RADx-UP Program Addresses Data Gaps in Underrepresented Communities

Guest post by Richard J. Hodes, MD, Director, National Institute on Aging, and Eliseo Pérez-Stable, MD, Director, National Institute on Minority Health and Health Disparities, NIH.

A few months into the COVID-19 pandemic, we shared how NIH was working to speed innovation in the development, commercialization, and implementation of technologies for COVID-19 through NIH’s Rapid Acceleration of Diagnostics (RADx) initiative.

Two years later, one of the RADx programs—RADx Underserved Populations (RADx-UP)—reflects on lessons learned that have broken the mold of standard research paradigms to address health disparities.

Use of Common Data Elements

RADx-UP has presented unique challenges in terms of data collection, privacy concerns, measurement standardization, principles of data-sharing, and the opportunity to reexamine community-engaged research. Establishment of Common Data Elements (CDEs)—standardized, precisely defined questions paired with a set of allowable responses used systematically across different sites, studies, or clinical trials to ensure that the whole is greater than the sum of its parts—are not commonly used in community-engaged research. Use of CDEs enables data harmonization, aggregation, and analysis of related data across study sites as well as the ability to investigate relationships among data in unrelated data sets. CDEs can also lend statistical power to analyses of data for small subpopulations typically underrepresented in research.

RADx-UP is a community-engaged research program that builds on years of developing partnerships between communities and scientists. RADx-UP has funded 127 research projects with sites in every state and six U.S. territories as well as a RADx-UP Coordination and Data Collection Center (CDCC). RADx-UP assesses the needs and barriers related to COVID-19 testing and increase access to COVID-19 testing in underserved and vulnerable populations experiencing the highest rates of disparities in morbidity and mortality.

The COVID-19 pandemic necessitated establishing RADx-UP and its associated CDEs with unprecedented speed relying heavily on data elements derived from those already defined in the NIH-based PhenX Toolkit and Disaster Research Response (DR2) resources. The short time frame for this process did not allow for as extensive collaboration and input from RADx-UP investigators and community partners that would have been ideal. Additionally, many researchers, especially community partners engaged in RADx-UP projects, were not familiar with CDE data collection practices. As a result, CDE questionnaires had to be modified as studies progressed to better suit the needs of the consortium and investigators new to CDE collection had to be familiarized with these processes quickly. NIH program officers, NIH RADx-UP and CDCC leadership and engagement impact teams (EITs)—staff liaisons provided by the CDCC that link RADx-UP research teams to testing, data, and community-engagement resources—helped research teams implement and adjust CDE collection, ensured alignment across consortium research teams, and assisted with other data-related issues that arose.

All RADx programs are required to collect a standardized set of CDEs, including sociodemographic, medical history, and health status elements with the intent to provide researchers rapid access to data for secondary research analyses in the RADx Data Hub, the central repository for RADx data. However, implementation of CDEs in the context of underserved communities in the rapidly evolving COVID-19 pandemic presented complex issues for consideration.

Some of these issues included data privacy, the risk of re-identification of underserved and undocumented populations, and data collection burden on participants as well as researchers. The privacy of health data is protected under federal law. The RADx-UP program instituted measures to ensure program participants’ data remain protected and de-identified using a token-based hashing algorithm methodology that allows researchers to share individual-level participant data without exposing personally identifiable information. To address data collection and respondent burden concerns, projects modified questions to allow some flexibility in expanding response options more appropriate to some underserved communities. The CDCC also developed COLECTIV, a digital interface for projects to directly enter data into the data repository and included gateway questions to relieve respondent burden.

Respect for Tribal Data Sovereignty

RADx-UP leadership and investigators recognized that additional considerations for tribal sovereignty, practices, and policies needed to be addressed for projects that include American Indian and Alaska Native (AI/AN) participants. Through consultations with the NIH Tribal Advisory Committee and the broader AI/AN community and meetings with an informal RADx-UP AI/AN project working group established by the CDCC, NIH realized that deposition of tribal data into the RADx Data Hub would not meet the cultural, governance, or sovereignty needs of AI/AN RADx research data. In response, NIH hopes to establish a RADx Tribal Data Repository (TDR) responsible for the collection, protection, and sharing of data collected in AI/AN communities with respect for the practices and policies of Tribal data sovereignty. Applications for the repository have been solicited and NIH hopes to make an award for the TDR sometime in FY23.

Rapid Data Sharing

One of the largest hurdles the RADx-UP program has faced is implementing rapid sharing of research data for secondary analyses and to inform decision-making and public health practices related to the COVID-19 pandemic. RADx-UP research teams are expected to share their data on a timely cadence before data collection ends. This is a far more stringent practice relative to the current standard NIH data-sharing policy that requires data to be shared at the time of acceptance for publication of the main findings from the final data set. NIH and CDCC staff have worked together with the RADx research community to highlight the importance of and compliance with rapid data-sharing. Within the first six months, a total of 69 Phase 1 projects began transmitting CDE data to the RADx-UP CDCC. The COVID-19 pandemic posed a tremendous challenge, and NIH responded by collaborating with vulnerable and underserved communities. This collaboration has opened an unprecedented opportunity to build on a now established foundation for future research to address gaps in understanding the broader social, cultural, and structural factors that influence disparities in morbidity and mortality from COVID-19 and other diseases. Data collection and sharing efforts of the RADx-UP initiative comprise a significant contribution. Collaboration among the NIH, research investigators, and communities impacted by COVID-19 has been the catalyst. To learn more about RADx-UP, please visit a recent journal article available on PubMed.

Dr. Hodes has served as NIA director since 1993, overseeing studies of the biological, clinical, behavioral, and social aspects of aging. He has devoted his tenure to the development of a strong, diverse, and balanced research program focused on the genetics and biology of aging, basic and clinical studies aimed at reducing disease and disability, and investigation of the behavioral and social aspects of aging. Ultimately, these efforts have one goal — improving the health and quality of life for older people and their families. As a leading researcher in the field of immunology, Dr. Hodes has published more than 250 peer-reviewed papers.

Dr. Pérez-Stable practiced primary care internal medicine for 37 years at the University of California, San Francisco before becoming the Director of NIMHD in 2015. His research interests have centered on improving the health of individuals from racial and ethnic minority communities through effective prevention interventions, understanding underlying causes of health disparities, and advancing patient-centered care for underserved populations. Recognized as a leader in Latino health care and disparities research, he spent 32 years leading research on smoking cessation and tobacco control in Latino populations in the United States and Latin America. Dr. Pérez-Stable has published more than 300 peer-reviewed papers.

NLM . . . Bridging the Gap between COVID-19 Data and Resources

Guest post by Stephen Sherry, PhD, Acting Director of the National Library of Medicine’s National Center for Biotechnology Information (NCBI), and Bart Trawick, PhD, Director of the NCBI Customer Services Division.

A little over two years ago, America woke to the emerging SARS-CoV-2 pandemic that would alter everyone’s perception of ‘normal’ in the months and years to follow. From the start, NLM’s technological infrastructure quickly bridged the gap between resources and action to support efforts to study, understand, and develop a plan of action to deal with the deadly virus that has claimed the lives of more than 6 million people worldwide according to the World Health Organization COVID-19 dashboard. NLM has worked throughout the pandemic to provide timely data and develop digital resources to help combat this global crisis.

NLM’s COVID-19 Resources

To assist in understanding the most fundamental questions surrounding the virus, NLM provides coronavirus-related tools and services centered around genetic information, literature, and clinical research protocols.

SARS-CoV-2 Gene Sequences in GenBank

In January 2020, NLM released the first complete severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome to the public through our GenBank database, the world’s largest database of publicly available genetic sequences. It’s a significant scientific community accomplishment to release a fully annotated viral genome within a month of its detection in a human population and NLM is proud to have played a role in this. This information was essential to scientists – because only with the genetic sequence could they begin to determine the specific properties of the virus and its evolutionary relationship to other viruses.

Creating a Lens to Information

An immediate challenge during the early months of the pandemic was the lack of a standardized vocabulary for talking about the virus and the disease it caused, COVID-19. This made searching the biomedical literature for coronavirus information difficult. To address this issue, NLM developed the LitCovid tool, which provided researchers with a current and curated literature hub for coronavirus information. Its handy classification system makes it easy for users to find the type of information they are interested in (e.g., “Mechanism” or “Treatment”). To further expand the application of this tool, NLM incorporated it into the PubMed Clinical Queries search interface.

Bringing COVID-19 Information to Your Fingertips

One of NLM’s biggest challenges amid the demand for COVID-19 information has been organizing all the data, tools, and resources related to SARS-CoV-2 and COVID-19. To date, there are over 3 million SARS-CoV-2–related sequencing experiments in NLM’s Sequence Read Archive (SRA), the world’s largest publicly available repository of high-throughput genetic sequencing data; 4 million SARS-CoV-2 sequences in GenBank; more than 7,500 registered coronavirus clinical trials in NLM’s ClinicalTrials.gov, the world’s largest clinical trial registry and results database; and 285,000 COVID-19 articles in PubMed Central (PMC), NLM’s digital archive of nearly 8 million freely accessible, full-text biomedical and life sciences journal articles. To organize and make this wealth of information findable, we created the NCBI SARS-CoV-2 resources page and regularly update the NLM homepage with news and information to guide users to relevant information.

Information When You Need It Most

Patients and their families also need access to up-to-date, reliable information, and our MedlinePlus web resource added a COVID-19 page to address this. For people seeking information on clinical studies related to COVID-19, our ClinicalTrials.gov resource provides this, along with a dedicated page that breaks down all COVID-19 studies by funding source.

NLM Answers the Call for Access to COVID-19 Publications

NLM answered the call from the White House Office of Science and Technology Policy and science policy leaders of other nations by collaborating with publishers and scholarly societies to provide free and immediate public access to all coronavirus-related publications and associated data via PubMed Central (PMC) as part of its Public Health Emergency COVID-19 Initiative.

This initiative also enabled artificial intelligence researchers to contribute to the COVID-19 response effort by making more than 200,000 full-text articles available in formats and under license terms that enabled computational analysis as part of efforts such as the COVID-19 Open Research Dataset (CORD-19) Challenge and Text Retrieval Conference (TREC) COVID Challenge.  These global challenges aimed to improve and apply natural language processing and other AI techniques to coronavirus literature in an effort to generate new insights into the disease.

Reaching More People in More Ways

As the Nation’s archive for biotechnology information, we rely upon scientists to freely share data with us so that others may benefit. To assist submitters in getting this data into our sequence archives, we quickly worked to automate and simplify submissions, expedite data analysis, and prioritize data release to within minutes of submission. NLM investments ensured that database management work continues to scale in tandem with increased submission rates.

None of this work would have been possible without the support of NIH leadership and the efforts of NLM staff who accomplished great feats during a time of transition to remote work. We will apply the lessons learned during this period to serve the continuing needs of our community as the biology continues to evolve around us.

As NCBI Acting Director, Dr. Sherry plans, directs, and manages the research, development, and technical operations of the National Center for Biotechnology Information. He has 25 years of experience performing research, education, and data resource management involving human variation, genetics, and genomics. Dr. Sherry is a graduate of the Pennsylvania State University.

 As Director of the NCBI Customer Services Division, Dr. Trawick works to connect customers with the vast information resources available from NCBI. Dr. Trawick is a graduate of Texas A&M University and the University of Texas Health Science Center at Houston.

Pandemic Decision Fatigue: How Can We Help?

As we enter the third year of the COVID-19 pandemic, I cannot help but be acutely aware of the challenges faced by our frontline workers, from nurses and physicians to grocery store workers and public safety personnel, to teachers, bus drivers, and childcare workers, not to mention the parents of school aged and small children. Despite the recent reduction in case rates for the most recent SARS-CoV-2 variant, hospitalizations remain high, and death is still a familiar consequence to the COVID-19 infection. Clinicians continue to deal with shifting priorities and experience the futility of care more often than ever. Decisions for self-care during the pandemic come frequently supported with guidance that changes over time and may result in confusion and questions – When to mask? How long to quarantine? Boosters? When? What to say to the person in the grocery line who is wearing her mask on her chin?

At the NIH, the rapid pace of work persists. Like others in workplaces around the country, we must keep our base operations moving while working at breakneck speed to deploy new research practices, make available the data and literature needed to understand this complex infectious disease, and estimate its course.

My personal experience during these two years has been a strange mixture of unusually high work demands, unanticipated complexities in the delivery of routine services, and an odd sense of solitude in working from home. I have been safely protected from exposures to large groups and mass transit. Because of the nature of technology, and the resources of the federal government, we at NLM have been able to effectively work from home as we strive to get information out to scientists and society at the speed of a pandemic. So, because my work life seems so safe and easy compared to those of other nurses and physicians and parents, I often wonder – what can I do to help?

I posed this question to some of my other Institute and Center directors at NIH – who are also wondering how can we best advance science—NIH Turning Discovery into Healthwhile responding to the pandemic with the resources of research and knowledge? It was heartening, and also disheartening, to hear concerns echoed by others.

However, through these conversations, a few themes emerged. NIH takes seriously its responsibility to build public trust and demonstrate the value of public funding. We must strive to be true to our mission, which is to seek fundamental knowledge about the nature and behavior of living systems. We must balance the urgency of the moment with safeguarding and nurturing the progress of science. There is no better example than that afforded by the rapid production of vaccines against the SARS-CoV-2 virus, which emerged from almost two decades of basic science investigation. It’s through initiatives such as the NIH Community Engagement Alliance (CEAL) Against COVID-19 Disparities, efficiently launched in the early days of the pandemic, that led to the deployment of community-sensitive testing strategies and opened the door to community delivery of the very vaccines that resulted from basic work at the NIH.

So, what I can I do to help? It is our job at the NLM to acquire, organize, preserve, and disseminate biomedical knowledge. We need to listen to the voices of the pandemic and to heed the urgent calls for information to guide clinicians and patients. We need to pandemic-ready our resources, so that our policy partnerships and communication pathways produce, in the first weeks of a pandemic, the arrangements that help us unlock the literature related to coronaviruses and make it freely accessible to all. We need to deploy our staff for temporary assignments, whether to help launch the Rapid Acceleration of Diagnostics (RADx) or to envision and design the pathology project within the RECOVER: Researching COVID to Enhance Recovery initiative.

We need to accelerate access to viral sequences to stimulate new types of testing, vaccines, and therapeutics. And we need to promote access to freely available professional literature, like the work of Charlene Dewey and colleagues, to help create a culture that will sustain the clinician workforce during the pandemic.

Yes, I still have a valid nursing license, and I still wonder if I should volunteer to give vaccines or provide relief to staff at a local ER. Frankly, at this point in my life, I think I am better at being the director of NLM—doing as much as I can to help while maintaining our commitment to acquire, collect, disseminate, and preserve the knowledge of biomedicine and health—but who knows what future may bring!

Have you experienced pandemic decision fatigue? How can NLM support you?

Pursuing Data-Driven Responses to Public Health Threats

In my 11th grade civics class, I learned about how a bill becomes a law, and I‘ll bet some of you can even remember the steps. Today, I want to introduce you to another way that the federal government takes actions – executive orders. As head of the executive branch, the president can issue an executive order to manage operations of the federal government.

In light of the COVID-19 pandemic, President Biden has issued executive orders to accelerate the country’s ability to respond to public health threats.

This is where I come in. As Director of the National Library of Medicine (NLM) and a member of the leadership team of the National Institutes of Health, I’m part of a group developing the implementation plan for the Executive Order entitled Ensuring a Data-Driven Response to COVID-19 and Future High-Consequence Public Health Threats.

This order directs the heads of all executive departments and agencies to work on COVID-19 and pandemic-related data issues. This includes making data that is relevant to high-consequence public health threats accessible to everyone, reviewing existing public health data systems to issue recommendations for addressing areas for improvement, and reviewing the workforce capacity for advanced information technology and data management. And, like all good government work, a report summarizing findings and providing recommendations will be issued.

Since March 2021, I have been meeting 2 to 3 times a month with public health and health data experts across the U.S. Department of Health & Human Services (HHS). Our committee includes staff from the Office of the National Coordinator for Health Information Technology, Food and Drug Administration, Centers for Disease Control and Prevention, Centers for Medicare & Medicaid Services, and Office of the Assistant Secretary for Planning and Evaluation.

After creating a work plan, our group arranged briefings with many other groups, including public health officials from states and territories, representatives from major health care systems, and the public, among others. We reviewed many initiatives to promote open data, data sharing, and data protection across the government sphere. We learned about the challenges of developing and adopting data standards, and the ability of different groups to come together to make data more useful in preparing the country to anticipate and respond to high-consequence public health threats. We discussed future strategies for data management and data protection, new analytical models, and workforce development initiatives. Our working group provided a report to the Office of Science and Technology Policy (OSTP), handing it off to the next team who will take the work process and keep moving it toward completion. In coordination with the National Science and Technology Council, OSTP will develop a plan for advancing innovation in public health data and analytics.

This was a beneficial experience for me, and I certainly learned a great deal. Implementing a public health response system requires engagement with many HHS divisions, each of which brings a unique perspective and experience. I also developed new relationships based on trust and collaboration with these colleagues. At NLM, we have experts in data standards and data collection, and we oversee vast data repositories, so we have substantial domain-specific knowledge to contribute. I drew frequently on the knowledge and expertise of NLM staff to inform the process through analyses of information and the preparation of reports. I am grateful for all who helped and supported me.

I believe our country is prepared to have the data necessary to prevent, detect, and respond to future high-consequence public health threats. This is yet another way that NLM is helping shape data-powered health for the future. What else can we do for you?

Thanks, Dr. Fauci!

Perhaps the most famous NIH staffer right now is Anthony Fauci, MD, Director of the National Institute of Allergy and Infectious Diseases (NIAID), and one of the leading voices throughout the COVID-19 pandemic. Prepared by more than 50 years of government service and research on infectious diseases, Dr. Fauci is a public servant who brings reason, expertise, and a keen sense of how to mobilize the public health sector to act against this unprecedented threat to public health.

Like many others around the country and the world, my family and I think of Dr. Fauci as “our doctor.” He speaks to us, giving a personal response to ensure the public’s health. He understands the challenges of having family at a distance during times when travel and family gatherings are discouraged to reduce the spread of infection. He shares the joys of those reunions—full of hugs from family and friends—so long missed. It’s amazing to me that Dr. Fauci has been able to convey such warmth and concern to the world and be the deliverer of trusted knowledge in such a personal manner. More than once, conversation at a family dinner or on a family phone call has included the question, “But what does Dr. Fauci think about . . .?” followed by heartfelt wishes of gratitude from my mother and siblings!

I am privileged to be part of the NIH leadership team who meets weekly to advance the mission of the world’s largest research enterprise. While we address wide ranging issues from advancing biomedical science to NIH infrastructure and operations, discussions about NIH’s response to the COVID-19 pandemic still dominate. Like others, I find Tony a wise and experienced colleague, thoughtful in his contributions, and quick to bring a sometimes much-needed touch of humor into complicated conversations. I marvel at his stamina and the breadth of issues that engage his mind.

Tony Fauci has built a superb team of scientists, clinicians, and administrators within NIAID. The dedication and intellectual generosity evident in his contributions to our efforts are evident across NIAID – clearly an inspirational leader motivates and inspires!

So please join me in expressing gratitude to my colleague, Tony Fauci – a national treasure!

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