Industry and FDA Insights on Clinical Trial Regulatory Change

At the Duke-Margolis Institute for Health Policy conference, industry and government leaders delved into the future of clinical trials and regulatory change, addressing critical issues and innovative approaches to modernizing the FDA’s regulatory infrastructure. Monica Bertagnolli, Director of the NIH, discussed integrating clinical trials with community healthcare needs, while Ned Braunstein, EVP of Regulatory Affairs and Global Patient Safety at Regeneron, emphasized balancing innovation with FDA regulatory standards. Robert Metcalf, Clinical Design Delivery and Analytics at Eli Lilly, highlighted the need for regulatory change to support modernized trials, and Esther Krofah, Executive Vice President, Milken Institute Health, focused on increasing trial access and representation for diverse populations. Janet Woodcock, formerly Director of CDER at the FDA, advocated a ‘quality by design’ approach to make clinical trials more relevant and inclusive.

The NIH Vision: Community-Centric Clinical Trials

In her insightful discourse, Monica Bertagnolli conveyed the critical challenges our healthcare system faces, particularly emphasizing the concerning trend of declining life expectancy. This, she pointed out, was primarily attributable to what she termed ‘diseases of despair,’ including mental health struggles, substance abuse issues, and insufficient progress in tackling cardiometabolic conditions. Bertagnolli articulated the NIH’s concerted response to these challenges by forming a wide-ranging clinical trials network, designed not merely as a stand-alone project but as a multifaceted collaborative venture that spans the entirety of the NIH’s various institutes and centers.

Reflecting a shift towards inclusivity and practicality in research, Bertagnolli emphasized that clinical trials would be elective for sites, allowing them to choose studies most relevant to their communities’ health needs and their own operational capabilities. According to Bertagnolli, this strategic move aims to equip and involve primary care practitioners directly in the research process, thus closing the gap between healthcare provision and clinical research. “We intend for these sites, joined as a network, to be able to use a common clinical trials mechanism… to be offered as big a list as we can make it of research opportunities, anything ranging from participation in a really high quality registry to participation in a prospective randomized registration trial,” said Bertagnolli.

Regeneron’s Feedback on Regulatory Transformation

Ned Braunstein from Regeneron emphasized the crucial role of scientific innovation in clinical trials. He advocated for methods that streamline the translation of preclinical discoveries into clinical settings, potentially reducing the need for comprehensive endpoint data. He argued, however, for a balance between innovation and regulation, noting the distinct challenges pertaining to personalities within regulatory bodies that come with varying degrees of risk tolerance. “When we work with regulators… we’re dealing with people… each of the divisions have their own personalities and they have their own level of risk tolerance,” said Braunstein. Highlighting the need for change management, Braunstein called for a regulatory culture that promotes innovation while adhering to strict compliance standards. “One of the things that I would urge you to treat… is change management,” added Braunstein.

Braunstein also acknowledged the necessity for clarity in regulatory expectations and the preparation required by biopharmaceutical enterprises to meet them, especially during inspections. Braunstein said, “To have an inspector come in, and if we don’t know what we’re going to be inspected on… it’s very hard for us to know (the inspector’s expectations)… and that we’re adequately prepared.” This bolsters his call for transparent communication and robust internal support systems to ensure research paradigms can be adapted without sacrificing the integrity of clinical research.

Lilly’s Approach to Regulatory Modernization

Robert Metcalf from Eli Lilly provided an insightful overview of the evolution of clinical research, recognizing the efforts of the FDA in fostering innovation through updated guidance documents. However, Metcalf identified a critical gap between the pace of regulatory change and the rapid advancements in clinical research methodologies in the industry. He pointed out that many regulations were designed for an outdated model of clinical trials—predominantly single-site and paper-based. “Areas like modernizing how we think about investigator oversight… these regulations were developed generally when we had single centers with single investigators and very much in the paper-based environment.” According to Metcalf, this model is increasingly at odds with the current trend towards decentralized trials that leverage technology to engage participants directly in their communities, thereby broadening the scope and diversity of clinical research.

Metcalf advocated employing innovative trial designs, like Bayesian and adaptive designs, to make clinical research more efficient and effective. Metcalf highlighted pediatric research as a field that stands to benefit significantly from these innovative methodologies, given its unique challenges around participant safety and the need for robust evidence. By adopting these advanced trial designs systematically, Metcalf suggested that the clinical research community could better address the complex needs of diverse patient populations while ensuring rigorous scientific data collection.

Equity in Trial Access and Representation

Esther Krofah highlighted the glaring disparities in clinical trial access, an issue that the COVID-19 pandemic presented. She pointed out that while academic medical centers in urban areas were quick to enroll patients for COVID-19 trials, rural and minority communities were left behind due to a lack of research infrastructure. This situation emphasizes access inequalities and the opportunity disparities for these communities to benefit from the latest medical advancements. To address this, Krofah advocated for creating a diverse and extensive network of trial sites that reflects the demographic composition of the entire United States, with each site focusing on conditions most prevalent in their respective communities.

Further elaborating on the need for systemic change, Krofah emphasized the importance of coordination and a shared vision among various organizations involved in clinical research. She argued that building a cohesive network that can address systemic trust issues and improve engagement in clinical trials, particularly among racial and ethnic minorities, is crucial. Krofah believes it is possible to overcome historical barriers to trial participation by promoting collaboration and fostering a united approach.

FDA’s Emphasis on Evidence-Based Practice

Janet Woodcock provided an insightful critique of the current state of clinical trials within the healthcare landscape, emphasizing the essential role of evidence-based research in improving patient care. She pointed out a significant issue: the medical community has historically overlooked clinical trials, often perceived as less critical than basic scientific research. According to Woodcock, this perspective detracts from clinical trials’ potential to offer transformative insights into patient treatment options and calls for a shift in how clinical research is valued and integrated into the healthcare system.

Woodcock then discussed adopting the ‘quality by design’ (QbD) approach to enhance the efficiency and applicability of clinical trials. This methodology focuses on creating trials to generate data that meets specific needs—be it for FDA regulatory approval or direct clinical application. Moreover, she stressed the importance of inclusivity in research, advocating for the participation of diverse demographics to ensure the findings are broadly applicable and to minimize translational issues. By emphasizing diversity and intentional design in clinical trials, Woodcock aims to build a stronger foundation of trust in research findings across different communities, ultimately fostering a more inclusive and impactful research environment.

Summary

At the Duke-Margolis Institute for Health Policy conference, experts discussed the future of clinical trial regulatory change, emphasizing the need for their integration with community healthcare and addressing the balance between innovation and regulation. The discussions highlighted the importance of modernizing FDA regulatory frameworks to accommodate decentralized, technology-driven trials and ensuring equity in trial access across diverse populations. Advocacy for innovative trial designs and a ‘quality by design’ approach was strong, aiming to make clinical research more efficient, effective, and inclusive. The overarching theme was the urgent need for adaptable, equitable clinical research methodologies to align with contemporary healthcare and research challenges.