By Jeffrey E. Shuren, MD, JD
Diagnostic tests are an important tool in anticipating and meeting the continuing and evolving public health needs as we combat covid-19. On June 16, 2020, the FDA took a meaningful step forward in getting more tests to more Americans more quickly and making that process even easier for developers by posting template updates regarding the validation of molecular diagnostic tests for developers that intend their assay to be used for pooling patient samples or for screening asymptomatic individuals not suspected of having covid-19.
The FDA has authorized molecular diagnostic tests for individuals suspected of having covid-19 by their healthcare provider. Such individuals can be symptomatic, presymptomatic, or asymptomatic. It has always been a healthcare provider’s discretion to test asymptomatic individuals when warranted. Using covid-19 diagnostic tests in this way is not the same as using such tests as a broad screening tool.
FDA has outlined the steps for a test to be authorized for broad screening of asymptomatic individuals by publicly providing information in updated templates for test developers on the FDA’s expectations for how a test can be validated for screening of asymptomatic individuals. This will make it easier for developers to get their tests authorized for this use. The FDA recognizes that organizations may want to conduct screening of asymptomatic individuals as part of a broader strategy to help ensure the safety of their employees, patients, students and others. In addition to these template updates, the FDA has made available FAQs with information regarding tests for screening asymptomatic individuals.
In order to preserve testing resources, many developers are interested in performing their testing using a technique of “pooling” samples. This technique allows a lab to mix several samples together in a “batch” or pooled sample and then test the pooled sample with a diagnostic test. For example, four samples may be tested together, using only the resources needed for a single test. If the pooled sample is negative, it can be deduced that all patients were negative. If the pooled sample comes back positive, then each sample needs to be tested individually to find out which was positive. Because samples are pooled together, ultimately fewer tests are run overall, meaning fewer testing supplies are used, and results can be returned to patients more quickly in most cases. However, because samples are diluted, which could result in less viral genetic material available to detect, there is a greater likelihood of false negative results, particularly if not properly validated. This method works well when there is a low prevalence of cases, meaning more negative results are expected. Given that testing asymptomatic individuals means testing a greater volume of patients, and a low prevalence may be more likely in an asymptomatic population, particularly if the population is at low risk for contracting covid-19, developers may be interested in using pooling techniques in tests used for asymptomatic screening.
The FDA has always been open to working with diagnostic developers on novel testing ideas, like asymptomatic screening and specimen pooling, and has encouraged all test developers to reach out to discuss appropriate validation approaches. Today, the FDA is taking another step forward by updating templates for test developers that outline the validation expectations for these testing options to help facilitate the preparation, submission, and authorization under an emergency use authorization (EUA).
The steps taken today by the FDA further demonstrate how we are proactively working with diagnostic test developers to facilitate new approaches and get more tests to more Americans more quickly.
Jeffrey E. Shuren, MD, JD, is the director FDA Center for Devices and Radiologic Health.
Featured image: Jeffrey E. Shuren, MD, JD, FDA. Photo courtesy FDA.