Refining, Rethinking & Decentralizing Clinical Research

Reducing study cycle times and making research more accessible to patients have been among the biopharmaceutical industry’s most pressing challenges long before the COVID-19 pandemic disrupted business as usual. Expensive to launch, lengthy to conduct, and burdensome for both patients and investigators, traditional studies using brick-and-mortar sites may also fail to enroll a diverse enough patient cohort to assess the drug’s real-world use in a real-world population accurately—thereby missing the opportunity to provide critical, if not requisite, data to regulators, payers and providers.

This long-acknowledged focus on making the study process more efficient and accessible has certainly yielded incremental progress, but as the industry’s response to the pandemic has demonstrated clearly, no approach to improve trial operations has arguably been as successful as that as decentralization. And as we look ahead to conducting research in the post-pandemic world, it will be critical for sponsors and CROs to continue incorporating decentralized tools and technologies not just as an emergency stop-gap measure to ensure trial continuity, but also as part of a broader, more patient-centered approach to study design and conduct that can be applied to studies in each stage of development.

New opportunities, new discourse

Decentralized Clinical Trials (DCTs)—generally defined as studies that use telemedicine and/or digital health technologies to conduct some or all trial activities outside of traditional trial sites—were not borne during the pandemic at all. Digitally enabled patient-engagement tools have helped to accelerate trial enrollment for at least a decade, yet industry’s uptake of DCT tools and technologies has been slow amidst perceptions of increased operational challenges and regulatory uncertainty. But with study sites shuttered around the world in early 2020, DTC adoption grew substantially, out of need. Encouraged by FDA guidance to consider alternative approaches to in-person monitoring, sponsors and CROs were quick to incorporate digital technologies into existing trials. A November/December 2020 study from the Tufts Center for the Study of Drug Development, for example, found that 55% of active clinical trials transitioned to remote and virtual models during the pandemic, partially decentralizing trials by adding DCT methods to existing trial protocols.

This accelerated adoption has in turn elevated the need for continued discourse and cooperation toward common standards and operational procedures for integrating DCT elements into traditional clinical development plans. To that end, an excellent report from the Association of Clinical Research Organizations (ACRO) contrasts a traditional trial with a DCT to provide a quality framework for each unique step of the process and where a DCT model may present new challenges and considerations. Similarly, the Clinical Trial Transformation Initiative (CTTI) developed recommendations for addressing the logistical, legal and regulatory concerns related to certain aspects of DTC trial design and conduct. And lastly, newly established collaborative groups such as the Decentralized Trials & Research Alliance (DTRA) are working to accelerate DCT adoption through education and research, further proving the value of integrating decentralized tools and methods into clinical research.

New networks, new sites

The substantial activity in the DCT space is both encouraging and necessary. The same Tufts CSDD Impact Report showing that more than half of trials transitioned to remote and virtual models during the pandemic also found that more than 60% of investigators were unfamiliar with remote trial processes and solutions before the pandemic—an extraordinarily large number who likely required time-consuming, individualized training. Although such resource-heavy, study-specific training was/is certainly appropriate for continuity during the pandemic, converting traditional study sites to virtual study sites reactively adds significant time and cost to the clinical trial cycle time and cannot be considered a feasible long-term strategy.

A proactive DCT approach, by contrast, harnesses multiple investigator and patient networks to reduce site start-up time from months to weeks, then utilizes a centralized team of remote coordinators and mobile healthcare providers to maximize trial efficiency and enrich the patient experience. Indeed, increasing patient engagement is cited by ACRO experts as the main advantage of a decentralized trial, and actions such as gathering patient input during the development process and using patient-reported outcomes as endpoints all work to increase patient satisfaction and retention. For studies with challenging-to-enroll populations—such as oncology, CNS disorders and rare diseases—an integrated DCT strategy leveraging each of these patient-centered components would allow sponsors and CROs to conduct trials faster, more efficiently, and more aligned with both patient-important outcomes and regulator expectations.

In the real world

In addition to being appropriate and effective for many specialty populations, a DCT approach is also an extraordinarily efficient method for longer duration, real-world studies such as those for labeling changes, registries, long-term follow up, pharmacovigilance, outcomes research and pharmacoeconomic studies. By using a virtual, or meta-site, network that is not limited by geography, trial sponsors and CROs conducting these low-touch, resource-heavy studies can reduce start-up time, accelerate enrollment, and obtain a patient cohort more representative of the target population. These types of studies can truly maximize the potential of telemedicine, a suddenly very critical—and patient-preferred—component for collecting real-world data in a socially distanced world.

Looking ahead, granular clinical data gleaned from DCT tools and technologies can be used alongside other real-world data to create custom-curated longitudinal datasets to help answer a wide range of research questions. Data from sources such as medical records, claims data, and disease registries can be integrated seamlessly with DCT-generated data to provide regulators, payers and providers with accurate real-world evidence about a drug’s real-world use—valuable information that is often unattainable through traditional randomized clinical trials.

It is precisely this flexibility, this adaptability, that will ultimately lead biopharma sponsors and CROs to integrate DCT tools and methodologies into most of their clinical development programs. Learnings from studies that rushed and retrofitted DTC technologies into existing trials during the pandemic will help inform which elements to refine and rethink, and more importantly, which elements are most appropriate for specific therapeutic areas or patient populations. With this knowledge, we’ll soon see DCT applications evolve from being one-off and experimental to strategic and integrated as part of a broader, patient-centered study design that aims to get the right treatment to the right patients.