By Exploristics CEO, Aiden Flynn
Pandemic successes like the RECOVERY trial have provided the pharmaceutical industry with a glimpse of how innovative trial design could shake up historic approaches to clinical development to drive greater efficiency. They have reignited interest from government, healthcare providers, regulators and industry alike in improving development outcomes with innovative and complex clinical trial designs. In recent years, the FDA and EMA have both recognised their potential, outlining their benefits in the FDA new areas of focus and the EMA’s strategic reflection to 2025. Industry has also been considering more closely how to unlock their value more widely.
Reviewing the Clinical Trials Landscape
In 2020, the EFPIA clinical trial design taskforce reviewed the clinical trial design landscape, focusing on enrichment designs, adaptive designs, master protocols and the use of historical controls https://www.efpia.eu/media/547507/efpia-position-paper-innovation-in-clinical-trial-design-white-paper.pdf. Their aim was to increase ‘awareness, understanding and acceptance’ of innovative trial design amongst stakeholders. They found that if properly pre-planned, these approaches could help improve the success of clinical trials. However, while their uptake was growing, wider implementation was still quite limited despite some solutions like adaptive designs being available for over a decade.
Identifying Obstacles
In their review of the clinical trials landscape, the EFPIA taskforce identified some of the key obstacles to the wider uptake of innovative trial designs. These included:
- a lack of knowledge on design strategies and methods
- a lack of validated software
- uncertainty around the acceptance by regulators and HTA agencies of the evidence generated
- the logistics of conducting more complex designs
- limited expertise in designing and implementing innovative trials
Breaking Barriers
Since then, efforts have been made to move the dial on such barriers by groups like the Drug Information Association (DIA) Adaptive Design Scientific Working Group and PSI special interest groups who offer publications and courses to improve outreach and understanding across disciplines, industry, academia and regions. There are now also more study design software solutions and greater regulatory guidance. Nevertheless, despite the enormous potential innovative trial designs offer in transforming the speed and efficiency of evidence generation in clinical development there is a continued slow burn on uptake. So, what further barrier remains?
A Cultural Shift
Continued hesitancy around the use of innovative trial designs may indicate the need for a cultural as well as a practical shift in how clinical trials are designed. Changing the culture may involve:
- Bringing the design and data experts into the room earlier. The increased complexity of these designs requires specialist expertise to support their design, execution and analysis. This may go beyond the direct expertise of the clinical research teams who usually design and conduct the trials.
- Hitting the pause button on the need for speed. Many development projects are under pressure to hit the ground running, with research teams looking to have everything in place for key milestones like first-subject-first-visit (FSFV).
The greater efficiency and flexibility offered by innovative but more complex clinical trial designs demands earlier involvement by a more diverse, data savvy multidisciplinary team, including statisticians. It is still the case that statistical input into the design of studies is often not sought until most of the key design decisions have been made. This is not working well for simple study designs and is completely unfeasible for more complex ones.
Considering complex designs also requires a little more time at the planning stage which may appear to be slowing up the inexorable rush towards key milestones. However, this small investment at the start can reap dividends in terms of timelines, costs and patient burden later. Ultimately, nothing is more time-wasting than a study failing due to inappropriate design.
A Paradigm Shift
Embracing more innovative trial designs has already been shown to deliver faster, more effective development during the pandemic. Widening their uptake with a more multidisciplinary approach to design offers an opportunity to shift the current development paradigm which has accepted high failure rates and costs for too many years. However, this will require changing the traditional development culture to bring statisticians into the heart of clinical trial design decisions. Only with earlier statistical engagement can we hope to improve development outcomes to deliver better ROI on R&D. More importantly, it puts the needs of patients first ensuring their valuable involvement has not been wasted.
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