The 2024 DIA conference session on decentralized clinical trials (DCTs) brought together leading experts from various sectors to discuss the evolving landscape of clinical research. Chaired by Rasika Kalamegham, PhD, Head of U.S. Regulatory Policy at Genentech, the session featured insights from Jane Elizabeth Myles, MSc, Program Director at the Decentralized Trials and Research Alliance (DTRA); M. Khair ElZarrad, PhD, MPH, Director of the Office of Medical Policy at the FDA; and Dylan Bechtle, MS, Associate Director at Johnson & Johnson. The discussion highlighted the transformative potential of DCTs in making clinical research more patient-centric and efficient.
Redefining Decentralized Clinical Trials
Jane Myles emphasized that decentralized trials are not synonymous with fully remote studies. Instead, she advocates for using decentralized methods or elements that aim to reduce patient burden by allowing assessments outside traditional research sites. This approach aligns with the FDA’s draft guidance, which defines DCTs as decreasing patient burden by enabling some or all assessments to be conducted remotely. Myles elaborated on the importance of reducing patient burden, noting that traditional clinical trials often require patients to travel long distances to research sites, which can be particularly challenging for those with mobility issues or chronic illnesses.
By incorporating decentralized elements, such as home health visits or remote monitoring, trials can become more accessible and convenient for participants. This improves patient recruitment and retention and ensures a more diverse population can participate in clinical research. ElZarrad added that the FDA’s draft guidance clearly defines decentralized clinical trials, emphasizing that the goal is not to replace traditional trials but to enhance them with innovative methods. For example, remote monitoring technologies can collect real-time patient health data, reducing the need for frequent in-person visits and allowing for more timely interventions.
The Importance of Flexibility and Customization
Khair ElZarrad highlighted the need for flexibility in trial design, likening decentralized elements to Lego pieces that can be assembled in various ways to suit the specific needs of a trial. He explained that each clinical trial has unique patient populations, interventions, and logistical considerations. Therefore, it is essential to customize the trial design to fit these specific needs rather than adopting a one-size-fits-all approach. ElZarrad provided an example of a cancer trial where patients might need frequent imaging studies. In such cases, decentralized elements could include using local imaging centers instead of requiring patients to travel to a central research site.
The Role of Regulatory Guidance
The FDA’s draft guidance on decentralized clinical trials was a focal point of the discussion. ElZarrad explained that the guidance is part of a broader effort to integrate innovative clinical trial designs and technological advances into pharmaceutical development. He emphasized that the guidance is not intended to be a one-size-fits-all solution but a framework that can be adapted to different trial designs and contexts. ElZarrad highlighted several key aspects of the guidance, including the importance of data management and safety monitoring plans. He explained that these plans are essential for ensuring decentralized elements do not introduce additional risks to patients or data quality.
For example, a data management plan might outline how data collected through remote monitoring devices will be integrated with data from traditional site visits, ensuring that all data is accurate and reliable. The guidance also addresses using digital health technologies (DHTs) in decentralized trials. ElZarrad noted that DHTs, such as wearable devices and mobile health apps, can provide valuable real-time patient health and behavior data. However, it is crucial to ensure that these technologies are validated and that the data they collect is secure and reliable. The FDA’s DHT guidance provides detailed recommendations on evaluating and implementing these technologies in clinical trials.
Overcoming Industry Hesitation
One of the significant challenges in adopting decentralized clinical trials is the industry’s risk aversion, particularly concerning regulatory inspections. Bechtle noted that sponsors must demonstrate that DCT elements do not introduce additional risks to patients or data quality. He pointed to the FDA’s guidance on data management and safety monitoring plans as essential for ensuring that DCT methodologies are robust and reliable. Bechtle shared an example from Johnson & Johnson, where they implemented a decentralized element involving the direct shipment of investigational products to patients’ homes. This approach required careful planning and coordination to ensure the products were stored and handled correctly.
By developing a comprehensive data management and safety monitoring plan, the company demonstrated to regulators that the decentralized approach did not compromise patient safety or data integrity. ElZarrad emphasized that regulatory agencies are data consumers, not data generators. Therefore, sponsors are responsible for providing detailed information on how decentralized elements are implemented and how they impact the trial. He noted that the FDA’s draft guidance encourages sponsors to provide context and justification for using decentralized methods, helping regulators understand the rationale behind these approaches.
The Value of a Common Lexicon
The panelists agreed on the importance of having a common lexicon to facilitate better stakeholder communication. Myles mentioned that DTRA has been working on a glossary of terms related to decentralized methods, which they plan to offer to the NIH as part of an ongoing Request for Information (RFI). This effort ensures all stakeholders are on the same page when discussing decentralized clinical trials. Myles explained that the glossary includes definitions for various decentralized methods, such as remote monitoring, home health visits, and direct-to-patient shipments. By providing clear and consistent definitions, the glossary helps ensure that all stakeholders, including sponsors, regulators, and research sites, have a shared understanding of these terms.
ElZarrad noted that the FDA’s draft guidance also includes definitions for key terms related to decentralized clinical trials. He emphasized that a common lexicon is essential for effective communication and stakeholder collaboration. For example, when discussing a decentralized trial design, it is important that all parties understand what is meant by terms like remote monitoring or home health visits. Dylan Bechtle added that a common lexicon can help reduce confusion and miscommunication, mainly when working with multiple stakeholders. He shared an example from Johnson & Johnson, where the company used the DTRA glossary to ensure that all team members, including those from different departments and external partners, consistently understood the terms related to decentralized methods.
The Tubestop Diagram: A Practical Tool for Implementation
Jane Myles introduced the Tubestop diagram, a comprehensive tool developed by DTRA to guide stakeholders through the planning, execution, and closure of clinical trials. The diagram functions like a subway map, allowing users to dive into specific aspects of a trial and access relevant regulatory guidances and best practices. This tool aims to demystify the complexities of decentralized clinical trials and provide a practical roadmap for implementation. Myles explained that the Tubestop diagram was developed in response to the need for a sensible, user-friendly tool to help stakeholders navigate decentralized trials’ complexities.
The diagram is designed to be intuitive and easy to use, with each stop representing a different stage of the trial process. Users can click on a stop to access detailed information and resources related to that stage, including regulatory guidance, best practices, and case studies. For example, the planning stop includes resources on trial design, patient recruitment, and site selection. Users can access best practices for incorporating decentralized elements into the trial design and case studies from other trials that have successfully implemented these methods. The execution stop provides information on data collection, monitoring, and safety management, with links to relevant regulatory guidances and tools for ensuring data integrity and patient safety.
The Future of Clinical Trials
The session concluded with a discussion on the future of clinical trials, particularly the role of the FDA’s new Center for Excellence in Clinical Trial Innovation (C3TI). ElZarrad explained that the center aims to break down silos within the FDA and serve as a hub for knowledge sharing and collaboration. This initiative is expected to facilitate the adoption of innovative trial methodologies and improve clinical research’s overall efficiency and effectiveness. ElZarrad highlighted several key goals of the C3TI, including fostering collaboration among different FDA departments and providing a centralized resource for information on innovative trial methodologies.
He noted that the center will also focus on training and education, helping FDA staff stay current on the latest clinical trial design and technology developments. Dylan Bechtle emphasized the importance of generating evidence to support decentralized methods in clinical trials. He noted that sponsors often hesitate to adopt new methodologies due to concerns about regulatory acceptance and data quality. By providing a centralized resource for evidence and best practices, the C3TI can help address these concerns and encourage the adoption of innovative trial designs. Jane Myles added that the C3TI will facilitate collaboration between the FDA and external stakeholders, including sponsors, research sites, and patient groups.
Moe Alsumidaie is Chief Editor of The Clinical Trial Vanguard. Moe holds decades of experience in the clinical trials industry. Moe also serves as Head of Research at CliniBiz and Chief Data Scientist at Annex Clinical Corporation.
