Patient-Centric DCTs Elevate Engagement and Yield New Scientific Insight
Digital tools are often at the core of decentralised research. Why are they so integral to successful of research, and how might this continue to develop?
By Bruce Hellman
Chief Patient Officer and Co-Founder of uMotif
Decentralised clinical trials (DCTs) took centre stage during the COVID-19 pandemic, revealing their effectiveness in advancing life-saving research and the development of new treatments and therapies during such unprecedented circumstances. Buoyed by the immediate impact and future potential of DCTs, the FDA has since signalled its continued support for this evolving format.
DCTs can take many forms, from completely virtual to various hybrid models. The common thread that binds them is the use of digital tools to navigate and support the clinical trial lifecycle, which encompasses enrolment, consent, monitoring, and data collection.
The use of technology reduces and sometimes eliminates the need for frequent trips to trial centres and clinics. These visits, a routine part of traditional clinical trials, can place a significant burden on patients and caregivers, hindering recruitment, engagement, and retention.
The industry is beginning to document the impact of DCTs. A 2021 study of clinical trial professionals found (1):
• 70% of respondents have been involved in or worked on trials that have implemented some decentralised element in the last two years
• 58% say DCTs are faster than traditional trials, saving on average three months from start to completion
• 71% say DCTs are better for patient recruitment
• 74% say DCTs are better for patient retention
DCTs can transform research in another powerful way: by using remote technology. Diverse Electronic Clinical Outcome Assessment (eCOA) and Electronic Patient-Reported Outcome (ePRO) solutions, wearable sensors, and home sample collection mean researchers can capture more timely, contextual, and diverse data than is possible with traditional site-based trials. This data, which includes rich qualitative and outcome-focused input, can empower researchers to answer questions they could not answer before, filling important gaps in scientific knowledge. For example, researchers have long struggled to understand the real-world impact of hypoglycaemia (very low levels of blood glucose) on individuals with Type 1 diabetes, due to historical site-based research constraints. Digital technology opens the door to understanding these key questions in diabetes, as well as many more health conditions.
Decentralised Clinical Trial Success – The Human Connection
While DCTs have great potential to advance scientific research and therapy development, study sponsors must embrace new paradigms to ensure accurate data capture and sustained patient engagement from remote locations.
Human-centric design is especially critical for DCTs because patients hold the primary responsibility for data capture and submission. Protocols must align with patients’ abilities and their lifestyles. To achieve this goal, sponsors must directly involve patients in the design phase as early as possible, and throughout the study as protocols evolve. Participant input and assessment is equally important after the study concludes to drive continuous improvement for future research.
The patient-centric focus must extend to the technology used to conduct DCTs. The devices and software deployed must meet patients where they are in terms of their geographic location, physical and cognitive limitations, and technology acumen. The technology must be easy to use, while still enabling researchers to collect significant and scientifically viable data. Further, to encourage engagement and retention, the technology has to provide an immediate and ongoing benefit to the user.
Increasingly, this translates to the need for a true consumer-level technology experience.
Tools of the Trade
eCOA/ePRO tools are essential to DCTs. These technologies and other clinical trial applications have proliferated in recent years. Like trial protocols themselves, however, most have been designed from the perspective of sponsors and investigators – not participants.
Many clinical trial applications today are built on the back of clinical data-based systems, such as electronic data capture systems. Primary users of these systems are clinicians and data specialists. Therefore, simply extending these foundations will not produce a patient-centric or patient-friendly platform. Applications intended for patients must be purpose-designed for them and not simply converted from legacy, data-centric systems.
Many smartphone-based instruments for clinical and real-world research continue to be text-based. For example, PROs migrated from paper onto PDAs, then more recently to smartphones, but most remain in the paper/text/content format and lack a user-friendly interface and experience. Today’s smartphone technology provides a fertile ground for new patient-centred ePRO innovation.
Interest in the need for patient-centric solutions is growing and new options are emerging. A recent study demonstrated that a novel data capture interface incorporated into an eCOA/ePRO app can offer a validated alternative to text-based, smartphone-based instruments for clinical, post-marketing, and real-world research. A study conducted by SAFIRA Clinical Research at Dublin City University showed equivalence (a high ICC) between the novel digital data capture interface and the standard Verbal Response Scale for capturing PRO data.
Delivering Immediate and Sustained Value to Participants
Sustained participant engagement is a perennial challenge for researchers. DCTs and the technology that supports them offer new promise to expand engagement, with the ability to effectively introduce behavioural psychology as a mechanism to personalise and optimise a participant’s trial experience.
Harnessing behavioural psychology concepts, such as gain or loss framed messaging delivered via digital technology, can ensure patients are encouraged to engage with the trial at key touch points, and drive realisation of value from their participation. For example, this can include message framing to encourage the right behaviours, such as attending the visits.
Harnessing it All Comes Together in a Decentralised, Virtual Study
Let’s return to the example of hypoglycaemia and how a decentralised, virtual study is helping researchers gain new insight into the impact of this frequent complication of Type 1 diabetes. The Hypo-RESOLVE project funded through the EU Innovative Medicines Initiative (IMI) launched Hypo-METRICS, a virtual study led by King’s College London to investigate the impact of hypoglycaemia on patients’ lives (2).
Historically, understanding the prevalence and effect of hypoglycaemia events (hypos) has been challenging due to the lack of proven, real-time, and easy-to-use tools to measure the day-to-day occurrence and impact of symptoms. Though diabetes studies often track hypo incidence, typical monitoring approaches gather patient-reported health (PRH) information retrospectively, which affects both data quantity and reliability.
The Hypo-METRICS study used Ecological Momentary Assessments (EMAs), which capture real-world data close to the time of an event. While EMAs can provide more accurate data for researchers, the need for frequent data capture can place a high burden on patients, potentially leading to lower levels of participation and higher levels of attrition. The Hypo-METRICS study team needed to ensure an easy and engaging EMA data capture experience for patients. The Hypo-METRICS team and patient advocates designed novel questionnaires in multiple languages, and delivered through an eCOA/ePRO platform, to evaluate various hypoglycaemia symptoms. The Hypo-METRICS app also tracks intensity levels of common hypo symptoms including sweating, heart palpitations, shaking, hunger, confusion, headache, movement, coordination, and speaking difficulties.
Patients recorded all hypos at or near the time of occurrence using the data tracking interface. Every day, patients completed three subjective EMA questionnaires and the EQ-5D-5L questionnaire. Each week, patients also completed the Patient-Reported Outcomes Measurement Information System (PROMIS) and the Work Productivity and Activity Impairment Questionnaire (WPAI). In addition, patients wore a blinded continuous glucose monitoring (CGM) device (the Freestyle Libre 2 provided by Abbott Diabetes) that continuously tracked their glucose ranges. Sleep data was collected using Fitbit Charge 4.
The virtual study represented the first-ever combination of PROs and CGM data at scale (250,000 patient-captured data points) and introduced a new methodology to assess the impact of hypos. PRH was higher than in previously reported studies of diabetes, which attests to the benefit of real-time reporting. In addition, linking subjective patient data captured via the app with CGM data yielded insight that can drive new discoveries about the relationship between CGM and PRH events. Further, most study participants had greater than 90% questionnaire compliance. Attrition was low, with only 1% of participants dropping out after the first week of the study.
What’s Next for DCTs?
Regulatory agencies and researchers alike are optimistic about the potential of DCTs to accelerate and expand participation in scientific study. As with any emerging scientific methodology, the industry will continue to learn, adapt, and evolve along the way to ensure the highest standards of patient safety, data security, and scientific integrity. At the second Decentralized Trials and Research Alliance (DTRA) in 2022, regulators from the US and Europe discussed the need for data consistency across platforms, a holistic view of the patient, and the need for robust communications plans and systems to maintain contact with patients, sites, and clinical trial managers.
All of these challenges are readily surmountable, and technology innovation – specifically solutions engineered around the patient experience – will once again lead us forward.
1. Burrows A, Report: Impacts of Decentralized Clinical Trials 2021, informaconnect, 2021
2. Søholm U et al, Investigating the day-to-day impact of hypoglycaemia in adults with type 1 or type 2 diabetes: design and validation protocol of the Hypo-METRICS application, BMJ Open, 1; 12(2), 2022