Author + information
- Harlan M. Krumholz, MD, SM, FACC, Co-Chair of the ACC Heart House Roundtable on Cardiovascular Clinical Research in the COVID-19 Era∗ ( and )
- James L. Januzzi Jr., MD, FACC, Co-Chair of the ACC Heart House Roundtable on Cardiovascular Clinical Research in the COVID-19 Era
- ↵∗Address for correspondence:
Dr. Harlan M. Krumholz, Yale School of Medicine, 1 Church Street, Suite 200, New Haven, Connecticut 06510.
The onset of the SARS-CoV-2 pandemic (coronavirus disease-2019 [COVID-19]) has had a profound effect on research. It has created an impetus for change, presented a wide range of challenges, and sparked an array of initiatives. In doing so, the pandemic has revealed threats to old models of knowledge generation and openings for new approaches. It is clear there is an unprecedented need for action.
To address the research challenges created by the pandemic, the American College of Cardiology (ACC) conducted a Heart House Roundtable on clinical research in the COVID-19 era. The ACC invited a range of experts to discuss the changing landscape and to identify opportunities to provide rapid research to support efforts to prevent, diagnose, and treat COVID-19 infection; to produce actionable insights about the effects of the pandemic on non–COVID-19 cardiovascular disease; and to address the need to continue and accelerate cardiovascular clinical research that remains urgently needed but that has encountered obstacles during the pandemic. The goal was to generate discussion, share insights, and produce recommendations. The Planning Committee, speakers, and participants who rapidly convened this unprecedented effort are listed in the Roundtable webpage (1).
The COVID-19 pandemic has had many effects on research. It created an urgent need for a pipeline for actionable knowledge generation to inform public health policies and practice, clinical care, and patient decisions. Evidence is needed regarding the direct effects of the virus as well as its indirect effect on cardiovascular care and patient behaviors; both inform important decisions moving forward in the pandemic. At the same time, the pandemic has disrupted and interrupted ongoing clinical research processes in ways that demand our attention and may ultimately change our approach. The Roundtable was designed to address both of these important topics, which involves all aspects of clinical research including recruitment, data collection, retention, and analysis.
Immediate Need for Rapid Knowledge About SARS-CoV-2
Before this year, there was no practical knowledge about SARS-CoV-2 and its manifestation as COVID-19. There were no research papers, textbook chapters, recorded lectures, or meaningful evidence about how COVID-19 spread or its clinical manifestations―let alone how to effectively prevent and treat it. What was recognized is the need to track and understand the diverse aspects of the spread and impact of the virus, encompassing its direct and indirect effects. At the outset of the spread of the virus in China, the cardiovascular implications of the infection were not well-appreciated. Moreover, the indirect effects on health care utilization and the marked reductions in visible cardiovascular events were not anticipated nor immediately studied.
Nevertheless, the medical research world responded with many reports from the front lines and many studies from a spectrum of health care organizations and academic centers. Although rapidly disseminated, there are concerns about the heterogeneity of the quality of these studies. Additionally, although the advent of preprint servers has facilitated scientific communication, preprint servers also enabled the dissemination of many preliminary—and weak—scientific studies. Medical peer-review journals appropriately accelerated their evaluations but have published many low-quality research papers, and even the highest-impact journals have had to rapidly retract recent COVID-19–related studies.
The Roundtable members appreciated the tension between the need for new evidence and the challenge of curating information from disparate sources of wide-ranging quality. Even publication in a top journal does not necessarily signal that an in-depth review was performed. The Roundtable recommendations sought to address the following challenges.
• Need for collaboration. The fragmentation of efforts and data was noted as a primary impediment to progress. Many small, underpowered, and often poorly designed clinical trials have provided conflicting evidence or will fail to produce the needed evidence base. Instead, there is a need for cooperation among investigators and the development of larger, coordinated efforts that could be completed rapidly and have the scientific rigor to influence practice. The RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial, bringing together institutions across the United Kingdom, is an example of what can be achieved by such a spirit of collaboration. There is also a need to embrace transparency and data sharing, with the idea of generating trust about the quality of the research and boosting the efforts of others.
• Need to leverage electronic real-world data sources. In the face of a rapidly spreading pandemic, speed needs to be a key feature of research. The traditional brute-force, labor-intensive, slow, and expensive approaches to research were viewed as problematic when speed and agility were at a premium. The Roundtable strongly endorsed more avid use of existing electronic real-world data sources to support investigations about the prevention, care, and outcomes of people at risk for or infected with COVID-19. These data sources might be able to support digital registries that reduce reliance on human abstraction and traditional case report forms. However, caution is obviously needed; data abstracted from clinical practice cannot be held to the same level as those from randomized-controlled trials, but they may nonetheless provide high-quality inferences. There will be a need to validate the quality of data from these sources, to recognize that different types of processing may influence the utility of the data in different ways, and to test which inferences could be trusted. There is also recognition of the need for information about data sources―particularly the provenance of the data―and the permissions that have accompanied them.
• Need to incorporate patient-reported outcome measures. There was a sentiment that real-world data sources were not sufficient, and that a need exists for incorporating the patient experience. Especially in the context of a new condition, it is important to understand the effects of such a condition from the patient’s point of view. Patient-reported outcome measures enable the collection of information in ways that can be standardized and compared; this facet of the research was considered essential.
• Need for long-term studies. There was recognition that many of the effects of the virus may take time to manifest, and concern was articulated about how early injuries may yield to long-term recovery; little research has been focused on the chronic effects of survivorship after COVID-19, which ultimately may affect tens of millions of patients. There is a need for long-term research that accounts for changes in pathophysiology and patient experience over time. This long-term research perspective is vital to fully understanding the effects of the virus and to developing the best means to address it at all stages.
• Need for expert curation of the scientific data. With the large amount of heterogeneous scientific information relevant to the pandemic being generated daily, there is a need for trusted organizations to provide expert perspectives and to help organize the high-quality data. This is accompanied by a need to translate relevant findings in ways that are accessible to clinicians, with an emphasis on what is actionable. The ACC is ideally positioned, through its COVID-19 Hub and extensive education offerings, to continue providing an essential service to health care professionals and patients globally by evaluating the science and educating people about its implications. Ultimately, although clinical practice guidelines may provide support to frontline clinicians, at a moment of dynamic change in the evidence it is ideal to have a rapid response to preprint postings and peer-reviewed publications―and to incorporate these perspectives into educational content that can be archived.
Need to Mitigate the Effect of COVID-19 on Clinical Research
The pandemic, in many institutions, led to an immediate suspension of clinical research. In some areas, this was done as clinical services were exhausted by the provision of care for patients with COVID-19, whereas in others it was done pre-emptively to prevent placing research participants at unnecessary risk. A critical concern is that COVID-19 outcomes introduced competing risks into studies, and that changing health care utilization patterns may have altered projected outcome rates for specific types of events. The Roundtable considered many areas that need attention to restore the ability of the research ecosystem to pursue non–COVID-19 research that remains urgently needed.
• Adoption of remote technologies. The pandemic has revealed the need to speed the testing and adoption of remote technologies to facilitate data acquisition and participant engagement. This includes the means to obtain e-consent, to gather participant permission to use real-world data sources, and to support protocolized data collection. The design of research needs to focus on reducing burden, broadening access, and enabling engagement without the need for face-to-face encounters―or at least minimizing them.
• Development and communication of safe practices. The Roundtable members expressed concern that potential participants would be deterred from participating in research because of fear of infection―or a reluctance to engage with the health care system for what was perceived as an optional encounter. There is a need to develop safe practices for research and to communicate information directly to individuals who are, or might be, enrolled in studies. There is a need to give people confidence that studies can be conducted without placing them at additional risk.
• Coordination with the regulatory agencies. The Roundtable recognized the need to coordinate with regulatory agencies for studies that have a role to play in regulatory approvals. Many studies in the field may be affected by how many people they can enroll and how many outcomes are accruing during the time of a pandemic. There are many questions about how regulatory agencies will treat research from this period. There will be a need for ongoing discussion about how best to salvage the research that has been in progress as well as research that is on the cusp of being launched. If the pandemic extends for a longer period, these decisions will have enduring relevance.
In conclusion, a unifying theme of the Roundtable was that research is facing considerable challenges and will likely not return to its previous form. There will be a need for collaboration among researchers, clinicians, policymakers, participants, and society to determine how best to proceed in the post-pandemic era. The Roundtable comments echoed the sentiment of a need to reconsider how research is performed, and to embrace the idea that new data sources and novel technologies have the potential to not only help circumvent the challenges of the pandemic, but also to open the door to much-needed and long-awaited changes. Such changes could favorably affect the speed and quality of research. The ACC has played a key role as a source of trusted knowledge since the inception of the COVID-19 pandemic and is poised to be a catalyst and convener of necessary changes in research standards moving forward.
- 2020 American College of Cardiology Foundation
- ↵Heart House Roundtable: Clinical Research in the COVID-19 Era. Available at:. https://www.acc.org/education-and-meetings/features/2020/05/cardiovascular-clinical-research-in-the-covid-19-era-heart-house-roundtable. 2272020.