Heart Failure Clinical Trial Operations During the COVID-19 Pandemic

As of May 2020, 32% of sites had resumed clinical research activities, 27% planned to loosen restrictions in the next 2 to 3 months, and 41% had no plans to resume. There was considerable variation in where sites obtained guidance when determining how to resume clinical research activities: 5.2% followed federal guidance, 28% used state guidelines, and 7.2% used city/county guidance. Over half of reporting sites used a source not listed or were not aware of specific guidance.

A wide spectrum of comfort-level with respect to clinical research staff returning to the hospital was reported. Forty-two percent of responders reported at least some degree of fear associated with returning, 32% expressed little to no fear, and 26% reported feeling neutral. Fifty-nine percent reported not having clinical research staff furloughed, and 96% of sites had not experienced permanent staff termination.

Discussion

The results of this survey demonstrate the extent to which COVID-19 has obstructed various aspects of HF site-based research. Over half of CONNECT-HF sites have had major disruptions or complete cessation of all HF clinical research activity with substantial research coordinator work unable to be completed virtually. Furthermore, plans and guidance used to reopen HF research activities were variable.

To our knowledge, this survey represents the first attempt to quantify the impact of COVID-19 on site-based clinical research. This survey demonstrates how COVID-19 has identified inefficiencies in the clinical trial ecosystem. During the COVID-19 pandemic, regulatory agencies have advocated for operating clinical research programs with flexibility; ensuring the safety of trial participants, maintaining compliance with good clinical practice, and minimizing risk to trial integrity.^3,4 Unfortunately, these recommendations do not provide tangible ways to ensure continuation of research activity. By reducing in-person visits to keep participants and staff safe, it is unclear how slowed enrollment, delayed follow-up visits, and not having ways for reliable safety assessment will affect future outcomes of actively enrolling clinical trials. Because CONNECT-HF is a cluster-randomized trial that promotes guideline-based care and thus is low risk to patients, it is suited to converting to virtual enrollment and follow-up. Trials of novel therapeutics or for new therapeutic indications may not have this same flexibility given higher stakes in potential direct patient effects.

Regulatory and professional society recommendations also lack guidance on when or how to resume in-person clinical research operations.^3,4 This is reflected in variable responses about timing of reopening and guidance for reopening. A substantial number of survey responders expressed significant fear about returning to work. We did not assess whether fear of COVID-19 exposure would make research staff less likely to approach patients for research participation, though this would provide further justification for creation of robust digital platforms to conduct important research related activity. We also did not assess how patients will perceive enrollment in clinical trials as COVID-19 restrictions are lifted. Finally, this survey was created to ascertain changes to HF research activities in general; however, these findings may not be generalizable to broader cardiovascular research.

Conclusions

The COVID-19 pandemic has led to widespread disruption in the daily delivery of health care with a significant impact on HF clinical trials. This study demonstrated that COVID-19 has significantly interrupted HF site-based research activities across the United States, staff has limited access to avenues for virtual work, and plans to resume activities are varied. Conversion to virtual platforms, when feasible, would potentially help alleviate many of these issues.

Footnotes