In recent years we have witnessed a remarkable transformation in how clinical trials are designed and conducted. Specifically, traditional research paradigms, which typically have rigid structures and sequential phases, are giving way to more dynamic, patient-centric approaches. This shift was the focal point of a conference session chaired by N-of-1 Hub Director, Dr Suzanne McDonald, at the 2024 ARCS Annual Conference held in Sydney from 12th-14th June 2024 called ‘The Future of Medicine: The Confluence of Devices, Drugs and Data’.
ARCS is one of Australia's leading clinical trial conferences. The session entitled ‘On Revolutionising Clinical Trials: Innovation in Approval Processes and Trial Design’ included two presentations that outlined the benefits and challenges of specific innovative trial designs and approaches. In opening the session, Dr McDonald highlighted the movement towards flexible and efficient trial designs such as adaptive trials and platform trials, as well as the increased adoption of decentralised clinical trials and teletrials, driven by the COVID-19 pandemic and the need to include more diverse patient groups. These innovations not only expedite the development of therapeutic products and optimise resource utilisation, but also place patients at the heart of our research endeavours.
SKYHOOK: A High-Impact, Low-Burden Model for Initiating Rare Disease Trials
Dr Tanya Symons (T Symons Associates) delivered the first presentation in the session, introducing ‘SKYHOOK’, a high-impact, low-burden model for initiating rare disease trials initiated by the Australian Clinical Trials Alliance (ACTA). Dr Symons discussed the struggle to recruit participants in rare disease trials due to the limited patient population and explained how SKYHOOK can address this. SKYHOOK is a 'just-in-time' model (Wyatt & Volchenboum, 2024) that streamlines trial setup, ensuring timely access to cutting-edge treatments for people with rare disease. By establishing a consortium of clinicians, researchers, and key stakeholders, SKYHOOK aims to secure 'in-principle' approval for swift trial initiation at new patient care sites, thus improving trial accessibility and efficiency. After this presentation, Tyron Johnson, Senior Clinical Research Lead in Oncology from Eli Lilly Australia, shared his views on whether industry sponsors should support the implementation of SKYHOOK and what he would like to see happen after the pilot is completed. He was overwhelmingly positive about his experience of SKYHOOK and advocated for the broader adoption of SKYHOOK beyond the rare disease space.
Pooled N of 1 Trials: Providing Innovation in Protocol and Design
In the second presentation, Dr Suzanne McDonald (N-of-1 Hub) focused on pooled N of 1 trials. She started by introducing N of 1 trials as individualised randomised controlled trials, where patients serve as their own control to provide detailed insights into individual treatment responses. She explained that a series of N of 1 trials can be statistically pooled using Bayesian multilevel models, allowing estimation of individual and population-based treatment effects. Individual and pooled N of 1 trials are recognised in guidelines from major regulatory bodies across the globe, including the European Medicines Agency, the Food and Drug Administration, and Therapeutic Goods Administration. One of the main advantages of pooled N of 1 trials is that they require fewer participants than traditional trial designs to achieve the same statistical power (Blackston et al, 2019), reducing time, cost, and recruitment challenges. This is particularly useful for studying populations where participants are hard to recruit or retain. Dr McDonald encouraged attendees to join the International Collaborative Network for N-of-1 Trials and Single-Case Designs, a global network that aims to further the science and application of N of 1 trials and single-case designs (Nikles et al., 2021).
Looking to the Future of Clinical Trials
The discussions in this conference session reinforced the critical role of innovative trial designs and approaches in the future of clinical research. As clinical trials continue to evolve, the integration of dynamic, patient-centred designs and approaches will be essential in overcoming the barriers/shortcomings of standard clinical trials, optimising resources, and ultimately enhancing patient outcomes.
N-of-1 Hub is a consulting company that specialises in designing, conducting and analysing personalised clinical studies using single-case designs. N-of-1 Hub provides consulting and collaborative services to companies, clinicians, researchers, and healthcare consumers who wish to conduct personalised clinical studies using single-case designs. N-of-1 Hub also offers data management and analysis services and customised workshops and courses.
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References:
Blackston, J. W., Chapple, A. G., McGree, J. M., McDonald, S., & Nikles, J. (2019). Comparison of aggregated N-of-1 trials with parallel and crossover randomized controlled trials using simulation studies. Healthcare, 7, 137. https://doi.org/10.3390/healthcare7040137
Nikles, J., Onghena, P., Vlaeyen, J. W., Wicksell, R. K., Simons, L. E., McGree, J. M., & McDonald, S. (2021). Establishment of an international collaborative network for N-of-1 trials and single-case designs. Contemporary Clinical Trials Communications, 23, 100826. https://www.sciencedirect.com/science/article/pii/S2451865421001277
Wyatt, K. D., & Volchenboum, S. L. (2024). Targeted Enrollment in Pediatric Oncology Trials: A Vision for Just-in-Time Matching. JCO Oncology Practice, 20(5), 603-606. https://doi.org/10.1200/OP.23.00826