False Positive Rates for COVID-19 Diagnostics Could Have Dire Unintended Consequences When Used for Screening in Certain Populations
Those Working to Establish Back to School and Back to Work Testing Strategies Should Consider the Quality of the Information Provided by the Diagnostics They Use
On September 16, 2020, the U.S. Food & Drug Administration (FDA) held its weekly town hall-style meeting where the in vitro diagnostics (IVD) community was invited to ask clarifying questions about the emergency use authorization (EUA) process for SARS-CoV-2 diagnostic tests.
The key takeaways are listed below:
- Developers following Pathway A can now choose whether or not they are added to the notification list. Pathway A is intended for laboratories CLIA certified as high-complexity who seek to develop and perform diagnostic tests. After notifying the FDA of intent to market, the laboratories following Pathway A will have 15 business days to submit their validation data to the FDA and may remain on the market during that time.
- False positives have not received as much attention as false negatives when considering the potential errors of diagnostic tests, but the unintended consequences of false positives are important when considering scenarios such as screening. The FDA presented the following hypothetical scenario to illustrate the point. If a test with 95% sensitivity and 99% specificity were used in a population with a 0.2% positive prevalence rate, the positive predictive value for that test is calculated to be 16%. That means roughly one in six positive test results are actually real and indicate infection with SARS-CoV-2. Consider if these results were used to decide which patients enter the COVID-19 ward of a hospital. Patients who were not ill could be sequestered unnecessarily and end up becoming infected. While screening tools are important and have their role, the best practice is to send samples from patients flagged as positive for confirmatory testing using high-sensitivity molecular assays.
- The FDA has released the first SARS reference panel testing results. This resource details the limits of detection (LODs) for samples that use transport media, samples that use dry swabs, and saliva samples in three different tables. Comparisons between tests listed on the same table are possible, but comparisons between tests on different tables are discouraged due to the different methodologies used to determine the LOD levels reported in each table.
- The FDA is routinely updating its FAQ page on diagnostic testing for SARS-CoV-2, which can be found here: https://www.fda.gov/medical-devices/emergency-situations-medical-devices/faqs-diagnostic-testing-sars-cov-2
- A full recording of the meeting can be found here: https://www.fda.gov/medical-devices/workshops-conferences-medical-devices/virtual-town-hall-series-immediately-effect-guidance-coronavirus-covid-19-diagnostic-tests-07012020
- Use the MedWatch system to report any suspected issues with COVID-19 IVD tests, found here: https://www.fda.gov/safety/medwatch-fda-safety-information-and-adverse-event-reporting-program
How Can Exponent Help
Exponent’s multi-disciplinary team of in vitro diagnostic, medical device, and pharmaceutical industry professionals develops safety information for products and processes that comply with pertinent standards, regulations, and best practices. With expertise in CLIA compliance, quality system establishment, and FDA assessments, Exponent can assist in reviewing submission packages, auditing labs, or performing due diligence and can assist with aspects of technical design, verification, and validation of the assay, instrument, or collection kit. Our offerings also include reviewing diagnostic data to assess the completeness of the package for submission according to any of the EUA pathways.
The FDA held town hall-style meetings for the in vitro diagnostics community to ask questions to clarify the FDA's recently issued guidance for developing diagnostic tests for SAR-CoV-2. To read more on the key takeaways from each meeting and how Exponent can help, please see the links below:
September 22, 2020 - FDA Announces Developers Submitting EUA Applications are Not Guaranteed Placement for Screening Test Authorization
July 27, 2020 - FDA in Need of Data, Warns Against Using Tests/Test Materials in Unintended Ways
July 9, 2020 - FDA Continues to Fight Back Against Under-Performing COVID-19 Diagnostic Assays
July 9, 2020 - Supply Shortages Spark New Concerns as the FDA Receives Record Numbers of In Vitro Diagnostic EUA Applications
June 1, 2020 - Accuracy Issues Still Plague Developers While FDA Looks to At-Home Testing
June 1, 2020 - FDA Publishes List of Developers Who Can No Longer Legally Market Their COVID Test
May 18, 2020 - FDA Focusing on Accuracy for In Vitro Diagnostics for COVID-19
May 5, 2020 - FDA Holds Third Town Hall Meeting to Clarify Emergency COVID-19 Diagnostics Development Guidance
April 30, 2020 - FDA Discusses First Authorized Home Collection Kit
April 17, 2020 - FDA Holds Second Town Hall Meeting to Clarify Emergency COVID-19 Diagnostics Development Guidance
April 13, 2020 - FDA Holds Town Meetings to Clarify Recent COVID-19 Diagnostics Development Guidance
April 13, 2020 - FDA Releases Updated Guidance on Diagnostics Testing as Response to COVID-19 Crisis