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In January 2020, the U.S. Food and Drug Administration (FDA) began to consider the U.S. response to Covid-19. On February 4, after announcing a public health emergency, we began authorizing tests to diagnose active infections. In such an emergency, the FDA can grant an emergency use authorization (EUA) for medical products based on the review of scientific evidence. Adopting lower EUA standards, rather than waiting for full approval to obtain broader evidence, can speed up the speed of obtaining accurate tests. After reporting asymptomatic cases, it is clear that we need to adopt other strategies to understand the true spread of SARS-CoV-2 across the country. During the previous virus outbreak, serological (i.e., antibody) testing has not been performed or has limited use. However, in this case, the FDA recognizes that ensuring rapid and adequate access to serological testing in the United States can promote scientific research and understanding of Covid-19, thereby helping to respond to the country.
Serological testing can detect the body’s adaptive immune response to past infections. Therefore, serological testing alone cannot determine whether a person is currently infected with SARS-CoV-2. In addition, although the experience of other viruses has shown that the presence of SARS-CoV-2 antibodies may confer some protection against reinfection, we do not know whether there are any antibodies? Or a certain level of antibodies? It means that a person has immunity to re-infection, and if so, how long will this immunity last?
In order to facilitate early access to serological testing by laboratories and healthcare providers, the FDA issued guidelines on March 16. The guidelines allow developers to promote their tests without the EUA. As long as the test passes the verification, they will be notified. FDA, and the test report contains important information about restrictions, including a statement that the test has not been reviewed by the FDA and the results cannot be used to diagnose or rule out infections. 1
At the time, serological testing was not usually used in patient care. We implement other protective measures by restricting its use to laboratories accredited by Medicare and Medicaid Services Centers to perform high-complexity testing in accordance with the Clinical Laboratory Improvement Amendment (CLIA). Such laboratories have personnel who specifically consider test performance and select the best test for a given purpose. Developer offices that intend to use serological tests at home or at the care site (e.g. doctors) (unless they are protected by the laboratory’s CLIA certificate) must still submit an EUA application and be authorized by the FDA for their testing. We plan to review this policy after several serological tests have been authorized. However, in hindsight, we realized that the policies outlined in our March 16 guidelines were flawed.
By the end of March, 37 commercial manufacturers had notified the FDA of their introduction of serological tests into the US market. The FDA received EUA’s request for serological testing and began authorizing the first test in April. However, in early April, government officials began touting the potential effects of these tests on the reopening of the economy and provided insurance for uses that are not supported by science and do not meet the limitations set by the FDA. As a result, the market is flooded with serological tests, some of which have poor results, and many are sold in ways that contradict FDA policies. By the end of April, 164 commercial manufacturers had notified the FDA that they had performed serological testing. This series of events is different from our experience in commercialized diagnostic tests. In this case, few tests are provided under notice; manufacturers usually promote their own tests instead of listing products made by other, usually non-US manufacturers, like certain serological tests; false claims and data There are far fewer cases of tampering.
On April 17, the FDA issued a letter to medical service providers explaining that some developers had abused the serological test kit notification list to falsely claim that their tests had been approved or authorized by the agency. 2 Although there are more than 200 serological testing reagent developers, the FDA has voluntarily submitted EUA or plans to submit EUA, so the FDA changed its policy on May 4 so that we can evaluate the scientific basis of all commercial distributed testing and evaluate its effectiveness Sex. 3 As of February 1, 2021, the FDA has cancelled the agreement. A list of 225 tests was listed from our website, 15 warning letters were issued, and import violation warnings were issued to 88 companies.
At the same time, since March, the FDA has been cooperating with the National Institutes of Health (NIH), the Centers for Disease Control and Prevention, and the Agency for Advanced Research and Development in Biomedicine to help the National Cancer Institute (NCI) establish the ability to evaluate serology. To help inform FDA’s regulatory decisions on individual tests (https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-publicly-shares-antibody-test-performance-data -kits-part-validation). The evaluation team assembled by NCI consists of 30 frozen SARS-CoV-2 antibody-positive serum samples and 80 frozen antibody-negative serum and anticoagulated citrate glucose solution formula A plasma samples. The size and composition of the panel were chosen to enable laboratory-based evaluation and to provide reasonable estimates and confidence intervals for test performance under limited sample availability. This work marks the first time the federal government has conducted a self-assessment to inform the FDA of authorization. Subsequently, the National Institutes of Health (NIH) used its relationship with the academic center to conduct preliminary evaluations of promising point-of-care points and home Covid-19 diagnostic tests under its RADx (Rapid Diagnostic Acceleration) program. 4
We have previously outlined our experience in Covid-19 diagnostic tests. 5 Relevant facts and participants-and FDA’s actions? The situation of serological examinations is also different, and the lessons we have learned are also different.
First, our experience in serological testing emphasizes the importance of independent authorization of medical products on a sound scientific basis, and does not allow unauthorized testing products to enter the market. Knowing what we now know, even without the restrictions we initially imposed, we would not allow serological testing without FDA review and authorization. Although other factors may cause a flood of unauthorized products into the market, our March 16 policy allows this to happen.
Second, as part of the outbreak plan, the federal government should coordinate the preparation of public-private research programs to address epidemiological issues related to disease transmission and immunity in the early stages of an outbreak. A concerted effort will help ensure that necessary research is conducted in a timely manner, minimize duplication of research, and make full use of federal resources.
Third, we should establish the ability to evaluate test performance within the federal government or on behalf of the federal government before the outbreak, so that independent evaluations can be carried out quickly during the outbreak. Our cooperation with NCI has shown us the value of this approach. Combined with FDA authorization, this strategy can allow rapid and independent evaluation of the accuracy of molecular diagnostics, antigen and serological tests, and minimize the need for developers to find patient specimens or other clinical samples to validate their tests, thereby accelerating The usability of accurate testing is improved. The federal government should also consider applying this method to technologies used outside of the epidemic. For example, NIH’s RADx program can continue and expand beyond Covid-19. In the long run, we need a common method to verify test design and performance.
Fourth, the scientific and medical community should understand the purpose and clinical use of serological testing, and how to use the test results appropriately to inform patient care in general. With the development of scientific knowledge, continuous education is essential in any public health emergency response, especially considering that serological testing methods are misused for diagnosis, and people with low infection rates may use a single testing method. There will be false positive results and perceived immunity to infection. Our testing methods need to be constantly updated and guided by reliable science.
Finally, all parties involved in the public health emergency response need to obtain better information faster. Just as medical experts are quickly trying to understand how Covid-19 affects patients and how to best treat patients, the FDA must adapt to limited and evolving information, especially in the early stages of an outbreak. The establishment of sound and coordinated national and international mechanisms to collect evidence and collect, share and disseminate information is essential for ending the current pandemic and responding to future public health emergencies.
Looking ahead, as the pandemic develops, the FDA will continue to take measures to ensure that accurate and reliable antibody tests are provided in a timely manner to meet public health needs.
1. Food and Drug Administration. The policy for diagnostic tests for the 2019 coronavirus disease in public health emergencies. March 16, 2020 (https://web.archive.org/web/20200410023229/https://www.fda.gov/media/135659/download).
2. Food and Drug Administration. Letter to healthcare providers about important information about the use of serology (antibodies) to detect COVID-19. April 17, 2020 (updated on June 19, 2020) (https://www.fda.gov/medical-devices/letters-health-care-providers/important-information-use-serological-antibody-tests- covid-19-letter to health care provider).
3. Shah A and ShurenJ. Learn more about the FDA’s revised antibody testing policy: Prioritize access and accuracy. Silver Spring, MD, Food and Drug Administration (FDA), May 4, 2020 (https://www.fda.gov/news-events/fda-voices/insight-fdas-revised-policy -antibody-tests-prioritizing-access-and -accuracy).
4. National Institutes of Health. Rapid Diagnostic Acceleration (RADx) (https://www.nih.gov/research-training/medical-research-initiatives/radx).
5. Shuren J, Stenzel T. Covid-19 molecular diagnostic test learned a lesson. The English Journal of Medicine 2020; 383(17): e97-e97.
Post time: Mar-10-2021