In the last 18 months, clinical research has experienced momentous change. We have been challenged by the reality of research delays and halted programs—while simultaneously rising to meet the needs of patients—to maintain trial continuity and apply science to overcome global health problems.
As an industry, we should be proud. Not just that we’ve navigated this research paradox and its difficulties, but that ingenuity is now realizing important benefits for future trial design and for patients. Yet, there is more to be done. We’re now at an important inflection point in the industry’s approach to trial design and we must ask ourselves: How do we take forward everything we have learned and embrace this important step change while maintaining the highest quality standards?
At the crossroads of clinical research
While the pandemic forced the rapid introduction of new research and operational activities, clinical development practices have been evolving for some time. The traditional research model was already challenged by an increasingly complex environment, with groundbreaking science fueling next-generation modalities and shifting cultural approaches. This movement had catalyzed new developments in many areas, including trial design, peripheral technologies, data storage and analysis, and genetic stratification in cohort selection.
We were already on the road to change, but the pandemic has been a major accelerant. What we’ve been through is a little like the automotive industry being given a year to make every car on the planet electric. I use this light-hearted example to emphasize the magnitude of change, while maintaining the highest standards of quality.
A step change with quality at its core
Reflecting on how far we’ve come since early 2020, it’s remarkable to think we have successfully transformed our trial approach and initiated ‘pandemic proof’ operating models while still delivering innovation.
Tools and technologies such as virtual site initiation visits and direct-to-patient drug shipments offer more flexibility for patients and reprioritized procedures based on study objectives. The impact of these changes will be positive and long-lasting, reducing the overall burden on patients and accelerating clinical development. While the physical reality of trials has dramatically altered, our quality objectives have stayed constant: to protect patients and data integrity.
A ‘critical to quality checklist’ for trial design
Ensuring quality in clinical trial design—versus the traditional ‘quality by quality control’ approach—is critical to realizing the potential of a new, modernized approach and a standard of practice that protects study participants and delivers reliable, meaningful data for patients and regulatory decision makers.
The International Council for Harmonization (ICH) E8, General Considerations for Clinical Studies section of the Good Clinical Practice Guidelines, recommends a proactive approach to identify the Critical to Quality Factors in a study—those elements that are fundamental to the safety and protection of patients, data quality, and decisions made based on study results.
If we look at our learnings from the pandemic and steps needed to drive positive change forward, we can see how the recommended approaches might help.
The pace at which decentralized clinical trials have been implemented has focused our minds on what was really necessary to ensure a safe and successful transition from an ‘in-person’ to ‘virtual’ clinical trial experience. Simplifying or eliminating unnecessary procedures can help to prioritize the outcomes that are most meaningful to patients, as well as safety and ethical conduct.
Gaining perspectives from a broad range of stakeholders including patients, physicians, and clinical investigators can also help identify important insights on study design. Early consultation with patients can positively shape and embed quality in a trial and improve overall experience, empowering patients to take a more active role and potentially leading to greater adherence and retention.
Reviewing Critical to Quality Factors on an ongoing basis, and proactively employing a risk-based management approach, will enable us to continue to work at the accelerated pace while maintaining important quality principles. By identifying potential risks as part of protocol design, we ensure efficiency and speed in our development process, increase confidence in data captured, and mitigate errors, which will reduce delay in delivering value for patients.
Together, these approaches can support careful planning and quality in trial design, ensuring a targeted focus on objectives and removing complexity and unnecessary burdens.
Quality as a habit
It is undeniable that the adversity of the pandemic has left its legacy on clinical trials. Fundamentally, it has accelerated patient centricity, and reduced the burden on individuals and caregivers, allowing for greater patient engagement and the potential for stronger data packages.
As the guidelines so clearly state, creating the right culture is also critical. At Astellas, we continue to nurture a ‘culture of quality’ across our organizations—one that empowers individuals, encourages critical thinking and values proactive, as well as open dialogue to help identify the factors that are truly essential to trial quality and outcomes. In this way, we strive to elevate our trial delivery with patient safety and data integrity as the foundation. In fact, it is this cultural grounding that carried our organization during the early, uncertain days of the pandemic, enabling a strong foundation for quality and business continuity.
Quality and excellence are the foundations of our work in healthcare. It is inherent to both the efficacy and safety of the treatments we develop for patients. As an industry, we must maintain a constant state of learning and improvement, embedding quality-by-design principles at the core of our work. This will help to realize the true opportunity of an enlightened research model and allow us to do the very best by the patients we serve.
Bernhardt G. Zeiher, M.D., F.C.C.P., F.A.C.P.
Chief Medical Officer, Astellas Pharma Inc.