tests
RADx Initiative: Bioengineering for COVID-19 at Unprecedented Speed and Scale
Posted on by Bruce J. Tromberg, Ph.D., National Institute of Biomedical Imaging and Bioengineering
As COVID-19 rapidly expanded throughout the world in April 2020, many in the biomedical technology community voiced significant concerns about the lack of available diagnostic tests. At that time, testing for SARS-CoV-2, the coronavirus that causes COVID-19, was conducted exclusively in clinical laboratories by order of a health-care provider. “Over the counter” (OTC) tests did not exist, and low complexity point of care (POC) platforms were rare. Fewer than 8 million tests were performed in the U.S. that month, and it was clear that we needed a radical transformation to make tests faster and more accessible.
By February 2022, driven by the Omicron variant surge, U.S. capacity had increased to a new record of more than 1.2 billion tests in a single month. Remarkably, the overwhelming majority of these—more than 85 percent—were “rapid tests” conducted in home and POC settings.
The story behind this practice-changing, “test-at-home” transformation is deeply rooted in technologic and manufacturing innovation. The NIH’s National Institute of Biomedical Imaging and Bioengineering (NIBIB), working collaboratively with multiple partners across NIH, government, academia, and the private sector, has been privileged to play a leading role in this effort via the Rapid Acceleration of Diagnostics (RADx®) initiative. On this two-year anniversary of RADx, we take a brief look back at its formation, impact, and potential for future growth.
On April 24, 2020, Congress recognized that testing was an urgent national need and appropriated $1.5 billion to NIH via an emergency supplement [1]. The goal was to substantially increase the number, type, and availability of diagnostic tests in only five to six months. Since the “normal” commercialization cycle for this type of diagnostic technology is typically more than five years, we needed an entirely new approach . . . fast.
The RADx initiative was launched just five days after that challenging Congressional directive [2]. Four NIH RADx programs were eventually created to support technology development and delivery, with the goal of matching test performance with community needs [3].The first two programs, RADx Tech and RADx Advanced Technology Platforms (ATP), were developed by NIBIB and focused on innovation for rapidly creating, scaling up, and deploying new technologies.
RADx Tech is built around NIBIB’s Point of Care Technologies Research Network (POCTRN) and includes core activities for technology review, test validation, clinical studies, regulatory authorization, and test deployment. Overall, the RADx Tech network includes approximately 900 participants from government, academia, and the private sector with unique capabilities and resources designed to decrease inherent risk and guide technologies from design and development to fully disseminated commercial products.
At the core of RADx Tech operations is the “innovation funnel” rapid review process, popularized as a shark tank [4]. A total of 824 complete applications were submitted during two open calls in a four-month period, beginning April 2020 and during a one-month period in June 2021. Forty-seven projects received phase 1 funding to validate and lower the inherent risk of developing these technologies. Meanwhile, 50 companies received phase 2 contracts to support FDA authorization studies and manufacturing expansion [5]
Beyond test development, RADx Tech has evolved to become a key contributor to the U.S. COVID-19 response. The RADx Independent Test Assessment Program (ITAP) was launched in October 2021 to accelerate regulatory authorization of new tests as a joint effort with the Food and Drug Administration (FDA) [6]. The ITAP acquires analytical and clinical performance data and works closely with FDA and manufacturers to shave weeks to months off the time it normally takes to receive Emergency Use Authorization (EUA).
The RADx Tech program also created a Variant Task Force to monitor the performance of tests against each new coronavirus “variant of concern” that emerges. This helps to ensure that marketed tests continue to remain effective. Other innovative RADx Tech projects include Say Yes! Covid Test, the first online free OTC test distribution program, and Project Rosa, which conducts real-time variant tracking across the country [7].
RADx Tech, by any measure, has exceeded even the most-optimistic expectations. In two years, RADx Tech-supported companies have received 44 EUAs and added approximately 2 billion tests and test products to the U.S. capacity. These remarkable numbers have steadily increased from more than16 million tests in September 2020, just five months after the program was established [8].
RADx Tech has also made significant contributions to the distribution of 1 billion free OTC tests via the government site, COVID.gov/tests. It has also provided critical guidance on serial testing and variants that have improved test performance and changed regulatory practice [9,10]. In addition, the RADx Mobile Application Reporting System (RADx MARS) reduces barriers to test reporting and test-to-treat strategies’ The latter offers immediate treatment options via telehealth or a POC location whenever a positive test result is reported. Finally, the When to Test website provides critical guidance on when and how to test for individuals, groups, and communities.
As we look to the future, RADx Tech has enormous potential to impact the U.S. response to other pathogens, diseases, and future pandemics. Major challenges going forward include improving home tests to work as well as lab platforms and building digital health networks for capturing and reporting test results to public health officials [11].
A recent editorial published in the journal Nature Biotechnology noted, “RADx has spawned a phalanx of diagnostic products to market in just 12 months. Its long-term impact on point of care, at-home, and population testing may be even more profound [12].” We are now poised to advance a new wave of precision medicine that’s led by innovative diagnostic technologies. It represents a unique opportunity to emerge stronger from the pandemic and achieve long-term impact.
References:
[1] Public Law 116 -139—Paycheck Protection Program and Health Care Enhancement Act.
[2] NIH mobilizes national innovation initiative for COVID-19 diagnostics, NIH news release, April 29, 2020.
[3] Rapid scaling up of Covid-19 diagnostic testing in the United States—The NIH RADx Initiative. Tromberg BJ, Schwetz TA, Pérez-Stable EJ, Hodes RJ, Woychik RP, Bright RA, Fleurence RL, Collins FS. N Engl J Med. 2020 Sep 10;383(11):1071-1077.
[4] We need more covid-19 tests. We propose a ‘shark tank’ to get us there. Alexander L. and Blunt R., Washington Post, April 20, 2020.
[5] RADx® Tech/ATP dashboard, National Institute of Biomedical Imaging and Bioengineering, NIH.
[6] New HHS actions add to Biden Administration efforts to increase access to easy-to-use over-the-counter COVID-19 tests. U.S. Department of Health and Human Services Press Office, October 25, 2021.
[7] A method for variant agnostic detection of SARS-CoV-2, rapid monitoring of circulating variants, detection of mutations of biological significance, and early detection of emergent variants such as Omicron. Lai E, et al. medRxiV preprint, January 9, 2022.
[9] Longitudinal assessment of diagnostic test performance over the course of acute SARS-CoV-2 infection. Smith RL, et al. J Infect Dis. 2021 Sep 17;224(6):976-982.
[10] Comparison of rapid antigen tests’ performance between Delta (B.1.61.7; AY.X) and Omicron (B.1.1.529; BA1) variants of SARS-CoV-2: Secondary analysis from a serial home self-testing study. Soni A, et al. MedRxiv preprint, March 2, 2022.
[11] Reporting COVID-19 self-test results: The next frontier. Health Affairs, Juluru K., et al. Health Affairs, February 11, 2022.
[12] Radical solutions. Nat Biotechnol. 2021 Apr;39(4):391.
Links:
Get Free At-Home COVID Tests (COVID.gov)
When to Test (Consortia for Improving Medicine with Innovation & Technology, Boston)
RADx Programs (NIH)
RADx® Tech and ATP Programs (National Institute of Biomedical Imaging and Biomedical Engineering/NIH)
Independent Test Assessment Program (NIBIB)
Mobile Application Reporting through Standards (NIBIB)
Point-of-Care Technologies Research Network (POCTRN) (NIBIB)
[Note: Acting NIH Director Lawrence Tabak has asked the heads of NIH’s Institutes and Centers (ICs) to contribute occasional guest posts to the blog to highlight some of the interesting science that they support and conduct. This is the eighth in the series of NIH IC guest posts that will run until a new permanent NIH director is in place.]
Racing to Develop Fast, Affordable, Accessible Tests for COVID-19
Posted on by Dr. Francis Collins
Developing faster, more convenient ways of testing for coronavirus disease 2019 (COVID-19) will be essential to our efforts to end this deadly pandemic. Despite the tremendous strides that have been made in diagnostics over the past seven months, we still need more innovation.
We need reliable, affordable tests for the presence SARS-CoV-2—the novel coronavirus that causes COVID-19—that do not take hours or days to deliver results. We need tests that are more user friendly, and that don’t rely on samples collected by swabs that have to be inserted deep into the nose by someone wearing PPE. We need tests that can be performed at the point-of-care, whether a doctor’s office, urgent care clinic, long-term care facility, or even a home. Ideally, such tests should also be able to integrate with mobile devices to convey results and transmit data seamlessly. Above all, we need tests that are accessible to everyone.
Most current diagnostic tests for SARS-CoV-2 involve detecting viral genetic material using a decades-old technology called the polymerase chain reaction (PCR). If there’s even a tiny bit of viral genetic material in a patient’s sample, PCR can amplify the material millions of times so that it can be readily detected. The problem is that this amplification process is time-consuming and requires a thermal cycling machine that’s generally operated by trained personnel in sophisticated lab settings.
To spur the creation of new approaches that can rapidly expand access to testing, NIH launched the Rapid Acceleration of Diagnostics (RADx) program in late April 2020. This fast-paced, innovative effort, conducted in partnership with the Office of the Assistant Secretary of Health, the Biomedical Advanced Research and Development Authority (BARDA), and the Department of Defense, is supported by $1.5 billion in federal stimulus funding. The goal? To expand diagnostic testing capacity for COVID-19 in the United States to about 6 million tests per day by December. That’s quite a leap forward because our nation’s current testing capacity is currently about 1 million tests per day.
Just yesterday, I joined other NIH leaders in authoring a special report in the New England Journal of Medicine that describes RADx’s main activities, and provides an update on the remarkable progress that’s been made in just three short months [1]. In a nutshell, RADx consists of four components: RADx-tech, RADx Advanced Technology Platforms (RADx-ATP). RADx Radical (RADx-rad), and RADx Underserved Populations (RADx-UP).
Though all parts of RADx are operating on a fast-track, RADx-tech has embraced its rapid timelines in a can-do manner unlike anything that I’ve encountered in my 27 years in government. Here’s how the process, which has been likened to a scientific “shark tank,” works.
Once an applicant submits a test idea to RADx-tech, it’s reviewed within a day by a panel of 30 experts. If approved, the application moves to a highly competitive “shark-tank” in which a team of experts spend about 150 to 200 person-hours with the applicant evaluating the technical, clinical, and commercial strengths and weaknesses of the proposed test.
From there, a detailed proposal is presented to a steering committee, and then sent to NIH. If we at NIH think it’s a great idea, promising early-stage technologies enter what’s called “phase one” development, with considerable financial support and the expectation that the applicant will hit its validation milestones within a month. Technologies that succeed can then go to “phase two”, where support is provided for scale-up of tests for meeting regulatory requirements and supporting manufacture, scale-up, and distribution.
The major focus of RADx-tech is to simplify and speed diagnostic testing for COVID-19. Tests now under development include a variety of mobile devices that can be used at a doctor’s office or other point-of-care settings, and give results in less than an hour. In addition, about half of the tests now under development use saliva or another alternative to samples gathered via nasal swabs.
As Americans think about how to move back safely into schools, workspaces, and other public areas in the era of COVID-19, it is clear that we need to figure out ways to make it easier for everyone to get tested. To attain that goal, RADx has three other components that build on different aspects of this social imperative:
• RADx Advanced Technology Platforms (RADx-ATP). This program offers a rapid-response application process for firms with existing point-of-care technologies authorized by the Food and Drug Administration (FDA) for detecting SARS-CoV-2. These technologies are already advanced enough that they don’t need the shark tank. The RADx-ATP program provides support for scaling up production to between 20,000 and 100,000 tests per day by the fall. Another component of this program provides support for expanding automated “mega-labs” to increase testing capacity across the country by another 100,000 to 250,000 tests per day.
• RADx Radical (RADx-rad). The program seeks to fuel the development of truly futuristic testing technologies. For example, it supports projects that use biomarkers to detect an infection or predict the severity of disease, including the likelihood of developing COVID-related multisystem inflammatory syndrome in children (MIS-C). Other areas of interest include the use of biosensors to detect the presence of the virus in a person’s breath and the analysis of wastewater to conduct community-based surveillance.
• RADx Underserved Populations (RADx-UP). Data collected over the past several months make it clear that Blacks, Latinxs, and American Indians/Alaska Natives are hospitalized and die of COVID-19 at disproportionately higher rates than other groups. RADx-UP aims to engage underserved communities to improve access to testing. Such actions will include closely examining the factors that have led to the disproportionate burden of the pandemic on underserved populations, as well as building infrastructure that can be leveraged to provide optimal access and uptake of SARS-CoV-2 testing in such communities.
At NIH, we have great hopes for what RADx-supported research will do to help bring to an end the greatest public health crisis of our generation. Yet the benefits may not end there. The diagnostic testing technologies developed here will have many other applications moving forward. Long after the COVID-19 pandemic becomes a chapter in history books, I’m convinced the RADx model of rapid innovation will be inspiring future generations of researchers as they look for creative new ways to address other diseases and conditions.
Reference:
[1] Rapid scaling up of COVID-19 diagnostic testing in the United States—The NIH RADx Initiative. Tromberg BJ, Schwetz TA, Perez-Stable E, Hodes RJ. Woychick RP, Bright RA, Fleurence RL, Collins FS. NEJM; 2020 July 16. [Online publication ahead of print]
Links:
Coronavirus (COVID-19) (NIH)
Rapid Acceleration of Diagnostics (RADx)
“NIH mobilizes national innovation initiative for COVID-19 diagnostics,” NIH news release, April 29, 2020.
Rising to the COVID-19 Challenge: Rapid Acceleration of Diagnostics (RADx)
Posted on by Dr. Francis Collins
Step into any major medical center, and you will see the amazing power of technology at work. From X-rays to functional MRIs, blood typing to DNA sequencing, heart-lung machines to robotic surgery, the progress that biomedical technology has made over the past century or so stands as a testament to human ingenuity—and its ability to rise to the all-important challenge of saving lives and improving health.
Today, our nation is in the midst of trying to contain a most formidable health threat: the global coronavirus disease 2019 (COVID-19) pandemic. I’m convinced that biomedical technology has a vital role to play in this urgent effort, which is why the NIH today launched the Rapid Acceleration of Diagnostics (RADx) Initiative.
Fueled by a bold $1.5 billion investment made possible by federal stimulus funding, RADx is an urgent call for science and engineering’s most inventive and visionary minds—from the basement to the board room—to develop rapid, easy-to-use testing technologies for SARS-CoV-2, the novel coronavirus that causes COVID-19. To achieve this, NIH will work closely with our colleagues at the Biomedical Advanced Research and Development Authority, the Centers for Disease Control and Prevention, and the Food and Drug Administration.
If all goes well, RADx aims to support innovative technologies that will make millions more rapid SARS-CoV-2 tests available to Americans by late summer or fall. Such widespread testing, which will facilitate the speedy identification and quarantine of infected individuals and their contacts, will likely be a critical component of making it possible for Americans to get safely back into public spaces, including returning to work and school.
For history buffs and tech geeks, the RADx acronym might ring a bell. During the World War II era, it was the brainstorming of MIT’s “Rad Lab” that gave birth to radar—a groundbreaking technology that, for the first time, enabled humans to use radio waves to “see” planes, storm systems, and many other things. Radar played such a valuable role in finding bombing targets, directing gunfire, and locating enemy aircraft, ships, and artillery that some have argued that this technology actually won the war for the U.S. and its Allies.
As for NIH’s RADx, our aim is to speed the development and commercialization of tests that can rapidly “see” if people have been infected with SARS-CoV-2 with very high sensitivity and specificity, meaning there would be few false negatives and false positives. A key part of this effort, which started today, will be a national technology development competition that’s open to all comers. In this competition, which begins a bit like a “shark tank,” participants will vie for an ultimate share of an approximately $500 million fund that will be awarded to help advance the most-promising testing technologies.
The proposals will undergo an initial review for technical, clinical, commercial, and regulatory issues. For example, could the testing technology be easily scaled up? Would it provide clear advantages over existing approaches? And would the U.S. health-care system realistically be able to adopt the technology rapidly? If selected, the proposals will then enter a three-phase process that will run into summer. Each development team will receive its own initial budget, deadlines, and set of deliverables. Competitors must also work collaboratively with an assigned expert and utilize associated web-based tools.
As you see in the graphic above, each phase will whittle down the competition. Those testing technologies that succeed in making it to Phase 2 will receive an appropriate budget to enable full clinical deployment on an accelerated timeline. They will also be matched with technical, business, and manufacturing experts to boost their chances of success.
Of course, not all technologies will enter the competition at the same stages of development. Those that are already relatively far along will be “fast tracked” to a phase that corresponds with their place in the commercialization process. Our hope is that the winning technologies will feature patient- and user-friendly designs, mobile-device integration, affordable cost, and increased accessibility, for use at the point of care (or even at home).
To assist competitors in their efforts to accomplish these bold goals, RADx will expand the Point-of-Care Technologies Research Network, which was established several years ago by NIH’s National Institute of Biomedical Imaging and Bioengineering (NIBIB). The network supports hundreds of investigators through five technology hubs at: Emory University/Georgia Institute of Technology, Atlanta; Johns Hopkins University, Baltimore; Northwestern University, Evanston, IL; University of Massachusetts Medical School, Worcester; and the Consortia for Improving Medicine with Innovation & Technology at Harvard Medical School/Massachusetts General Hospital, Boston.
RADx is focused on diagnostic testing, but NIH is also intensely engaged in developing safe, effective therapies and vaccines for COVID-19. One innovative effort, called Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV), is a public-private partnership that aims to speed the development of ways to treat and prevent this disease that’s caused so much suffering and death around the globe.
So, to the U.S. science and engineering community, I have these words: Let’s get going—our nation has never needed your skills more!
Links:
Coronavirus (COVID-19) (NIH)
NIH mobilizes national innovation initiative for COVID-19 diagnostics, NIH news release, April 29, 2020
Point-of-Care Technologies Research Network (National Institute of Biomedical Imaging and Biotechnology/NIH)
NIH to launch public-private partnership to speed COVID-19 vaccine and treatment options, NIH news release, April 17, 2020.
We Need More COVID-19 Tests. We Propose a ‘Shark Tank’ to Get There, Lamar Alexander, Roy Blunt. Washington Post, April 20, 2020.
