August 6, 2020
As the COVID-19 pandemic continues and communities across the U.S. face difficult decisions over restrictions on schools and businesses, screening will be a critical component in a safe and sustained reopening. While multiple in vitro diagnostic manufacturers have developed at-home kits that allow for sample collection without clinician oversight, COVID-19 tests currently remain prescription only.
A primary barrier to U.S. Food and Drug Administration (FDA) authorization for over-the-counter (OTC) use is the current lack of data to demonstrate that at-home users can perform tests correctly, accurately interpret positive or negative results, and comply with recommended actions. Ambiguity from false positive or false negative results presents an additional challenge. By providing data to demonstrate that OTC tests can mitigate these risks, developers of at-home COVID-19 screening tests can strengthen their applications under FDA's Emergency Use Authorization (EUA) program, potentially without a prescription-only status.
Demonstrating Ease of Test Administration
Ease of use is a key requirement for any FDA-authorized at-home test. With very limited exceptions, COVID-19 diagnostic and screening tests are currently performed in laboratories, hospitals, physicians' offices, and community testing facilities that can guarantee clinician oversight. These tests check samples to determine whether an individual is currently infected with SARS-CoV-2, the virus that causes COVID-19, typically using nasopharyngeal swabs for sample collection.
Unfortunately, this sample type is difficult to self-administer. Saliva and traditional nasal swab-collected samples may be easier to self-administer, but fewer high-sensitivity assay options are currently available for these types of samples. For in vitro diagnostic developers to bring at-home screening products to market, FDA will expect them to provide data from human factors assessments demonstrating that users can self-administer the tests in a way that leads to accurate sampling. To obtain such data, it will be imperative for developers to commission human factors studies that are carefully designed and use appropriate methodologies.
Accounting for Asymptomatic and Pre-Symptomatic Individuals
FDA recently highlighted a gap in study data on individuals who have tested positive for COVID-19 but who are asymptomatic or pre-symptomatic. This is partly because the Agency's templates for study design have historically focused on diagnostic tests for individuals suspected of having COVID-19, not screening tests for individuals without symptoms. Current tests can be used in the asymptomatic population at a physician's discretion, but such use underlines the importance of having a physician involved in interpreting the results. FDA plans to provide a template for study design of at-home screening tests in the near future, which will likely require developers to provide study data for test performance on asymptomatic and pre-symptomatic individuals.
Addressing False Test Results
Ambiguity from false positive or false negative test results presents an additional challenge for at-home screening developers. When drafting product labeling, it is important to consider how to minimize the risk that false results can pose to users and their communities. Labeling can remind users to protect themselves with social distancing, masks, and adherence to other CDC guidelines regardless of test result. It may also provide instructions designed to combat false negatives/positives, such as a dual-testing approach which would recommend the user take multiple tests spaced several days apart.
Navigating Reporting Obligations
Laboratories with a Clinical Laboratory Improvement Amendments (CLIA) certificate must report the results of the COVID-19 tests they conduct to the appropriate state or local public health department. If FDA removed the prescription status from a COVID-19 test, it would also remove the structure that allows this reporting obligation to be met. While product labeling may be one way for at-home test developers to help meet this obligation, labeling alone may not provide sufficient risk mitigation. Developers should engage FDA in a conversation about reporting obligations and reporting structure during pre-EUA discussions.
How Exponent Can Help
Exponent's multidisciplinary team of biomedical engineers, human factors scientists, and regulatory experts can help guide medical device manufacturers through the complete product development life cycle. We can help support assay design, clinical trial development, identification of user groups and representative samples, regulatory submission, technical and CLIA-based audits, and risk mitigation planning for at-home COVID-19 tests. Our human factors experts can also design and execute usability studies to identify potential use errors when individuals self-administer tests and perform comprehension studies to ensure that instructions for use and warning labels are easy to find, understand, and follow.