Decentralized Clinical Trials: Preparing for the Next Quantum Leap 

The clinical trial landscape is transforming and pivoting away from its reliance on data collection within the confines of traditional research facilities. Today’s decentralized clinical trial (DCT) encompasses innovative approaches like digital data collection, telemedicine consultations, remote monitoring, and more. In the past, clinical trials followed a rigid, conventional approach, necessitating on-site visits and in-person interactions with the study team. However, the challenges inherent in this model, coupled with the compelling need to prioritize patient-centricity, have sparked a remarkable shift towards the seamless integration of DCT elements into the fabric of clinical trials. This transformation not only enhances efficiency and flexibility, but also aligns with a broader vision of a more patient-centered future for healthcare. 

The journey towards DCTs dates to the early 2000s when forward-thinking biopharmaceutical companies began exploring various approaches, including 1) a 2003 feasibility study on “Internet trials,” 2) the granting of a United States patent for “Trial over the Internet” in 2007, and 3) Pfizer’s successful completion of its inaugural decentralized clinical trial in 2011 under the leadership of Craig Lipset. 

However, the COVID-19 pandemic accelerated the adoption of DCT out of sheer necessity. With clinics and doctor’s offices shuttered, pharmaceutical companies faced critical decisions regarding the continuity of patient treatments. Many had to swiftly pivot towards DCT methods to ensure uninterrupted collection of crucial data. Regulatory bodies, including the FDA’s Center for Drug Evaluation and Research, recognized the vital role of DCT and expressed its commitment to supporting its implementation by the end of 2023.  

Today, pharmaceutical companies are at a crossroads. They must either embrace DCT elements within their drug discovery processes or risk being left behind. The advantages of adopting DCT are manifold: expediting drug development timelines, facilitating patient recruitment and diversity, improving patient retention and adherence to trial protocols, enabling remote monitoring, and enhancing data collection and analysis, to name just a few. 

Life Sciences executives must seize these opportunities and embrace decentralized models, harness the technological advancements, and optimize trial design and execution. By doing so, they can drive innovation, enhance patient experiences, and achieve meaningful advancements. 

What are Decentralized Clinical Trials 

The industry has witnessed a transformation in trial design and execution through DCTs, which are trials that leverage technology, processes, and services to reduce or eliminate the need for participants to physically visit traditional research sites.  

Traditional (or Centralized) Clinical Trials 

Traditional clinical trials follow the conventional, centralized model where participants must visit a physical research site for various aspects of the trial, such as enrollment, administration of investigational products, data collection, and monitoring.  A research site — or sites — serves as the center for trial design and execution, where study activities primarily take place. While these trials have been the standard approach for many years, they pose challenges such as geographical limitations, patient burden, and higher costs associated with site operations and logistics.  

Decentralized, Hybrid Clinical Trials 

Decentralized hybrid clinical trials (DHCT) combine both traditional and decentralized elements. These trials incorporate the use of digital technologies and remote data collection methods to reduce the need for participants to visit research sites. This approach offers increased adherence to the study protocol while reducing patient/caregiver burden. A notable DHCT is 2016 Duke university trial, ADAPTABLE, designed to identify the optimal dose for secondary prevention in patients with Atherosclerotic cardiovascular disease. ADAPTABLE leveraged DHCT by using a patient portal to collect patient-reported outcomes, accessed electronic health records, and collected eConsent, while also having 40 locations for in-person patient observation. 

Decentralized Site-less Clinical Trials

Decentralized site-less clinical trials eliminate the need for physical research sites altogether. Participants primarily engage remotely through digital platforms and technologies, enabling broader recruitment, increased diversity, reduced geographical constraints, and the potential to streamline trial operations, lower costs, and enhance participant engagement. However, it also introduces regulatory compliance and data privacy challenges and the need to ensure adequate support and resources for participants. One such site-less trial is the 2011 Pfizer trial, REMOTE, a trial designed to test the effectiveness of Tolterodine ER on overactive bladders. This trial was conducted at home, with all participants self-administering the drug and collecting and reporting their own data.  

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Approach to DCT Adoption 

When pharmaceutical companies consider building or acquiring their own DCT capabilities, it is crucial for them to establish clear goals and guiding principles to define the desired outcomes and constraints. According to Craig Lipset, co-chair of the Decentralized Trials & Research Alliance (DTRA) and founder of Clinical Innovation Partners, “Innovation in DCTs should be accompanied by guardrails to ensure participant safety, data integrity, and consistent measurement approaches across both traditional trials and DCTs.”  

One starting point in defining DCT goals is to identify the minimum viable product (MVP) for the organization. The MVP for DCTs might focus, for instance, on ensuring trial continuity during major disruptions that limit patients’ ability to visit physical sites regularly. Identifying the MVP typically involves a prioritization exercise, considering factors like ease of implementation, value to trial continuity, and the timing of implementation relative to the trial duration. MVPs are most beneficial when designed into the study from the outset or implemented in parallel to complement a more traditional protocol. During the COVID-19 pandemic, key capabilities such as home health care, direct-to-patient medication shipments, use of wearables, and telemedicine proved essential in maintaining trial integrity and continuity. 

In addition to the MVP, aligning on guiding principles and measuring the success of DCTs are other critical aspects. A few examples include:  

1. Target Audience: Identify your target audience and their needs. Ensure that your MVP caters to their pain points and preferences. Clarify whether your DCT solution is primarily for patients, caregivers, Principal Investigators (PIs), or site staff.  

2. Feasibility and Resources: Evaluate the resources required for developing and maintaining the MVP. Consider factors such as your team’s capabilities, available budget, time constraints, and the technological feasibility of your solution. Decide whether to handle development in-house or explore outsourcing options, weighing the pros and cons of each approach.  

3. Competitive Analysis: Conduct a thorough competitive analysis to understand what other studies in the field are doing or, perhaps more importantly, what they are not doing. Identifying gaps or areas where your DCT can offer a unique advantage can be a momentous change in gaining a competitive edge. 

4. Scalability and Flexibility: Ensure that your MVP is designed with scalability and flexibility in mind. Think beyond the immediate project and consider how this solution can be leveraged across other pipeline programs. Scalability is critical for long-term success and maximizing the return on investment.  

5. Success Metrics: Define clear and measurable success metrics to track the impact of your DCT initiative. Key performance indicators should include the speed and diversity of patient recruitment, the ability to maintain trial continuity during periods of uncertainty (as exemplified by the COVID-19 pandemic), cost reduction compared to traditional trial models, and an evaluation of the necessity and efficiency of site visits. 

By establishing clear goals, guiding principles, and defining success metrics, pharmaceutical companies can effectively align their DCT strategies with desired outcomes and data integrity. 

The Future of DCT 

The future of DCTs presents an exciting challenge marked by a lack of standardized approaches. Whether it is driven by unique disease state, complex patient population, or specific trial objectives, there is no one-size-fits all formula to follow. However, now is the time to seize the opportunity presented by DCT and integrate it into the future landscape of clinical trial design. 

One potential option for future DCTs is the integration of electronic Clinical Outcome Assessments (eCOA) technology. eCOA technology empowers the collection of Patient-Reported Outcomes (ePRO), allowing patients to report their own health outcomes and experiences. ePRO patient surveys or visit questionnaires play a crucial role in collecting insights directly from participants, enriching the understanding of treatment outcomes. These technologies enable consistent data collection both “on site” and “at home” where questionnaires and assessments are completed on digital devices, such as tablets or handhelds.  

Wearable devices also offer the opportunity for continuous monitoring of various biometric and physiological parameters, providing real-time data to enhance trial outcomes. A notable emerging trend in wearable technology is its role in cardiac safety. Cardiac safety remains a top factor contributing to the failure of clinical trials. Companies actively seek eCOA technology partners to monitor cardiac data, ensuring patient safety not only in traditional trial settings, but also within the evolving DCT environment. 

As DCTs continue to evolve, leveraging eCOA, ePRO, and wearables will enhance the development of patient-centric trials. These advancements can improve data collection, elevate patient experiences, and drive more effective and efficient clinical research in the future. 

Challenges for DCT Implementation 

Implementing decentralized clinical trials (DCTs) presents several significant challenges that demand strategic solutions.  

Patient Recruitment and Retention Complexity 

DCTs often rely on participants’ motivation and their ability to engage with remote monitoring technologies. Maintaining a diverse and representative study population becomes particularly challenging in this context. Attracting and retaining participants while ensuring inclusivity is paramount for the success of DCTs. 

Data Quality and Integrity 

Remote data collection and reliance on patient-reported outcomes introduce potential sources of bias and inaccuracies. Thus, robust measures for data validation and adherence to stringent regulatory standards become imperative. Ensuring the data collected is both accurate and reliable is a non-negotiable aspect of DCTs. 

Technology Infrastructure and Data Security 

Protecting patient privacy and safeguarding the confidentiality of sensitive health data require substantial investments and ongoing maintenance. Ensuring data security is not just a regulatory requirement, but also a fundamental ethical responsibility. The stakes are high, and industry players must commit to upholding the highest standards. 

While there is still much to understand and uncover when it comes to DCT, there is increasing pressure to continue to innovate while ensuring participant safety, data integrity, and regulatory compliance. Close collaboration across industry stakeholders, regulatory bodies, and technology providers will prove crucial in enabling efficient and effective clinical research, and DCT methods will play a critical role in shaping this advancement. 

Conclusion

The evolution of clinical trial practices from traditional, on-site models to DCT models marks a significant shift in the life science industry. DCT approaches have the potential to revolutionize the way we conduct studies, offering several advantages such as increased enrollment and improved patient retention. These models break down geographical barriers, cater to patient preferences, and simultaneously enhance data quality while reducing costs.  

The patient-centric nature of DCTs aligns with the goal of improving overall trial experiences and promoting inclusivity. In the current landscape, it is imperative for Life Sciences companies to seize these opportunities and embrace decentralized clinical trial models. By doing so, they can drive innovation, enhance patient experiences, achieve meaningful advancements, and deliver life changing therapies to their patients.