Five Years of Discovery, the Critical Care Research Network

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Several years before the COVID-19 pandemic uprooted healthcare worldwide, the Society of Critical Care Medicine (SCCM) launched a task force to identify gaps in critical care research and determine how SCCM could address them. Within two years, this effort led to the establishment of Discovery, the Critical Care Research Network, and the timing could not have been more fortuitous.

Now five years old, Discovery created a much-needed infrastructure for critical care research, including the collection of vital data on hospitalized COVID-19 patients early in the pandemic, in the form of the Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry. “Without Discovery, initiatives such as the VIRUS COVID-19 Registry likely would have existed but only as educational initiatives to provide resources for ICU departments and hospitals in need,” said principal investigator Rahul Kashyap, MD, MBA. “Thanks to Discovery, the registry has become a foundation for collecting standardized clinical data on patient treatment and outcomes.”
 
The VIRUS COVID-19 study has spawned more than a dozen published articles and more than 120 ancillary research proposals by study participants. The registry is just one aspect of Discovery. Other major Discovery initiatives include the Structured Team-based Optimal Patient-Centered Care for Virus COVID-19 (STOP-VIRUS) learning collaborative and Severe Acute Respiratory Infection – Preparedness (SARI-PREP). Through  Discovery clinical investigators meetings, more than 31 research projects have been endorsed and numerous researchers have found a collaborative environment where they can pursue critical care research. But let’s back up for a moment.

Discovery Is Born

In 2012, Critical Care Medicine published an article about the need for critical care research and funding. In 2014, this article prompted the SCCM Council to appoint 11 members to the Research Network Task Force, which was chaired by Greg S. Martin, MD, MSc, FCCM (SCCM’s 2021-2022 president) and Vinay M. Nadkarni, MD, FCCM. The task force explored the activities of existing critical care trial groups and collaborated with United States Critical Illness and Injury Trials (USCIIT) and Critical Care Pharmacotherapy Trials Network (CCPTN) to form a new research network. Discovery was launched in 2017 at the 46th Critical Care Congress. That same year, the first in-person Discovery clinical investigators meeting was held at the National Institutes of Health (NIH) offices in Bethesda, Maryland, which was also attended by federal funding program officers.
 
Discovery’s five-year plan for 2017 through 2021 focused on building organizational infrastructure, program operations, and national and international collaboration. The plan included the following metrics, all of which were met by April 2021:

1. Secure extramural funding for Discovery programs
   • Funding for legacy Discovery programs was provided by NIH, Patient-Centered Outcomes Research Institute (PCORI), Agency for Healthcare Research and Quality (AHRQ), and private foundations.
   • New Discovery programs were funded by the Centers for Disease Control and Prevention (CDC) Foundation; Gordon and Betty Moore Foundation; Military Prototype Advancement Initiative/Department of Defense; Janssen Research & Development, LLC; and CURE ID, a U.S. Food and Drug Administration (FDA) initiative.
2. Provide evidence that Discovery funding leads to additional research grant funding within the network
   • SCCM committed $2.3 million to Discovery, the largest investment the SCCM Council has ever made outside of funding headquarters. SCCM continues to contribute $100,000 in grant funding each year to support investigators via Discovery intramural grants. These investigators and their projects have received additional grant funding:
     • Tài Pham, MD: Breathing Efforts in ARDS (BEARDS) is now called Incidence of Dyssynchronous Spontaneous Breathing Effort, Breath-stacking and Reverse Triggering in Early ARDS. This multi-institutional research is funded through Unity Health Toronto and is recruiting globally.
     • Amelia Barwise, MB, PhD, BCh, BAO: Nested Observational Cohort to Evaluate Diagnostic Error and Delay in the Critically Ill is now funded through the Gordon and Betty Moore Foundation.
3. Publish studies in high-impact journals
   • Several articles have been published in high-impact journals with an author byline that includes “on behalf of Discovery, the Critical Care Research Network of the Society of Critical Care Medicine.”
   • Recent highlights include:
     • The VICTAS randomized clinical trial published in the February 2021 issue of JAMA.  This study aimed to determine whether a combination of vitamin C, thiamine, and hydrocortisone every 6 hours increases ventilator- and vasopressor-free days compared with placebo in patients with sepsis.
     • A VIRUS: COVID-19 Registry article published in the December 2021 issue of JAMA Network Open. This international study found that patients hospitalized with COVID-19 who had a combination of high blood pressure, obesity, diabetes, or other conditions associated with metabolic syndrome were at much higher risk of acute respiratory distress syndrome and death.
4. Provide a complete range of data-coordinating activities using standardized processes and procedures
   • SARI-PREP helped support Discovery infrastructure by laying the groundwork for a consortium focused on improving clinical care through a better understanding of emerging and seasonal respiratory diseases and their treatments.
5. Develop publicly available datasets related to Discovery research
   • The VIRUS COVID-19 Registry and ICU Liberation Quality Improvement Collaborative were included in publicly available databases.
6. Develop a databank of common data elements across multiple Discovery studies to serve as a resource for future studies
   • The foundational work for development of the Critical Care Data Dictionary (C2D2), led by Discovery, substantially influenced the creation of the VIRUS COVID-19 Registry and the VIRUS/CURE ID collaboration (funded in 2021).
7. Be recognized by the NIH as promoting quality research related to critical illness
   • Yearly Discovery meetings are held at NIH (2020 and 2021 meetings were virtual), with multiple program officers presenting.

How Discovery Works

Discovery features three main areas of focus: infrastructure, a clinical investigator proposal mechanism, and education.
 
Infrastructure
The infrastructure was designed to support a self-sustaining network and functions as a data and clinical coordination center. The infrastructure was instrumental in quickly launching a registry when the World Health Organization announced the COVID-19 pandemic on March 17, 2020. Within a few days, several SCCM members discussed the need to create a registry and, on March 31, the Discovery VIRUS: COVID-19 Registry was launched to hospitals worldwide. Within six weeks, 25 sites had signed up and more than 3400 COVID-19 hospital admissions had been entered, with sites collecting patient characteristics, treatment strategies, and outcomes. Today, more than 300 sites participate, and the registry includes nearly 70,000 hospital admissions. The registry was supported by grants from the Gordon and Betty Moore Foundation and Janssen Research & Development, LLC.
 
The VIRUS: COVID-19 Registry enabled hospitals to be part of a registry without committing extensive resources to creating their own registries. The grants supported a cohort of sites that enabled data automation, which reduced the burden of manual data collection and data entry. When the next pandemic occurs, this mechanism can be used to collect data on a large scale to help address care and improve outcomes. With a grant from the U.S. Department of Health and Human Services’ Assistant Secretary for Planning and Evaluation (ASPE), the FDA contracted with Discovery to automate the data collection using automation tools on a larger scale.
 
The Discovery VIRUS: COVID-19 Registry (and its ancillary arm, STOP-VIRUS) and SARI-PREP are ongoing observational studies, with Discovery functioning as a data coordinating center and/or clinical coordinating center. SARI-PREP, a multicenter consortium funded by the CDC Foundation, built an infrastructure that lays the groundwork for improving clinical care through a better understanding of emerging and seasonal respiratory diseases (including influenza A and B, SARS-CoV-2, and other novel viral infections causing outbreaks) and treatments. The STOP-VIRUS ICU Learning Collaborative helps participants rapidly evaluate and effectively implement best practice recommendations from the ever-evolving body of knowledge related to the care of critically ill patients with COVID-19. The STOP-VIRUS collaborative features 12 participating hospitals and has been funded by the CDC and support from the VIRUS Registry through April 2022.
 
Clinical Investigator Proposal Mechanism
Through the clinical investigator proposal mechanism, researchers can submit studies through an online portal. Discovery provides details and guidance on getting started. Proposals are scored using a modified version of the NIH review scoring system, with each proposal receiving a score of 1 through 9, with lower scores better. Two reviewers provide an impact score for the proposal. Those scoring below the benchmark of 3.5 are endorsed. Investigators can leverage this network to receive feedback from a larger group by networking with other investigators, recruiting other sites into their study and, for approved projects, receiving endorsement letters when applying for funding. Researchers present their proposed studies at clinical investigators meetings, which take place three times a year.
 
Education
Still in development, the goal of Discovery’s educational function is to provide mentorship to investigators to help them build their research portfolio. Discovery also funded a small pilot for a clinical practice-embedded randomized control trial with the goal of supporting development and deployment of a practice-embedded adaptive platform to develop safe and effective drug treatments for hospitalized patients with COVID-19, in collaboration with FDA CURE ID and academic health institutions.

Discovery Activities

To date, 15 Discovery clinical investigators meetings have been held and 83 proposals have been received. Six proposals have become Discovery programs, meaning they have matured programmatically to the point of requiring their own organizational structure within Discovery. Programs usually have substantial peer-reviewed funding and, because of their size and complexity, have their own program publication oversight committees. Current programs are:

• SARI-PREP
• VIRUS: COVID-19 Registry

As of January 2022, more than 35 proposals have been become endorsed projects, meaning they are the highest-ranked proposals from Discovery clinical investigators meetings and must remain active and provide periodic updates to the steering committee.
 

What’s Next for Discovery?

Discovery’s mission is to be a multiprofessional research network of junior, mid-career, and senior investigators that conducts and disseminates clinical, translational, and implementation research designed to improve outcomes in critically ill and injured patients, in support of the SCCM mission. Its vision is to be a comprehensive international network that fosters collaborative, patient-centric critical care research by all members of the multiprofessional ICU team.
 
“The first five years of Discovery have been extremely productive and successful. As Discovery grows beyond its infancy, the initiative’s goals focus on conducting robust, high-quality, multicenter, observational, and randomized clinical research studies,” said Sheila A. Alexander, BSN, PhD, RN, FCCM, chair of the Discovery Steering Committee. “These studies test interventions that can improve the quality of life or quality of death in patients with or at risk for critical illness across the spectrum of disease from prevention to recovery.”
 
This may include reliable national and international benchmarking, quality improvement, and emergency preparedness efforts. “Discovery also is committed to growing a bench of clinical and translational researchers and developing a sustainable infrastructure and funding for long-term support of SCCM’s research mission,” Dr. Alexander said. “As we have learned throughout COVID-19, these worthy goals are vital to ensuring we can better manage the next pandemic or any critical care illnesses.”
   

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Posted: 4/7/2022 | 0 comments