Challenges and Best Practices
Using surveys, webinars, interviews, and observation from site and VA Central Office personnel, the ORD identified specific variables that prevented the VAMCs from quickly starting up as a clinical trial site. We also documented strategies, solutions, and recommendations for improving startup time lines. These were organized into 8 categories: (1) site infrastructure needs and capabilities; (2) study management roles and responsibilities; (3) educational resources and training; (4) local review requirements and procedures; (5) study design demands; (6) contracting and budgeting; (7) central-level systems and processes; and (8) communication between external partners and within the VA.
Site Infrastructure Needs and Capabilities
A primary impediment to rapid study startup was a lack of basic infrastructure, including staff, space, and the agility necessary for the changing demands of high-priority, high-enrolling trials. This observation is not unique to the VA.7 Initially, certain facilities located in hot spots where COVID-19 was more prevalent became high-interest targets for study placement, despite varying degrees of available research infrastructure. Furthermore, pandemic shutdowns and quarantines permitted fewer employees onsite. This resulted in inadequate staffing in personnel needed to support required startup activities and those needed to handle the high volume of study participants who were being recruited, screened, enrolled, and followed. Additionally, as clinical care needs and infection control practices were prioritized, clinical research space was often appropriated for these needs, making it difficult to find the space to conduct trials. Lastly, supply chain issues also posed unique challenges, sometimes making it difficult for participating VAMCs to obtain needed materials, such as IV solution bags of specific sizes and contents, safety injection needles, and IV line filters.
The VA was able to use central purchasing/contracting at coordinating centers or the VA Central Office to support investigators and assist with finding supplies and clinical research space. VAMCs with research operating budgets to cover startup costs were better positioned to handle funding delays. During the pandemic, the ORD further contracted to supply administrative support to research offices to address regulatory and other requirements needed for startup activities. The ability to expand such central contracts to procure clinical research staff and outpatient clinical research space may also prove useful in meeting key needs at a site.
Management Roles and Responsibilities
Ambiguous and variable roles and responsibilities among the various partners and stakeholders represented a challenge given the large-scale, national, or international operations involved in the trials. VA attempts to operate uniformly were further limited given that each sponsor or group had preferred methods for operating and/or organizing work under urgent time lines. For example, one trial involved a coordinating center, a contract research organization, and federal partners that each worked with individual sites. Consequently, VA study teams would receive messages that were conflicting or unclear.
The VA learned that studies need a single “source of truth” and/or central command structure in times of urgency. To mitigate conflicting messages, vaccine trials relied on a clearinghouse through the PRP to interpret requirements or work on behalf of all sites before key actions were taken. For studies with the NIAID, the VA relied on experienced staff at the CSP coordinating center at the Perry Point, Maryland, VAMC before beginning. This approach especially helped with the challenges of understaffing and sites’ lack of familiarity with complex platform trial designs and already-established network practices within the ACTIV-2 and ACTIV-3 studies.
Educational Resources and Training
Since VA participation in externally sponsored, multisite clinical trials traditionally relies on an individual VAMC study team and its local resources, transitioning to centralized approaches for COVID-19 multisite studies created barriers. Many VAMCs were unfamiliar with newer capabilities for more rapid regulatory reviews and approvals involving commercial institutional review boards (IRBs) and central VA information security and privacy reviews. While tools and resources were available to facilitate these processes, real-time use had not been fully tested. As a result, everyone had to learn as they went along.
The simultaneous establishment of workflows required the ORD to centralize operations and provide training and guidance to field personnel. Although many principal investigators and clinical research coordinators had trial experience, training required unlearning previous understandings of requirements to meet urgent time lines. ORD enterprise road maps, central tools, and training materials also were made available on a study-by-study basis. Open communication was vital to train on central study materials while opportunities to discuss, question, and share experiences and ideas were promoted. The ORD also sent regular emails to prepare for upcoming work and/or raise awareness of identified challenges.