NIBIB
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.]
Giving Thanks for Biomedical Research
Posted on by Dr. Francis Collins
This Thanksgiving, Americans have an abundance of reasons to be grateful—loving family and good food often come to mind. Here’s one more to add to the list: exciting progress in biomedical research. To check out some of that progress, I encourage you to watch this short video, produced by NIH’s National Institute of Biomedical Imaging and Engineering (NIBIB), that showcases a few cool gadgets and devices now under development.
Among the technological innovations is a wearable ultrasound patch for monitoring blood pressure [1]. The patch was developed by a research team led by Sheng Xu and Chonghe Wang, University of California San Diego, La Jolla. When this small patch is worn on the neck, it measures blood pressure in the central arteries and veins by emitting continuous ultrasound waves.
Other great technologies featured in the video include:
• Laser-Powered Glucose Meter. Peter So and Jeon Woong Kang, researchers at Massachusetts Institute of Technology (MIT), Cambridge, and their collaborators at MIT and University of Missouri, Columbia have developed a laser-powered device that measures glucose through the skin [2]. They report that this device potentially could provide accurate, continuous glucose monitoring for people with diabetes without the painful finger pricks.
• 15-Second Breast Scanner. Lihong Wang, a researcher at California Institute of Technology, Pasadena, and colleagues have combined laser light and sound waves to create a rapid, noninvasive, painless breast scan. It can be performed while a woman rests comfortably on a table without the radiation or compression of a standard mammogram [3].
• White Blood Cell Counter. Carlos Castro-Gonzalez, then a postdoc at Massachusetts Institute of Technology, Cambridge, and colleagues developed a portable, non-invasive home monitor to count white blood cells as they pass through capillaries inside a finger [4]. The test, which takes about 1 minute, can be carried out at home, and will help those undergoing chemotherapy to determine whether their white cell count has dropped too low for the next dose, avoiding risk for treatment-compromising infections.
• Neural-Enabled Prosthetic Hand (NEPH). Ranu Jung, a researcher at Florida International University, Miami, and colleagues have developed a prosthetic hand that restores a sense of touch, grip, and finger control for amputees [5]. NEPH is a fully implantable, wirelessly controlled system that directly stimulates nerves. More than two years ago, the FDA approved a first-in-human trial of the NEPH system.
If you want to check out more taxpayer-supported innovations, take a look at NIBIB’s two previous videos from 2013 and 2018 As always, let me offer thanks to you from the NIH family—and from all Americans who care about the future of their health—for your continued support. Happy Thanksgiving!
References:
[1] Monitoring of the central blood pressure waveform via a conformal ultrasonic device. Wang C, Li X, Hu H, Zhang, L, Huang Z, Lin M, Zhang Z, Yun Z, Huang B, Gong H, Bhaskaran S, Gu Y, Makihata M, Guo Y, Lei Y, Chen Y, Wang C, Li Y, Zhang T, Chen Z, Pisano AP, Zhang L, Zhou Q, Xu S. Nature Biomedical Engineering. September 2018, 687-695.
[2] Evaluation of accuracy dependence of Raman spectroscopic models on the ratio of calibration and validation points for non-invasive glucose sensing. Singh SP, Mukherjee S, Galindo LH, So PTC, Dasari RR, Khan UZ, Kannan R, Upendran A, Kang JW. Anal Bioanal Chem. 2018 Oct;410(25):6469-6475.
[3] Single-breath-hold photoacoustic computed tomography of the breast. Lin L, Hu P, Shi J, Appleton CM, Maslov K, Li L, Zhang R, Wang LV. Nat Commun. 2018 Jun 15;9(1):2352.
[4] Non-invasive detection of severe neutropenia in chemotherapy patients by optical imaging of nailfold microcirculation. Bourquard A, Pablo-Trinidad A, Butterworth I, Sánchez-Ferro Á, Cerrato C, Humala K, Fabra Urdiola M, Del Rio C, Valles B, Tucker-Schwartz JM, Lee ES, Vakoc BJ9, Padera TP, Ledesma-Carbayo MJ, Chen YB, Hochberg EP, Gray ML, Castro-González C. Sci Rep. 2018 Mar 28;8(1):5301.
[5] Enhancing Sensorimotor Integration Using a Neural Enabled Prosthetic Hand System
Links:
Sheng Xu Lab (University of California San Diego, La Jolla)
So Lab (Massachusetts Institute of Technology, Cambridge)
Lihong Wang (California Institute of Technology, Pasadena)
Video: Lihong Wang: Better Cancer Screenings
Carlos Castro-Gonzalez (Madrid-MIT M + Visión Consortium, Cambridge, MA)
Video: Carlos Castro-Gonzalez (YouTube)
Ranu Jung (Florida International University, Miami)
Video: New Prosthetic System Restores Sense of Touch (Florida International)
NIH Support: National Institute of Biomedical Imaging and Bioengineering; National Institute of Neurological Diseases and Stroke; National Heart, Lung, and Blood Institute; National Cancer Institute; Common Fund
New NIBIB Director
Posted on by Dr. Francis Collins
Seven More Awesome Technologies Made Possible by Your Tax Dollars
Posted on by Dr. Francis Collins
We live in a world energized by technological advances, from that new app on your smartphone to drones and self-driving cars. As you can see from this video, NIH-supported researchers are also major contributors, developing a wide range of amazing biomedical technologies that offer tremendous potential to improve our health.
Produced by the NIH’s National Institute of Biomedical Imaging and Bioengineering (NIBIB), this video starts by showcasing some cool fluorescent markers that are custom-designed to light up specific cells in the body. This technology is already helping surgeons see and remove tumor cells with greater precision in people with head and neck cancer [1]. Further down the road, it might also be used to light up nerves, which can be very difficult to see—and spare—during operations for cancer and other conditions.
Other great things to come include:
- A wearable tattoo that detects alcohol levels in perspiration and wirelessly transmits the information to a smartphone.
- Flexible coils that produce high quality images during magnetic resonance imaging (MRI) [2-3]. In the future, these individualized, screen-printed coils may improve the comfort and decrease the scan times of people undergoing MRI, especially infants and small children.
- A time-release capsule filled with a star-shaped polymer containing the anti-malarial drug ivermectin. The capsule slowly dissolves in the stomach over two weeks, with the goal of reducing the need for daily doses of ivermectin to prevent malaria infections in at-risk people [4].
- A new radiotracer to detect prostate cancer that has spread to other parts of the body. Early clinical trial results show the radiotracer, made up of carrier molecules bonded tightly to a radioactive atom, appears to be safe and effective [5].
- A new supercooling technique that promises to extend the time that organs donated for transplantation can remain viable outside the body [6-7]. For example, current technology can preserve donated livers outside the body for just 24 hours. In animal studies, this new technique quadruples that storage time to up to four days.
- A wearable skin patch with dissolvable microneedles capable of effectively delivering an influenza vaccine. This painless technology, which has produced promising early results in humans, may offer a simple, affordable alternative to needle-and-syringe immunization [8].
If you like what you see here, be sure to check out this previous NIH video that shows six more awesome biomedical technologies that your tax dollars are helping to create. So, let me extend a big thanks to you from those of us at NIH—and from all Americans who care about the future of their health—for your strong, continued support!
References:
[1] Image-guided surgery in cancer: A strategy to reduce incidence of positive surgical margins. Wiley Interdiscip Rev Syst Biol Med. 2018 Feb 23.
[2] Screen-printed flexible MRI receive coils. Corea JR, Flynn AM, Lechêne B, Scott G, Reed GD, Shin PJ, Lustig M, Arias AC. Nat Commun. 2016 Mar 10;7:10839.
[3] Printed Receive Coils with High Acoustic Transparency for Magnetic Resonance Guided Focused Ultrasound. Corea J, Ye P, Seo D, Butts-Pauly K, Arias AC, Lustig M. Sci Rep. 2018 Feb 21;8(1):3392.
[4] Oral, ultra-long-lasting drug delivery: Application toward malaria elimination goals. Bellinger AM, Jafari M1, Grant TM, Zhang S, Slater HC, Wenger EA, Mo S, Lee YL, Mazdiyasni H, Kogan L, Barman R, Cleveland C, Booth L, Bensel T, Minahan D, Hurowitz HM, Tai T, Daily J, Nikolic B, Wood L, Eckhoff PA, Langer R, Traverso G. Sci Transl Med. 2016 Nov 16;8(365):365ra157.
[5] Clinical Translation of a Dual Integrin avb3– and Gastrin-Releasing Peptide Receptor–Targeting PET Radiotracer, 68Ga-BBN-RGD. Zhang J, Niu G, Lang L, Li F, Fan X, Yan X, Yao S, Yan W, Huo L, Chen L, Li Z, Zhu Z, Chen X. J Nucl Med. 2017 Feb;58(2):228-234.
[6] Supercooling enables long-term transplantation survival following 4 days of liver preservation. Berendsen TA, Bruinsma BG, Puts CF, Saeidi N, Usta OB, Uygun BE, Izamis ML, Toner M, Yarmush ML, Uygun K. Nat Med. 2014 Jul;20(7):790-793.
[7] The promise of organ and tissue preservation to transform medicine. Giwa S, Lewis JK, Alvarez L, Langer R, Roth AE, et a. Nat Biotechnol. 2017 Jun 7;35(6):530-542.
[8] The safety, immunogenicity, and acceptability of inactivated influenza vaccine delivered by microneedle patch (TIV-MNP 2015): a randomised, partly blinded, placebo-controlled, phase 1 trial. Rouphael NG, Paine M, Mosley R, Henry S, McAllister DV, Kalluri H, Pewin W, Frew PM, Yu T, Thornburg NJ, Kabbani S, Lai L, Vassilieva EV, Skountzou I, Compans RW, Mulligan MJ, Prausnitz MR; TIV-MNP 2015 Study Group.
Links:
National Institute of Biomedical Imaging and Bioengineering (NIH)
Center for Wearable Sensors (University of California, San Diego)
Hyperpolarized MRI Technology Resource Center (University of California, San Francisco)
Center for Engineering in Medicine (Massachusetts General Hospital, Boston)
Center for Drug Design, Development and Delivery (Georgia Tech University, Atlanta)
NIH Support: National Institute of Biomedical Imaging and Bioengineering; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases
