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 . 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.
 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]
Coronavirus (COVID-19) (NIH)
Rapid Acceleration of Diagnostics (RADx)
“NIH mobilizes national innovation initiative for COVID-19 diagnostics,” NIH news release, April 29, 2020.
Insurance Status Helps Explain Racial Disparities in Cancer Diagnosis
Posted on by Dr. Francis Collins
Women have the best odds of surviving breast cancer if their disease is caught at an early stage, when treatments are most likely to succeed. Major strides have been made in the early detection of breast cancer in recent years. But not all populations have benefited equally, with racial and ethnic minorities still more likely to be diagnosed with later-stage breast cancer than non-Hispanic whites. Given that recent observance of Martin Luther King Day, I thought that it would be particularly appropriate to address a leading example of health disparities.
A new NIH-funded study of more than 175,000 U.S. women diagnosed with breast cancer from 2010-2016 has found that nearly half of the troubling disparity in breast cancer detection can be traced to lack of adequate health insurance. The findings suggest that improving insurance coverage may help to increase early detection and thereby reduce the disproportionate number of breast cancer deaths among minority women.
Naomi Ko, Boston University School of Medicine, has had a long interest in understanding the cancer disparities she witnesses first-hand in her work as a medical oncologist. For the study published in JAMA Oncology, she teamed up with epidemiologist Gregory Calip, University of Illinois Cancer Center, Chicago . Their goal was to get beyond documenting disparities in breast cancer and take advantage of available data to begin to get at why such disparities exist and what to do about them.
Disparities in breast cancer outcomes surely stem from a complicated mix of factors, including socioeconomic factors, culture, diet, stress, environment, and biology. Ko and Calip focused their attention on insurance, thinking of it as a factor that society can collectively modify.
Many earlier studies had shown a link between insurance and cancer outcomes . It also stood to reason that broad differences among racial and ethnic minorities in their access to adequate insurance might drive some of the observed cancer disparities. But, Ko and Calip asked, just how big a factor was it?
To find out, they looked to the NIH’s Surveillance Epidemiology, and End Results (SEER) Program, run by the National Cancer Institute. The SEER Program is an authoritative source of information on cancer incidence and survival in the United States.
The researchers focused their attention on 177,075 women of various races and ethnicities, ages 40 to 64. All had been diagnosed with invasive stage I to III breast cancer between 2010 and 2016.
The researchers found that a higher proportion of women receiving Medicaid or who were uninsured received a diagnosis of advanced stage III breast cancer compared with women with health insurance. Black, American Indian, Alaskan Native, and Hispanic women also had higher odds of receiving a late-stage diagnosis.
Overall, their sophisticated statistical analyses traced up to 47 percent of the racial/ethnic differences in the risk of locally advanced disease to differences in health insurance. Such late-stage diagnoses and the more extensive treatment regimens that go with them are clearly devastating for women with breast cancer and their families. But, the researchers note, they’re also costly for society, due to lost productivity and escalating treatment costs by stage of breast cancer.
These researchers surely aren’t alone in recognizing the benefit of early detection. Last week, an independent panel convened by NIH called for enhanced research to assess and explore how to reduce health disparities that lead to unequal access to health care and clinical services that help prevent disease.
 Association of Insurance Status and Racial Disparities With the Detection of Early-Stage Breast Cancer. Ko NY, Hong S, Winn RA, Calip GS. JAMA Oncol. 2020 Jan 9.
 The relation between health insurance coverage and clinical outcomes among women with breast cancer. Ayanian JZ, Kohler BA, Abe T, Epstein AM. N Engl J Med. 1993 Jul 29;329(5):326-31.
 Cancer Stat Facts: Female Breast Cancer. National Cancer Institute Surveillance, Epidemiology, and End Results Program.
Cancer Disparities (National Cancer Institute/NIH)
Breast Cancer (National Cancer Institute/NIH)
Naomi Ko (Boston University)
Gregory Calip (University of Illinois Cancer Center, Chicago)
NIH Support: National Center for Advancing Translational Sciences; National Cancer Institute; National Institute on Minority Health and Health Disparities