The US Department of Veterans Affairs (VA), through its Office of Research and Development (ORD), supports an extensive and experienced clinical research enterprise, including the first multisite trials in the US.1 These resources contribute to the ORD support for the largest US integrated health care system, with a primary focus on the care and well-being of veterans. While the history of VA research has facilitated the creation of an experienced and organized research enterprise, the COVID-19 pandemic challenged VA to contribute even more significantly. These challenges became pronounced given the urgency associated with standing up VA sites for both therapeutic and vaccine trials.
VA Clinical Research Enterprise
The VA recognized an early need for an organized research response not only to address operational challenges resulting from COVID-19 but also ensure that the agency would be ready to support new scientific efforts focused specifically on the virus and related outcomes.2 As a result, the ORD took decisive action first by establishing itself as a central headquarters for VA COVID-19 research activities, and second, by leveraging existing resources, initiatives, and infrastructure to develop new mechanisms that would ensure that the VA was well positioned to develop or participate in research endeavors being driven by the VA as well federal, industry, and non-VA partners.
Prior to the pandemic, the ORD, through its Cooperative Studies Program (CSP), had strategies to address challenges associated with clinical trial startup and improved efficient conduct.3 For example, the VA Network of Dedicated Enrollment Sites (NODES) is a consortium of 23 VA medical centers (VAMCs) dedicated to rapid startup and recruitment into VA-sponsored clinical trials. NODES provides site-level expertise on clinical trial management, including troubleshooting challenges that may occur during clinical research execution.4 Another initiative, Access to Clinical Trials (ACT) for Veterans, engaged industry, academic, patient advocacy, and other partners to identify potential regulatory and operational hurdles to efficient startup activities specific to externally sponsored multisite clinical trials. Under ACT for Veterans, stakeholders emphasized the importance of developing a single VA point of contact for external partners to work with to more efficiently understand and navigate the VA system. In turn, such a resource could be designed to facilitate substantive research and long-term relationships with compatible external partners. Targeted to launch in April 2020, the Partnered Research Program (PRP) was expedited to respond to the pandemic.
During the pandemic, new VA efforts included the creation of the VA CoronavirUs Research and Efficacy Studies (VA CURES) network, initially established as a clinical trial master protocol framework to support and maximize VA-funded COVID-19 trial efficiency.5 VA CURES joined the consortium of trials networks funded by the National Heart, Lung, and Blood Institute. It began treatment trials under Accelerating COVID-19 Therapeutic Interventions and Vaccination (ACTIV), specifically ACTIV-4. The VA also partnered with the National Institutes of Allergy and Infectious Diseases (NIAID) by organizing the VA International Coordinating Center (VA ICC) for other ACTIV trials (ACTIV-2 and -3). When approached to startup studies that included veterans and the VA health care system, these capabilities comprised the VA research response.
A Need for a New Approach
As the impact of the pandemic expanded and the need for effective treatments and vaccines grew, national calls were made to assess the capabilities and readiness of available clinical trials networks. Additionally, the US Department of Health and Human Services Biomedical Advanced Research and Development Authority, ACTIV, NIAID Division of Clinical Research and Division of AIDS, and many pharmaceutical companies were starting to roll out trials of new therapeutics and vaccines. These groups approached the VA to help evaluate the safety and efficacy of several therapeutics and vaccines because they recognized several advantages of the VA enterprise, including its position as the nation’s largest integrated health care system, its diverse patient population, and its expertise in conducting clinical trials.
Although the VA was well positioned as an important player in a collaborative investigational approach to COVID-19 research, these trials required startup approaches that were significantly different from those it had employed in traditional, prepandemic, clinical research. Despite the VA being a single federal agency, each VAMC conducting research establishes its own practices to address both operational and regulatory requirements. This structure results in individual units that operate under different standard operating procedures. Efforts must be taken centrally to organize them into a singular network for the entire health care system. During a national crisis, when there was a need for rapid trial startup to answer safety and efficacy questions and participate under a common approach to protocol execution, this variability was neither manageable nor acceptable. Additionally, the intense resource demands associated with such research, coupled with frequent reporting requirements by VA leaders, Congress, and the White House, required that VAMCs function more like a single unit. Therefore, the ORD needed to develop VAMCs’ abilities to work collectively toward a common goal, share knowledge and experience, and capitalize on potential efficiencies concerning legal, regulatory, and operational processes.
Beginning August 2020, 39 VAMCs joined 7 large-scale collaborative COVID-19 therapeutic and vaccine trials. Through its COVID-19 Research Response Team, the ORD identified, engaged, and directed appropriate resources to support the VAMC under a centralized framework for study management (Table). Centralized management not only afforded VAMCs the opportunity to work more collectively and efficiently but also provided an important advantage by enabling the VA to collect and organize its experiences (and on occasion data) to provide a base for continual learning and improvement efforts. While others have described efforts undertaken across networks to advance learning health systems, the VA’s national scope and integration of research and clinical care allow greater opportunities to learn in a practical setting.6