New Insights: International Clinical Trial Regulatory Innovation

At the recent Duke-Margolis Institute for Health Policy conference, regulatory experts worldwide gathered to discuss advancements and collaborative strategies in international clinical trial designs and regulatory innovation. Yuki Ando, Principal Senior Scientist for Biostatistics at Japan’s Pharmaceuticals and Medical Devices Agency (PMDA), Sarem Sarem, Sr. Pharmacometrics Assessor at Health Canada, Andrew Thomson, Statistician at the European Medicines Agency (EMA), and M. Khair ElZarrad, Director, Office of Medical Policy, Center for Drug Evaluation and Research (CDER) at U.S. Food and Drug Administration (FDA), discussed a unified call for enhanced cooperation and adaptive regulatory environments to foster innovation in clinical trials.

Japan’s Approach

Yuki Ando of Japan’s PMDA highlighted the significant strides to enhance clinical trial designs, mainly focusing on integrating multiregional clinical trials. These trials, which are inherently more complex due to their global nature, are instrumental in expediting data collection and ensuring its applicability across different populations. By promoting an innovative regulatory approach that encourages multiregional trials, PMDA supports global collaboration and facilitates quicker access to new therapies.

In addition to adopting more inclusive trial designs, PMDA is pioneering diverse data sources in drug application processes, including real-world evidence and data from electronic health records. Ando emphasized the agency’s commitment to creating guidelines that mirror the dynamic interplay between regulatory bodies and the pharmaceutical industry. Engaging with industry players ensures that the resulting regulations are practical, address research and development hurdles, and reflect the evolving landscape of global drug development.

Canada’s Perspective

Sarem Sarem from Health Canada delved into the transformative potential of modeling and simulation for international clinical trial design and analysis. He articulated the substantial benefits these computational tools bring to the pharmaceutical landscape, notably in optimizing trial designs and enhancing the robustness of analytical methods. Sarem pinpointed the industry’s key challenge: the variability and inconsistency in how various regulatory bodies perceive and accept modeling and simulation results. This inconsistency can lead to hesitancy and underutilization of these advanced methodologies, potentially stifling innovation.

Sarem emphasized the development of a risk-based assessment framework as a solution to this issue. Such a framework would evaluate modeling and simulation strategies based on the risks they present to the trial’s integrity and the validity of its outcomes. By doing so, Health Canada aims to encourage more widespread and efficient use of these tools, fostering an environment where clinical trials can be conducted more swiftly and with greater precision. The goal is to shift away from a one-size-fits-all approach to a more nuanced model that considers the unique aspects of each trial, thereby promoting innovation while ensuring patient safety and data quality and enabling a more harmonious and progressive approach to drug development.

EMA’s Take

Andrew Thomson of the EMA presented a compelling narrative on incorporating real-world evidence (RWE) into the regulatory aspect of clinical trials. RWE is rapidly gaining recognition for its potential to augment clinical research and provide a more comprehensive view of patient outcomes. Thomson pointed out that integrating RWE requires a significant transformation within the regulatory ecosystem, particularly in the roles of inspectors and assessors. Traditionally focused on the integrity of international clinical trial data, these professionals are now navigating the complexities of assessing evidence from broader, less structured data pools such as electronic health records and patient registries.

Thomson stressed the critical nature of change management in the face of these innovations, acknowledging the need for updated skill sets and a reshaping of regulatory guidelines to embrace RWE’s full potential. He highlighted the importance of training and the development of new competencies as pivotal in ensuring that inspectors and assessors can confidently evaluate the validity and applicability of RWE. This shift demands reevaluating existing protocols and opens doors to a more agile and responsive regulatory approach, ultimately benefiting patient care by leveraging a richer, more real-world-oriented evidence base to inform clinical and regulatory decisions.

FDA’s Outlook

M. Khair ElZarrad from the FDA outlined the FDA’s initiatives to modernize regulatory frameworks in response to the burgeoning pace of innovation in the clinical trials sphere. ElZarrad emphasized the need for a globally consistent approach to clinical trials, reflecting the fast pace of innovation and the importance of incorporating global data sources and technological tools, and that the processes governing the development of regulatory guidelines must evolve in tandem. The FDA is advocating for a transformation beyond mere updates to existing guidelines; it is championing a reimagining of the mechanisms that underlie guideline creation, aiming for seamless integration of advancements in international clinical trial methodologies.

ElZarrad illuminated the agency’s vision for a globally harmonized regulatory landscape that can efficiently manage and harness the power of worldwide data and state-of-the-art technology. This vision encompasses a shift towards regulations uniformly accepted across borders and agile enough to adapt to the modern research environment’s swift technological changes. By focusing on creating such a universally consistent framework, the FDA is positioning itself as a leader in fostering a collaborative international approach. This approach aims to ensure innovative therapies can be developed and delivered to patients with efficiency and safety at the forefront, leveraging global innovation while maintaining rigorous data integrity and patient protection standards.

A Call For Global Regulatory Harmonization

The session emphasized the need for collaboration among stakeholders in clinical trials to drive genuine innovation. By dismantling silos and fostering interdisciplinary collaboration, regulatory bodies, pharmaceutical companies, healthcare providers, and patient advocacy groups can share insights and enhance trial designs, accelerating clinical development and improving patient outcomes.

Additionally, establishing adaptive regulatory environments is crucial for accommodating emerging innovations like digital twin technology, decentralized trials, and digital tools. Flexible regulatory frameworks ensure that new methodologies are integrated efficiently and evaluated rigorously, promoting safe and effective clinical practices. This collaborative and adaptive approach is vital for advancing clinical trials and benefiting patients globally.