Leveraging Existing Infrastructure
Besides quickly organizing a central touchpoint for the VA COVID-19 research response, the ORD capitalized on its extensive nationwide infrastructure. One key component was the Cooperative Studies Program (CSP); the longstanding VA clinical research enterprise that supports the planning and conduct of large multicenter clinical trials and epidemiological studies. The CSP includes experts at 5 data and statistical coordinating centers, a clinical research pharmacy coordinating center, and 4 epidemiological resource centers.8 CSP studies provide definitive evidence for clinical practice and care of veterans and the nation. CSP’s CONFIRM trial (CSP 577) is the largest VA interventional study with > 50,000 veterans.9 CONFIRM followed the Trial of Varicella Zoster Vaccine for the Prevention of Herpes Zoster and Its Complications (CSP 403), which involved > 38,000 participants to evaluate a vaccine to reduce the burden of illness-associated herpes zoster (shingles). In the study, the vaccine markedly reduced the shingles burden of illness among older adults.10 These studies highlight the CSP cohort development ability as evidenced by the Million Veteran Program.11
VA Research, particularly through the CSP, contributed to multiple federal actions for COVID-19. The CSP had already established partnerships with federal and industry groups in multisite clinical trials and observational studies. During COVID-19, the ORD established a COVID-19 clinical trial master protocol framework: the VA CoronavirUs Research & Efficacy Studies network.9 The CSP also supported studies by the Coronavirus Prevention Network, the National Institute of Allergy and Infectious Disease (NIAID), and the US Food and Drug Administration (FDA). As such, the VA could translate requirements in working with an industry sponsor on the rapid execution of studies within a federal health care system. Much of the success arose when there was either earlier engagement in planning and/or existing familiarity among parties with operational and regulatory requirements.
Before the pandemic, the ORD had also been working on various external partnerships to increase opportunities for veterans in clinical trial participation, particularly for cancer, which Caroff and colleagues discuss further.12 A newly emerging Partnered Research Program (PRP) offered a strategy for participation in the major COVID-19 vaccine efficacy clinical trials. VA Research, through PRP and CSP, rapidly engaged others and managed critical communication (Table 1). In quickly pivoting to COVID-19 clinical studies, the VA also used the Networks of Dedicated Enrollment Sites (NODES), its site-based, CSP-supported infrastructure of existing investigators and coordinators with clinical, operational, and regulatory proficiency for large trials.13,14 Together, the CSP and PRP solidified the VA’s scientific, operational, and regulatory support basis for working with industry partners and federal agencies to conduct therapeutic and vaccine trials.
Speed, Knowledge, and Safety
The scope of VA Research partnerships covers several goals but can be broadly categorized in the following ways: research aimed at evaluating the efficacy of new treatments; development of infrastructure to facilitate more rapid and innovative approaches to research; and building connections within the health care system to take an enterprise approach to research.
Activities are not limited to COVID-19. The VA partners with federal entities on research primarily through interagency agreements whose authorities are derived from the Economy Act (31 USC § 1535). For industry and nonfederal groups, the VA enters into Cooperative Research and Development Agreements that are rooted in the Federal Technology Transfer Act (15 USC § 3710). Although the VA has experience in each of these processes, COVID-19 prompted many groups, existing partners and new ones, to engage with the VA. Consequently, the ORD needed to quickly understand the complexities of how to handle such engagements on a larger scale. The VA Research enterprise strategy also focused on facilitating these processes.
As part of VA integration goals, ORD leaders engaged VA clinical leaders, especially in Public Health, Preventive Medicine, Pharmacy Benefits Management, and Pathology and Laboratory services. The ORD also worked closely with operational leaders, including those responsible for the Veterans Integrated Service Networks and VAMC chiefs of staff and network chief medical officers. The ORD’s familiarity with coordinating complex activities for research further helped to organize nonresearch responses for clinical needs and resources to support the VA COVID-19 response. The Office of the Under Secretary for Health recognized VA Research’s critical role as part of the VA health care system. In turn, it served as a major champion to drive success among the active research efforts, especially the partnered efforts, responding to COVID-19. Continuously communicating support and offering resources for the agency’s overall COVID-19 response reinforced the positive impact of VA Research that extended beyond its traditional roles. That is, the research component of VHA was highlighted as an integral part of the COVID-19 response along with its clinical operations. This integrated approach was perhaps best demonstrated in a VHA-wide push to start and conduct the national vaccine efficacy trials.
Other COVID-19 research supported by the ORD included participation in the Mayo Clinic–led convalescent plasma expanded access treatment protocol, which had emerged as a potential therapeutic option.15 The ORD provided centralized regulatory support to nearly 100 VAMCs, helping to reduce inconsistencies in protocol approval processes for what was hoped to be a promising treatment for COVID-19.16 This rapid approach to address a real-time treatment option demonstrated the VA Research capability for swift mobilization in an emergency.
The ORD also coordinated with other federal agencies. For example, it collaborated with the US Department of Defense to begin a parallel observational study on COVID-19 infections and potential severe outcomes. The study enrolled > 3000 veterans who are being followed for up to 2 years to better understand the natural history and course of COVID-19.17 Other interagency efforts focused on vaccine and therapeutic trials, including Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) with the National Institutes of Health. In these activities, VA Research helped increase recruitment, particularly of a more diverse patient population, in helping to assess promising treatments.10
Motivated by its expanding portfolio of COVID-19 intervention studies, the VA also created a COVID-19 research registry for all VA investigators. This registry included almost 59,000 veterans who indicated a willingness to volunteer for clinical studies. This registry exemplified a long-standing tradition of veterans willing to serve their nation again in a time of need. Iaquinto and colleagues showcased how VHA programs (eg, Office of Healthcare Innovation and Learning) collaborated by expediting a study on 3D-printed swabs to address supply chain shortages. The study, which involved the FDA, showed that the printed swabs were as effective as commercially available ones.18 It provided evidence supporting the production and dissemination of a greater number of testing swabs to the public while also reducing the cost and time requirements (Table 2).
Altogether, these collaborative efforts advanced a transformative approach within the VA that was already happening but was accelerated by the pandemic. Such activities enabled greater understanding throughout the VA for how research is not merely complementary but an integrated part of how veterans receive health care. By giving opportunities to veterans to participate in studies, especially clinical studies, the VA created a path in which such expectations, understanding, and operations were more fluid.