Discussion

Our survey results show that there was a major negative impact on CTSA Hub CRC activity during the first year of the COVID-19 pandemic, with 79% of responding CRCs with inpatient units reporting greater than 50% declines in inpatient census and 32% reporting greater than 75% declines. There was also a negative impact on outpatient census, but the effect appeared to be less severe. The reasons for this are not entirely clear, but perhaps staffing constraints were less significant for outpatient research visits, which are shorter in duration, do not necessarily require RN staffing, and tend to be less staff-intensive. Given the widespread constraints on nontherapeutic clinical research activity early in the pandemic, it is highly likely that the remaining admissions and outpatient research visits were largely for therapeutic trials [Reference Subramain, Wangui-Verry, Sprenger, Comellas and Barlow3]. Our survey did not include questions regarding specific patient populations (e.g., elderly, immunocompromised, and cancer patients), but a few of the narrative responses indicated that investigators were particularly reluctant to conduct in-person visits for those vulnerable research participants if there were any other options.

These data confirm earlier institutional and CTSA-wide surveys and are not surprising, given the widespread mandated restrictions on non-COVID-related clinical research early in the pandemic [Reference Loucks, Tyson and Dorr2–Reference Flume, Berbari and Viera4,Reference Shah, Hoyo, Moussatche and Volkov6–Reference Melvin, Tandon, Rowe, Clohessy and Palermo8]. Additional common reasons for decreased activity reported in this and previous surveys include concerns for the safety of research participants, investigators, and staff, and staffing shortages.

Previous CTSA-wide surveys of CRCs were conducted in 2020, during the first year of the pandemic, when less was understood regarding COVID-19 transmission, personal protective equipment was limited, and COVID-19 vaccines had not yet been developed [Reference Ford, Johnson, Nichols, Rothwell, Dubinett and Naeim1–Reference Flume, Berbari and Viera4,Reference Shah, Hoyo, Moussatche and Volkov6,Reference Greenberg, Poole and Ford7]. Our survey is the first one that covers the second year of the pandemic, adding valuable insights to how CRCs started to recover from initial severe constraints on activities. We found that inpatient and outpatient research census improved from the first to the second year in most CRCs. However, census often remained below pre-pandemic levels, despite the easing of most institutional restrictions on clinical research activities. Reasons for this included continued safety concerns from participants and investigators and staffing shortages. Many CRCs reported that they mitigated the negative impact on research activities by pivoting to support COVID-related research, maintaining close coordination with institutional entities and investigators, implementing practices to mitigate risks to research personnel, and adopting innovative approaches to supporting clinical research during the pandemic, including eConsent, virtual visits, electronic source documentation, and home delivery of experimental therapeutic agents [Reference Ford, Johnson, Nichols, Rothwell, Dubinett and Naeim1–Reference Flume, Berbari and Viera4,Reference Odlaug, Crevel and Tosun9–Reference Thaman, Tafuto, Gélinas, Gaur and Neubauer11]. These latter approaches allowed outpatient clinical research to resume, but most would not be captured as CRC census.

Greater than half of the CRCs responding to the survey reported decreased revenue during the pandemic. CRCs are prohibited from funding direct research activities with CTSA award monies and rely heavily on revenue from investigator grants and contracts, as well as institutional support. For some CRCs, loss of revenue from non-COVID-related research activities was mitigated by increased revenue from COVID-related research. However, as COVID-related clinical research wanes and if non-COVID research census does not return to pre-pandemic levels, there may be long-term implications for CRC operating budgets.

Approximately half of CRCs were able to maintain staffing levels during the 2 years of the pandemic covered in this survey, but there were frequent reports of decreased staffing levels, increased turnover, and low morale, similar to previous reports from earlier in the pandemic [Reference Subramain, Wangui-Verry, Sprenger, Comellas and Barlow3]. These reports echo more widespread concerns regarding long-term effects of the pandemic on the nursing workforce.

CRCs have been major sites of support for early career investigators who conduct patient-oriented clinical research. The majority of CRCs responding to our survey reported that their early career investigators experienced significant challenges in continuing their research, confirming earlier reports [Reference McCormack, Bredella and Ingbar12–Reference Mayowski, Meagher and Althouse14]. It is hoped that these challenges will abate, but longer-term effects of the pandemic on career development should be monitored, with consideration of strategies to reverse this impact.

Our survey provided unique data regarding participation of CRCs in COVID-related research and its impact on non-COVID activities. The great majority of CRCs responding to our survey participated in COVID-related research efforts, including vaccine trials, noninterventional studies (e.g., biorepositories, serology studies, and diagnostic development), and therapeutic trials. CRC support spanned the spectrum of clinical research activities, including study start-up, regulatory support, training of clinical research staff, and conduct of study visits, confirming earlier reports [Reference Jayaweera, Flume and Singer5,Reference Thaman, Tafuto, Gélinas, Gaur and Neubauer11]. Participation in noninterventional studies was higher than in therapeutic trials, likely representing lower staffing barriers to conducting noninterventional studies. The proportion of overall effort devoted to COVID-related studies varied widely, which may reflect variability in patient numbers, staff availability, and resources that could be quickly deployed for large-scale vaccine trials or studies involving actively infected COVID-19 patients. It is a tribute to the robust CTSA CRC infrastructure that this pivot to COVID-related research was largely successful. In most cases, this did not interfere with non-COVID research and in fact helped maintain research census, although this was during a time when non-COVID research was constrained.

Despite the valuable information derived from our survey, especially regarding efforts during the second year of the pandemic, there are limitations to our data. Our response rate of 44% was lower than previous CTSA surveys and may limit the generalizability of our results. The geographic diversity of responses mitigates this limitation but does not eliminate it. In particular, there was relative underrepresentation among CTSA Hubs in Southern states, with 20% of Southern Hubs responding, compared to 43–67% of Hubs from other US regions. Given that some Southern states’ populations were disproportionately affected by the pandemic, this limits our ability to assess whether there was a differential impact of the pandemic on CRCs depending on region. In an effort to minimize the time commitment to complete the survey, we asked respondents to provide estimated answers to quantitative questions, rather than calculating exact numbers from their internal databases. This may have led to under- or overestimating numerical data. The broad range of possible responses to our quantitative questions did not allow for correlative analyses of potential relationships between changes in census and changes in revenue, staffing turnover or decreased workforce morale. Fewer respondents provided comments for some qualitative questions, limiting generalizability of these issues.

A number of publications from CTSA sites have outlined lessons learned from the COVID-19 pandemic and proposals to prepare the clinical research enterprise for future public health emergencies [Reference Ford, Johnson, Nichols, Rothwell, Dubinett and Naeim1–Reference Flume, Berbari and Viera4,Reference Shah, Hoyo, Moussatche and Volkov6,Reference Coller, Buse, Kimberly, Powderly and Zand15]. Our survey results underscore many of these findings, highlighting the value of a robust patient-oriented clinical research infrastructure that can rapidly respond to evolving events by reducing nonessential research activities, pivoting to innovative methods that allow clinical research to proceed in a virtual environment, and deploying CRCs’ considerable resources to support pandemic-related research [Reference Bobb, Ballance and Abbate16]. Previous publications have highlighted the additional role that CRCs and CTSA Hubs can play in prioritizing clinical research studies for enrollment of patients into COVID-related trials, utilizing fair and transparent criteria that include direct benefit to patients, avoidance of competition for enrollment, protection of providers, efficient use of limited resources, health disparities, and access to care [Reference Ford, Johnson, Nichols, Rothwell, Dubinett and Naeim1,Reference Thaman, Tafuto, Gélinas, Gaur and Neubauer11,Reference Bobb, Ballance and Abbate16].

While these are positive results, our survey also highlights the challenges that face CRCs in a rapidly evolving public health emergency and its aftermath. Many of the innovative approaches to conducting clinical research are likely to become permanent, as the pandemic hastened technology-driven solutions such as eConsent and remote study visits, and CRCs will need to evolve to provide support in nontraditional ways [Reference Loucks, Tyson and Dorr2,Reference Flume, Berbari and Viera4,Reference Melvin, Tandon, Rowe, Clohessy and Palermo8]. The current financial structure that supports CRC operating budgets may need to evolve as well, as on-site research admissions and visits may not always recover to pre-pandemic levels, and future clinical research growth is likely to incorporate these new approaches. Concerns regarding nursing staffing remain, as staff burn-out and turnover continues to constrain clinical as well as research activities across the country. Long-term solutions for the nursing staffing crisis are not yet clear, but CRCs can encourage staff retention and morale by supporting staff training in research methods and highlighting the unique rewards of clinical research, particularly research conducted at the local level. Finally, sharing lessons learned and plans for future readiness across the CTSA network of CRCs can be invaluable for avoiding pitfalls and highlighting successful operations during a time of unprecedented challenges. Previous CTSA publications have recommended that institutions complete readiness evaluations and put in place workflows, training, and liaison services that can be rapidly deployed for future public health emergencies [Reference Flume, Berbari and Viera4,Reference Shah, Hoyo, Moussatche and Volkov6,Reference Greenberg, Poole and Ford7,Reference Coller, Buse, Kimberly, Powderly and Zand15,Reference Keenoy, Lenze and Nicol17].