Pharma and biotech companies are shifting from traditional trial models to agile, patient-centric processes driven by digital technologies to improve R&D productivity. This evolution of the clinical trial was accelerated by the COVID-19 pandemic, where having remote monitoring and elements of decentralised, or virtual trials, became a necessity for keeping trials moving forward.
Now, amid an uncertain future, decentralised clinical trials are transforming the drug development landscape by leveraging digital technologies to improve recruitment and retention, data collection and analytics, while having the potential to increase cost efficiency. Other applications of digital technologies include automating processes, making efficient use of massive data sets, and supporting early decision-making with predictive analytics and statistical models.
A key component of the decentralised trial is the use of digital health technologies (DHT), an umbrella term used to describe wearables, connected devices and sensors used to capture physiological parameters directly from the patient. Yet, many barriers to adopting DHTs remain, including regulatory concerns, operational issues misalignment between internal stakeholders, data management, and statistical challenges. Avoiding these potential roadblocks starts with understanding how to successfully implement wearables and create meaningful digital endpoints.
Utilising DHTs in clinical trials without considering the impact on study participants or the role the wearable and its data has on outcomes – and whether they are meaningful to patients – can lead to an increase in patient burden. Further, poor selection of endpoints can drain resources by making interpretation and implementation of findings difficult or impossible, limiting evidence analysis and diminishing the value of the research.
In this article, we share how sponsors can innovate – from harnessing digital endpoints to employing virtual trials – to ultimately improve pharma R&D productivity, while better protecting patients.
The significance of wearables and digital endpoints
A growing use of smartphones, sensors and other consumer devices in a real-world setting has led to a trend in adapting these existing technologies for clinical research and the creation of digital endpoints that are quantitative, objective and continuous. There is increased interest in the use and value of digital endpoints in clinical studies, in parallel with a growing array of devices available to researchers. While the Apple Watch, Fitbit or Galaxy Watch were not initially developed for research use, they can produce useful information with respect to an individual’s physical behaviours. Increasingly, these devices are gaining credibility among the scientific community and are being used in clinical studies to track changes in physical activity and sleep patterns.
Engagement by tech companies with the FDA Precertification (Pre Cert) programme in the US has helped affirm their suitability as research tools. For these companies it is likely that clearance of their electrocardiogram applications, designed to detect signs of atrial fibrillation (AFib), has strengthened this credibility. The incorporation of photoplethysmography (ppg) sensors along with the standard accelerometers in these wearables is transforming them from mere fitness trackers into biosensors with the capability of measuring a large number of physiological parameters, including blood oxygenation – an important parameter for respiratory diseases including COVID-19.
As the adoption of wearables grows, more sponsors, clinical research organisations (CROs) and other stakeholders are demonstrating how DHTs can enable patient-centric measurement of health markers, such as physical activity, sleep, heart rate, medication adherence and respiration patterns/rate. Frequent and continuous monitoring – beyond the walls of the clinic – can offer more precise and accurate assessments than traditional observational assessments.
Moreover, sensors can capture existing measures in a new way, such as having a smart device or phone app to measure coughing, instead of relying on a patient to record episodes of coughing in a diary. In fact, a survey conducted by ICON in 2019 found that 70% of respondents preferred to use technology rather than paper for recording patient information.
Further, digital health technologies can be used to capture new measurements that would have previously been unimaginable. For example, a team at Johns Hopkins conducted an observational study requiring subjects to perform five cognitive tasks on a smartphone application, then merged the task data to form a validated mobile Parkinson’s disease (PD) score. Using a novel machine-learning approach, they demonstrated how this score complements standard PD measures by providing frequent, objective, real-world assessments that could enhance the clinical care and evaluation of therapeutics.
How patients benefit from DHT
For patients, DHTs such as wearables, sensors and implantables allow for data to be collected passively during their everyday life, minimising the need for clinical site attendance. As the burden of trial participation on patients and caregivers decreases, retention is improved, potentially reducing the time and costs of bringing new therapies to market. This benefit is reflected in a Clinical Trials Transformation Initiative (CTTI) study where 76% of respondents – with a median age of 61 years – reported they would prefer to participate in a decentralised study using mobile devices over a traditional one, citing greater convenience and fewer in-person visits. Respondents reported they were willing to use a variety of technologies – including mobile apps, wearable devices and ingestible sensors – provided they were comfortable, convenient and easy to use.
A strategy for successful digital transformation
Even though digital devices can be used in clinical trials it does not necessarily mean they should be incorporated. Sponsors will need to take the patient’s voice into consideration when deciding on study objectives, by first selecting digital endpoints that are meaningful to patients. Then, once the appropriate digital endpoint is identified, sponsors can consider the type of wearable or sensor that can provide the meaningful data. In some instances, endpoints may be focused on assessing improvement in everyday functioning, while in others, it will be about measuring stability or deterioration in a condition.
Implementing DHTs has unique challenges, including ensuring they meet standards for reliability and validity. To do this, sponsors should apply a framework for digital endpoint and device selection. CTTI recommendations include:
* Prioritising the patient – Sponsors should select measures with the patient in mind and capture insights that are not only clinically meaningful but are meaningful the patient
* Selecting the device – The process of device selection involves device identification patient acceptance testing, and technical usability and feasibility testing
* Managing operational excellence – As overlooking operational excellence can severely jeopardise the endpoint, sponsors must look at the end-to-end process holistically and implement risk contingency.
For any therapeutic area, the validation of a digital endpoint is a complex process. Using the framework that has evolved from proven clinical outcome assessment principles and techniques can help build the evidence required for submission to regulatory bodies and reimbursement stakeholders.
Successful implementation of wearables starts with partnership
Effective integration of digital devices into trial design, execution and reporting requires a strategic end-to-end approach. Sponsors will need to leverage the expertise of digital health technology and data science experts, along with patient-centred scientists, to develop a framework to map the process from device selection to endpoint validation. Establishing strategic partnerships with vendors who have a vast range of digital and innovation expertise, and who understand the regulatory landscape to successfully navigate cybersecurity and privacy issues, will be required to help develop the requisite tools that engage participants safely and effectively.
Marie McCarthy is senior director of Product Innovation at ICON plc
