barriers to developing solutions like this, but as these building blocks become more qualified and reusable, we are seeing an increase in interest across the board. We have developed pre-clinical trial systems in three months, which is incredibly fast.”
As already outlined, participant adherence, attrition and misuse of wearable devices in trials is an ongoing practical problem, which can seriously affect the reliability and validity of data. However, tech companies like Thrive can help solve these issues through quality design and strategic capability. Built-in sensors can report and alert the user if a device is incorrectly positioned. Good design can also help alleviate problems. Take wearables worn on the wrist: designers can build a ratchet clasp to tighten to the correct fitting automatically. The sensor surface can be bigger or more accurately curved to create a better fit.
Thrive has the expertise and tools to rapidly design and produce bespoke, low-cost wearable technology that will accurately track the biomarkers required for individual clinical challenges, uniquely configured for that particular challenge, and delivered in a user-friendly form.
Wearables look set to transform the landscape of clinical trials, delivering richer results more efficiently and with considerable potential cost-savings. With the potential to significantly improve trial outcomes, creating better medicines and interventions, save lives and enhance the quality of life. We are very positive about the progress being made in between innovators, clinicians, researchers and regulators. It is now very clear that embracing wearable technology in trial design is already offering transformative benefits to all stakeholders.