U-M clinical registry harmonizes data to support global fight against COVID-19

As epidemiologists and researchers around the world race to discover ways to treat the novel coronavirus, a registry developed by a U-M team is supporting the fight by organizing COVID-19 clinical data to advance critical research across the globe.

Launched shortly after Michigan's first COVID-19 case was confirmed in March 2020, the COVID-19 Rapid Response Registry serves as a resource for researchers to analyze treatment trends and effects, hospital-level projections and to assess future research questions. The registry operates with support from the Michigan Institute for Clinical and Health Research (MICHR) and as a partner site of the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC), a network of 488 organizations in 37 countries (as of June 2020). 

"Our registry aims to provide researchers and clinicians with a centralized and comprehensive resource of COVID-19 patient data, to help propel science and to inform clinical decisions based on rapidly evolving evidence," says Emily Somers, Ph.D., Sc.M., registry director and an epidemiologist and associate professor of internal medicine at U-M Medical School. She oversees the registry, along with Emily Martin, Ph.D., M.P.H., associate professor of epidemiology at the School of Public Health. Both are members of the U-M Institute for Healthcare Policy and Innovation. 

Somers reflects on the rapid launch of the registry, key findings so far, and the importance of global research coordination in fighting the pandemic. 

Why are registries critical to understanding and treating new diseases like the novel coronavirus?

Somers: Every day counts in a public health crisis and a responsibility as an epidemiologist is to quickly aggregate and analyze data to provide as much insight as possible. With a brand new health threat, such as this novel coronavirus (SARS-CoV-2), we do not have clinical trial evidence to support therapeutics for prevention or treatment of the disease. The starting point for answering questions about a new disease is high-quality, descriptive data. Surveillance and registries may not be innovative, but are essential for understanding disease and facilitating research. Our registry, combined with data collected from other ISARIC sites across the globe, is playing a critical role in providing the best available data to help inform clinical decision-making, in as close to real-time as possible.  

Your team launched the registry within two weeks of Michigan's first confirmed case of COVID-19. How did you develop the registry in such a short amount of time? 

Somers: The roll-out of the registry was certainly a whirlwind. Our amazing team of researchers, supported by incredible technical and research administrative staff working toward a common goal, completed a process that typically takes a year in less than two weeks. Never have I seen a contract move so quickly! Interdisciplinary collaboration, funding, and administrative support through MICHR were critical to making this possible.

Our team, which includes biostatisticians, pharmacists, and clinicians in specialties ranging from infectious diseases to emergency medicine, worked around the clock to develop a data resource that could be used by U-M researchers and with investigators across the globe. We were one of the first U.S. sites to establish a partnership with ISARIC, which in collaboration with the World Health Organization, had previously developed open-access protocols and data tools in response to prior epidemics that could be adapted for this emerging infectious disease. While we supplemented ISARIC tools to fit our local needs and clinical questions, not having to reinvent the wheel by creating a registry from scratch allowed us to move swiftly.

With the registry up and running, your team and other U-M researchers have begun analyzing the data. What are the focus areas of the research currently?

Somers: Our initial focus has been evaluating the effectiveness of drugs repurposed to treat patients with COVID-19. Such drugs are FDA-approved for other purposes, thus accessible as treatment options despite uncertainty about whether they would benefit patients with COVID-19. Early in the pandemic, the most immediately actionable evidence that we could provide was from the analysis of observational, “real-world” data – allowing us to support front-line clinicians' treatment decisions in the absence of data from randomized controlled trials.

Some of our researchers are also trying to understand the risk factors for severe disease or factors that may influence individual patient outcomes of COVID-19. Others are trying to understand COVID-19's impact on special patient populations. For example, in collaboration with a team led by Pratima Sharma, M.B.B.S., M.D., M.S., we have examined COVID-19 outcomes in solid organ transplant recipients.

These focus areas are just the start. There will be many longer-term research questions that come out of this registry, as treatment and prevention options evolve and as patient follow-up accrues. 

What have you been able to learn from the registry since the March launch?

Somers: Through an observational analysis of the registry's data, we have published an article in the journal Clinical Infectious Diseases on an immunosuppressive drug called tocilizumab, which has been repurposed for the treatment of COVID-19. Originally designed for rheumatoid arthritis, our study found that a single dose of tocilizumab was associated with a 45% lower risk of death among critically ill patients with COVID-19. Patients were also shown to be more likely to be out of the hospital or off a ventilator one month after treatment than those who did not receive the drug. However, the treatment landscape is rapidly changing, and we are eagerly awaiting results from randomized controlled trials and larger populations.  

Beyond our recent research, we can attest to the critical need to have the infrastructure in place to deploy against an unexpected, large-scale health threat like the COVID-19 pandemic. Without the robust infrastructure of the University, collaboration across several schools and departments, and the support provided by MICHR  and its funding through the Clinical and Translational Science Awards (CTSA) program, we would not have been able to establish the registry so quickly or contribute to the research efforts of the international community.

In a recent article published in The Lancet Infectious Diseases, you and fellow co-authors/ISARIC site leaders discuss your efforts to harmonize data and foster international research collaboration amid the pandemic. Why are global research coordination and data harmonization so vital to the fight against COVID-19?

Somers: As a participating ISARIC site, our registry's data are harmonized with data from around the world, which means that no matter which country or individual site the data originated from, it is organized and coded in a uniform manner designed by expert consensus, which allows for clinically relevant and efficient analyses to be conducted. Such data harmonization seems like it should be standard practice within the international research community, but it is actually quite uncommon. 

In our Lancet Infectious Diseases article, we outline several reasons why global clinical research collaboration is absolutely critical to addressing infectious disease outbreaks like COVID-19. As we state, the speed of research in an outbreak needs to match that of the pathogen in order to yield results in a timeframe likely to benefit patients. International coordination -- as opposed to research conducted on an ad-hoc basis and in silos, using different methodologies and designs -- propels the science forward faster.

We also make the point that teamwork and collegiality tend to be undervalued as measures of academic excellence. One of the most gratifying aspects of working on the registry has been the opportunity to form new collaborations and (virtual) friendships with colleagues from across U-M and the globe, all demonstrating mutual respect and appreciation for one another. The remarkable pace of progress that we are experiencing is a testament to genuine teamwork.

Related articles:

• “Global outbreak research: harmony not hegemony,” The Lancet Infectious Diseases. DOI: 10.1016/S1473-3099(20)30440-0
• Observational study finds drug that calms' cytokine storm' associated with 45% lower risk of dying among COVID-19 patients on ventilators 
• "Tocilizumab for treatment of mechanically ventilated patients with COVID-19," Clinical Infectious Diseases. DOI:10.1093/cid/ciaa954