Embracing Hybrid Trial Design — How, When, & Why To Use It
A conversation with Lewis Millen, Global Clinical Sciences & Operations Innovation Lead, UCB
Sift through any conference program, scroll through your LinkedIn feed, or just ask your colleagues — there are any number of ways to talk about clinical trials that don’t conform to the traditional on-site trial design.
They go by many names: decentralized clinical trials (likely the most commonly mentioned and the most polarizing), remote trials, virtual trials, hybrid trials, and more. And just as varied as the names are the ways in which they are implemented.
Here, UCB’s Global Clinical Sciences & Operations Innovation Lead Lewis Millen talks about UCB’s approach to it all, including why it’s opting for hybrid trial design, how and when it chooses to do so, and why it’s beneficial to both the sponsor and the patient.
We hear all the time about remote, virtual, and decentralized clinical trials, with each term used interchangeably but often defined differently depending on who you ask. How, then, do you define hybrid clinical trials, and how are they executed?
Millen: Hybrid clinical trials refer to a type of clinical trial that combines elements of both traditional site-based trials and remote activity. In hybrid trials, some study activities and potentially whole study visits are conducted at physical sites, such as hospitals or research centers, while others are performed remotely, utilizing digital tools and technologies as well as community healthcare.
The COVID-19 pandemic accelerated the adoption of decentralized clinical trial approaches, highlighting the importance of remote data collection and reducing the requirement for in-person visits. There are now many new methods of remote data collection, symptom reporting through mobile apps or electronic diaries, collecting patient-reported outcomes, and virtual visits.
Hybrid trials may also incorporate the use of wearable devices, such as activity trackers or biosensors, to collect continuous or real-time data remotely. These devices can monitor parameters like heart rate, sleep patterns, or physical activity levels, providing researchers with objective measurements in real-life settings.
By incorporating these decentralized elements into the clinical trial, we can combine the convenience of remote and virtual options with the need for closer monitoring at certain stages. This hybrid approach ultimately optimizes the trial experience and results for both patients and researchers.
Hybrid clinical trials allow some trial activities to be conducted in the clinic and some to be done in the home (or other non-clinical setting). How do you identify which activities can be successfully implemented in one setting versus another?
Identifying which activities can be successfully implemented in a clinical setting versus a non-clinical setting, such as the home, requires careful consideration and evaluation. First and foremost, we need to ensure the safety of the participants and the reliability of the data we collect, so optionality will never come at the expense of the welfare of patients or the reliability of the results.
Before we make decisions regarding a trial’s suitability for being conducted in a hybrid manner, we first look at the disease and its impact on patients and their families and caregivers to understand the opportunities and challenges decentralized clinical trial methodology and approaches might bring. We consider factors such as the potential impact on participant safety, data quality, patient burden, and study outcomes. Activities with higher risks or complexities may be better managed in a clinical setting with trained personnel, while low-risk activities may be suitable for non-clinical settings.
The nature of the activity and the requirements of a trial must also be taken into consideration. Activities that involve direct physical examinations, invasive procedures, or technology only available in a hospital are better suited for a clinical setting where healthcare professionals can ensure proper execution and patient safety. Conversely, activities that involve patient-reported outcomes, symptom reporting, or data collection through wearable devices can be more feasible to conduct remotely with negligible impact on data collection efficiency.
How does a trial’s therapy affect the decision to design a hybrid trial? And are there indications that are a better fit for a hybrid trial than others?
The nature of a trial's therapy plays a significant role in determining whether a hybrid trial design is suitable. Different therapies have unique characteristics that may influence the decision to adopt a hybrid trial approach, and different indications, too, have different considerations. The appropriateness of a therapy for a hybrid trial depends on various factors, such as the mode of administration, monitoring requirements, and disease characteristics.
Therapies that can be self-administered by participants or easily administered outside of a clinical setting are generally well-suited for hybrid trials. For instance, oral medications, subcutaneous injections, or therapies delivered through wearable devices are more amenable to remote or non-clinical settings.
The frequency and type of monitoring needed for the therapy are crucial considerations. If the therapy requires frequent monitoring, such as laboratory tests, specialized imaging, or intensive vital sign measurements, it may pose challenges for remote implementation. Hybrid trials are more suitable when monitoring can be conducted remotely or when the therapy requires less intensive monitoring.
Disease characteristics can affect the suitability of a hybrid approach. Conditions that require frequent patient-reported outcomes, symptom assessments, or quality of life measurements are well-suited for remote data collection in a hybrid trial. Additionally, chronic diseases with stable patient populations may be more amenable to hybrid trial designs, as they often involve long-term treatment and monitoring.
We must also assess the characteristics of the patient population, including geographic distribution and accessibility to trial sites. If the patient population is widely dispersed or faces significant barriers to participation, a hybrid model may offer increased convenience and access.
Although there are therapies and indications that generally coincide favorably with hybrid trials, it is crucial to assess each trial individually. A comprehensive assessment of the therapy, patient population, safety considerations, and logistical feasibility is necessary to determine whether a hybrid trial design is appropriate.
Hybrid trials inherently offer more flexibility than traditional trial models. Why is flexibility — in time and location — important to the patient experience?
Many of the patients that UCB serves have complex conditions and our aim is to make clinical trial participation as easy as possible, enabling participants to continue with their day-to-day lives with minimal disruption. By combining human-centered design, which considers not only the patient but the family and caregiver, with innovative technologies, we seek to increase flexibility and optionality. When patients need more flexibility due to the demands of a patient’s job, family commitments, and lifestyle, we endeavor to offer a home option.
Some study visits or consultations may be conducted virtually, using telemedicine or video conferencing platforms. These virtual visits allow for remote interactions between participants and healthcare providers, reducing the need for travel and enabling greater convenience.
To make our solutions relevant to the individual needs of each patient, it is essential to ensure that clinical trials are inclusive of the diverse communities we serve and address a wide range of unique situations experienced by each patient. That's why UCB is committed to incorporating options at every stage of drug development and treatment. By providing increased choices, we can broaden the participation of patients from diverse communities, various age groups, and even remote locations throughout the clinical trial process. This approach aims to empower a greater number of people to take part in trials and, therefore, allow the diversity of the communities that we serve to be reflected in the solutions that we develop.
Now that we understand patient benefits, what are the upsides for the sponsor company, vendors, and sites? And what are some of the challenges for each?
The increased communication and engagement with participants through digital means that a hybrid approach offers not only more convenience for patients, but it also can facilitate participant retention, adherence to study protocols, and enable timely exchange of information. These elements mean more data and potentially more meaningful data can be collected by the researchers and, therefore, lead to a more rigorous trial for the sponsor company and easier trial management by vendors.
By incorporating remote data collection and virtual visits, we can minimize the need for physical infrastructure, free up site availability for more trials, and reduce site overhead costs. Additionally, the ability to collect real-time data remotely can accelerate data availability and analysis, leading to faster trial completion.
Since a hybrid model relies so heavily on digital communication and data collection, one challenge is to implement and maintain a robust technology infrastructure, without losing a “high touch” approach that centers on human interaction. Emerging technology requires reliable internet connectivity, secure data storage, and user-friendly interfaces across different devices and platforms. This data must be stored in full compliance with data protection regulations.
With innovation, some challenges emerge only when planning and implementing for the first time. This is particularly relevant with novel solutions and vendors. There is a real need for enhanced communication channels and a continuous learning loop.
How does clinical trial technology play a role in hybrid trials? Where do you see gaps that technology can assist or fix? Where do you see evidence that technology is not yet mature enough?
Innovative technological solutions are at the center of the expansion of trials from the clinic into the home and placing patients’ needs at the heart of drug discovery to ensure that UCB solutions reach all communities and serve diverse human needs.
To that end, we are leveraging innovative technology to pilot and deploy remote patient-centric sampling and data capture solutions, such as PK blood sampling and non-invasive skin biopsies and imaging. We are continually looking to expand what is possible in the home. However, there will always be some tests that need to be performed in a clinical setting, such as invasive biopsies, which is why a hybrid clinical trial model takes the best of both the remote and clinical approaches.
In addition to the at-home testing solutions, UCB is working to deliver scalable digital solutions for clinical trials. We are adopting ePRO and eConsent to provide a patient-centric digital experience to study participants and will actively influence the strategic direction of these and other applications based on learnings.
In addition to product development, the partnership will address the regulatory landscape, focusing on advancing the adoption of these digital solutions. This long-term collaboration will involve the development of a collaborative strategic road map, ensuring the delivery of current and future products from the same vendor. The ultimate goal is to improve the speed and reduce costs associated with conducting clinical trials.
How prevalent are hybrid trials, and how do you see their presence and efficacy evolving over the coming years?
Hybrid trials have been gaining momentum in recent years, driven by advancements in digital technologies and decentralized trial services, increased focus on patient centricity, and the need for more flexible and efficient clinical trial models. Currently, At UCB, approximately 46% of eligible studies have implemented DCT or remote components.1
Looking ahead, I expect that hybrid trials will continue to grow in prevalence and evolve in their design and execution. It is difficult to say exactly where this will take us, but technological advancements will continue to drive innovation in what types of data can be collected remotely. Currently, we are leveraging cutting-edge technology to aid in patient monitoring and sample collection. As technology becomes more advanced, we may be able to conduct more and more complex tests from the comfort of our own homes.
Hybrid trials have the potential to generate real-world evidence (RWE) by capturing data in more naturalistic settings. RWE can complement traditional trial data by providing insights into the long-term effectiveness and safety of interventions in real-world patient populations. This can further support regulatory decision-making and post-market surveillance.
Overall, given the benefits they offer and the supportive trends in the clinical research landscape, it is anticipated that hybrid trials will become increasingly prevalent and play a significant role in advancing clinical research in the coming years.
Resources:
- Diversity in Clinical Trials: UCB Strategy, Nov 2022 (accessed 5th June) UCB_White_Paper_Diversity_in_Clinical_trials_2.0.pdf
About The Expert:
Lewis Millen has been the global clinical sciences & operations innovation lead at UCB for three years. He has more than 20 years’ experience in clinical research, in both early and late-stage medicines development, in pharma, biotech, and CROs. He has held a variety of roles in clinical science and operations across Phases 1 to 4, from CRA to study manager to clinical program lead. He is passionate about patient-centered clinical development, decentralized clinical trials, patient engagement, and increased recruitment and retention in clinical trials.