Decentralization - The Future of Clinical Trials

Introduction:

Decentralized clinical trials (DCTs) leads with a premise to leverage technology to transform the traditional clinical trials model. Incorporating digital tools, telemedicine, and real-world data, DCTs enhance flexibility, accessibility, and participant-centricity. Such a promising alternative addresses inefficiencies, high costs, and limited diversity, revolutionizing the landscape of medical research.

Traditional clinical trials have long served as the cornerstone of medical research, providing essential evidence for evaluating the safety and efficacy of new interventions. However, these trials often encounter significant challenges, including inefficiencies, high costs, logistical complexities, and limited participant diversity. Post the COVID-19 pandemic era, a groundbreaking approach called decentralized clinical trials (DCTs) has emerged as the new normal, harnessing technological advancements to revolutionize the landscape of medical research. This article explores the principles, key components, benefits, challenges, and future implications of decentralized clinical trials, highlighting their potential to accelerate the development of new treatments and improve patient outcomes.

Principles of Decentralized Clinical Trials

Decentralized clinical trials reimagine the traditional trial model by shifting from a centralized approach to a distributed one. They prioritize patient-centricity, accessibility, and flexibility, utilizing remote technologies and digital platforms to enable data collection, participant engagement, and real-world evidence integration. The principles of decentralized clinical trials emphasize the importance of designing studies that leverage these advancements to enhance efficiency, inclusivity, and scientific rigor while maintaining regulatory compliance and ethical standards.

Components of Decentralized Clinical Trials1

Decentralized clinical trials rely on several key components to redefine the trial process:

Digital tools and platforms: Remote data collection and monitoring technologies, such as electronic patient-reported outcomes (ePRO) systems and mobile health applications, enable participants to contribute data from the comfort of their homes, reducing the need for frequent in-person visits.

Wearable devices and sensors: Devices like smartwatches, biosensors, and implantable technologies provide real-time health monitoring, capturing objective data, ensuring continuous data capture and enhancing participant safety.

Telemedicine and virtual visits: Telemedicine facilitates remote participant engagement through virtual visits, allowing consultations, assessments, and follow-ups without physical travel. Telehealth platforms and video conferencing enable remote interactions between participants and healthcare professionals, facilitating virtual visits, consultations, and remote assessments. This enhances convenience and accessibility for participants, particularly those facing geographical or mobility constraints.

Electronic informed consent and remote recruitment strategies: DCTs utilize streamlined electronic consent processes enabling participants to review trial information, provide consent, and complete necessary documentation remotely. Online advertising and virtual prescreening strategies expand participant reach and improve diversity. Targeted remote recruitment methods overcome geographical limitations, expediting participant enrollment.

Real-world data integration and analysis: DCTs embrace real-world data sources, including electronic health records, claims data, wearable devices and patient registries, and other sources to gain a comprehensive understanding of patient experiences and treatment outcomes in real-life settings to supplement traditional clinical data, fostering a more comprehensive understanding of treatment outcomes and safety profiles. This integration enhances the analysis of trial results and provides valuable insights beyond controlled environments.

Benefits of Decentralized Clinical Trials, 2 3

Decentralized clinical trials offer numerous advantages over traditional models:

Improved participant diversity and access: DCTs break down geographical barriers, enabling broader participation and diverse representation including individuals from rural or underserved areas and those with limited mobility, leading to more inclusive, generalizable, and applicable study results.

Enhanced patient engagement and retention: By leveraging digital tools and remote interactions, DCTs foster greater participant engagement and retention rates. By reducing travel and in-person visits, DCTs alleviate participant burden, leading to improved engagement, higher retention rates/ reducing dropout rates, and more accurate and reliable data collection.

Reduced burden on participants: Remote data collection through digital tools and wearables simplifies the trial experience, minimizing the disruption to participants' daily lives and potentially increasing study adherence.

Increased efficiency and accelerated timelines: DCTs eliminate or minimize logistical challenges associated with site visits such as site initiation, monitoring, and data collection, reducing time and costs, enabling more efficient study conduct and enabling faster trial completion.

Cost Savings and Resource Optimization: DCTs can result in significant cost savings by reducing the need for physical infrastructure and in-person visits. Furthermore, the utilization of real-world data can enhance trial design, reduce the number of required participants, and optimize resource allocation making trials more cost-effective and sustainable.

Challenges and Considerations in Decentralized Clinical Trial 4

While DCTs offer promising opportunities, several challenges must be addressed:

Regulatory and ethical considerations: Adhering to evolving regulations and ethical guidelines is crucial to ensure participant protection, data privacy, and trial integrity.

Data privacy and security concerns: Protecting participant data during remote data collection, storage, and transmission requires robust security measures and adherence to data protection regulations.

Digital literacy and access disparities: Ensuring equitable access to technology and addressing disparities in digital literacy among diverse populations are essential to avoid exacerbating healthcare inequalities.

Integration with existing healthcare systems and infrastructure: Seamless integration of decentralized trial technologies with existing healthcare systems and infrastructure is necessary to ensure data interoperability, streamline workflows, and facilitate efficient collaboration among stakeholders.

Ensuring data quality and reliability: Implementing robust data collection, monitoring, and quality assurance processes is vital to maintain the integrity and validity of trial data generated remotely.

Flexible Supply Chain Management5: Is going to be the engine of a successful DCT. Fig1 provides insight to the multi layered logistical demands for a patient-centric (decentralized) trial compared to a traditional site-centric trial.

Figure 1.6 Patient Centric Approaches/DCTs Require Agile Logistics (and 3rd party logistic providers) to Manage the Different Demands

Case Studies and Success Stories

Several successful decentralized clinical trials have demonstrated the potential of this approach across various therapeutic areas. These studies have showcased improved participant recruitment, enhanced data collection, and successful trial outcomes. Examples include remote monitoring of patients with chronic conditions, virtual patient visits for mental health trials and follow-ups, decentralized trials for rare diseases, and mobile applications for data collection have shown promising results.

One notable success story is the ADAPTABLE trial 7 (Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long- term Effectiveness). ADAPTABLE, the first fully decentralized trial of its scale, involved over 15,000 participants. It aimed to determine the optimal aspirin dosage for preventing heart attacks and strokes. This award-winning study showcased the feasibility and advantages of a decentralized approach.

A case study conducted for a decentralized trial for Parkinson's disease demonstrated high participant engagement, reliable data collection, and positive patient experiences. Another study showcased a decentralized trial that successfully recruited a diverse participant population, including individuals from underserved communities.8

Notable players in the global virtual clinical trials market include Parexel International Corporation (with over 100 DCT’s9)10, which extended its strategic partnership with Medidata to advance the delivery of virtual/decentralized trials; Oracle and ObvioHealth, who collaborated to integrate diverse data sets for virtual trials in the Asia Pacific region; and Medable Inc., which launched a software solution simplifying virtual clinical trials for vaccines and reducing deployment time. These companies, along with other key players such as ICON, IQVIA, Medidata and Signant Health, are driving innovation and shaping the future of virtual clinical trials through technological advancements and strategic collaborations.

FDA Guidance and Industry Efforts11

The FDA has recognized the significant advantages of DCTs and released new guidance to improve their implementation for drugs, biological products, and medical devices. The FDA acknowledges the benefits of DCTs, including improving convenience for participants, alleviating caregiver burdens, expanding access to diverse populations, improving trial efficiencies, facilitating research on rare diseases, and enabling broader participation for populations with limited mobility.

The U.S. Food and Drug Administration (FDA) has taken additional steps to support the use of decentralized clinical trials (DCTs) for drugs, biologics, and devices. The FDA released a new draft guidance in May 2023 that provides recommendations for sponsors, investigators, and other stakeholders regarding the implementation of DCTs to advance medical product development and research.

The draft guidance builds upon previous recommendations issued in 2020, which provided clarity during the COVID-19 pandemic and associated disruptions. While the FDA's regulatory requirements for investigations of medical products are the same for DCTs and traditional site-based trials, the new guidance covers various topics, including design considerations, remote clinical trial visits, use of digital health technologies, roles and responsibilities of sponsors and investigators, informed consent processes, packaging and shipping of investigational products, and safety monitoring of trial participants.

Organizations such as the Decentralized Trials & Research Alliance (DTRA) 12 are actively working to create standards and a harmonized framework for stakeholders in the life sciences and healthcare industries. DTRA aims to accelerate the adoption of patient-focused, decentralized clinical trials and research through education and research collaborations.

The Future Implications of Decentralized Clinical Trials

Decentralized clinical trials hold immense potential for transforming the drug development and regulatory landscape. The future implications include:

Impact on drug development and regulatory processes: DCTs can facilitate faster and more efficient evaluation of interventions, leading to accelerated drug development timelines and regulatory decision-making.

Adoption challenges and strategies for implementation: Widespread adoption of DCTs requires collaboration among stakeholders, researchers, including sponsors, regulatory bodies, technology developers, healthcare providers, patient advocacy groups and patients, along with the development of standardized guidelines, tools, and best practices.

Evolving technologies and their role in advancing DCTs13: Continued advancements in wearable devices, remote monitoring technologies, artificial intelligence, machine learning and data analytics will further optimize DCT processes and outcomes.

Collaborative efforts and partnerships: Collaborations among pharmaceutical companies, research organizations, technology providers, and patient advocacy groups are vital to drive the adoption and success of decentralized clinical trials.

Ever wondered why the world is so quickly drifting towards DCT? 14

The global virtual clinical trials market has experienced significant growth, with a valuation of USD 8.3 billion in 2022. Looking ahead, it is projected to expand at a steady compound annual growth rate (CAGR) of 5.7% from 2023 to 2030 (with a forecasted revenue of USD 12.9 billion in 2030). This growth is primarily fueled by several factors, including the surge in research and development (R&D) activities, the increasing digitization of healthcare, and the widespread adoption of telehealth technologies. The future implications of DCTs are vast, including their potential to transform drug development processes, improve patient-centricity, and drive innovation in the healthcare sector.

North America emerged as the dominant region in the virtual clinical trials market, capturing the largest revenue share of 49.0% in 2022. This region is expected to maintain its stronghold throughout the forecast period. The market's dominance in North America can be attributed to several factors, including the region's robust investment in research and development (R&D), the rapid adoption of new technologies in clinical research, and strong government support for innovative healthcare initiatives. Market players in North America are also leveraging digital technologies to cater to the evolving needs of their clients. For example, Parexel has successfully conducted over 100 decentralized trials, employing hybrid and virtual approaches. Covance, on the other hand, has established approximately 1,900 LabCorp Patient Service

Centers across the United States, allowing trials to reach patients more conveniently.

In the Asia Pacific region, the market for virtual clinical trials is poised to exhibit the fastest compound annual growth rate (CAGR) of 6.8% during the forecast period. This growth is fueled by several factors, including the region's large patient pool, which enables easier recruitment of trial participants. Additionally, the increased penetration of digital technologies in the region has facilitated the adoption of virtual clinical trials, enhancing the efficiency and accessibility of clinical research.

As North America continues to drive innovation in virtual clinical trials, and Asia Pacific showcases significant growth potential, the global market for virtual clinical trials is set to witness substantial advancements. These trends reflect the ongoing transformation of the clinical research landscape, driven by the integration of digital technologies, evolving patient needs, and a focus on improving trial efficiency and patient outcomes.

Conclusion

Decentralization in clinical trials refers to a paradigm shift from the traditional site-centric model to a more patient- centric approach and offers a transformative path forward for the future of medical research. By embracing remote technologies, patient-centricity, and real-world data integration, DCTs address the limitations of traditional trials, leading to improved participant diversity, enhanced engagement, increased efficiency, and cost savings. While challenges remain, collaborative efforts and a commitment to regulatory compliance and ethical standards will pave the way for widespread adoption of decentralized clinical trials, ultimately advancing medical knowledge and improving patient outcomes.

With the support of regulatory guidance from the FDA and collaborative efforts from organizations like DTRA, the implementation of DCTs is gaining momentum. As the virtual clinical trial market continues to grow, stakeholders must embrace decentralization and leverage advancing technologies to unlock the full potential of DCTs. By doing so, we can shape a future where clinical trials are more inclusive, efficient, and impactful, ultimately advancing medical innovation and improving the lives of patients worldwide.

References:

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6. https://www.contractpharma.com/issues/2021-06-01/view_features/flexible-supply-chain-development-the- engine-of-decentralized-trials/

7. https://www.medidata.com/en/life-science-resources/medidata-blog/decentralized-clinical-trials-case-study- collection/

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11. https://finance.yahoo.com/news/fda-inspires-confidence-decentralized-clinical- 133100156.html?guccounter=1&guce_referrer=aHR0cHM6Ly93d3cuZ29vZ2xlLmNvbS8&guce_referrer_sig=AQAAAKJGH N9u_PbgUMfN7KWBlI3QEpp1k5n0XQcc3YFs_LoKk1t634i59Hksxalq- OBxMuERhdcId2b_jk99CGtMXwqnBnJTunxaSd7ntGNrHnkNkgCU9kvYW- 5xiYNOFtJAJZKhQtU7aa6dtdR9w_e3RaJJjj7UTYK0i4KfPCjGH3ID

12. https://www.federalregister.gov/documents/2023/05/03/2023-09399/decentralized-clinical-trials-for-drugs-biological- products-and-devices-draft-guidance-for-industry

13. https://www.fda.gov/news-events/press-announcements/fda-takes-additional-steps-advance-decentralized-clinical-trials

14. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/decentralized-clinical-trials-drugs- biological-products-and-devices

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17. https://www.grandviewresearch.com/industry-analysis/virtual-clinical-trials-market