First EUA for pooled COVID-19 test points to effect of prevalence on performance

FDA’s first authorization of a pooled COVID-19 test makes it clear this resource-saving approach is best reserved for populations where disease prevalence is low, highlighting the need to quickly adapt testing strategies in response to infection spikes.

The agency announced Saturday it granted Emergency Use Authorization (EUA) to Quest Diagnostics Inc. (NYSE:DGX) to use sample pooling with its reverse transcription polymerase chain reaction (RT-PCR)-based test, previously authorized for use on individual patient samples.

The test can be used on up to four individual upper respiratory swabs collected under observation from individuals suspected to have COVID-19 by their healthcare provider. A negative result for the pooled samples suggests all four individuals are negative for COVID-19; a positive result requires each sample in the pool to be re-tested individually.

The benefits of pooled testing are that it uses fewer resources per test and processes multiple samples at once, relieving pressure on the testing supply chain and returning results to patients more quickly. The strategy is routinely used to screen donated blood for a wide range of viruses.

Its limitations include a reduced ability to detect low viral concentrations due to the diluting effect of combining samples. That reduced sensitivity can increase the rate of false negatives, a risk that becomes more acute the more cases there are in the population (see “Good Test Hunting”).

In addition, the need to re-test every sample in a positive pool means the total number of tests run for that group of patients will be larger than if they had been tested individually; in populations where case prevalence is high, the toll of re-testing can negate the efficiencies of sample pooling.

Quest presented data to FDA indicating none of a total of 3,091 clinical samples from a population with a COVID-19 prevalence rate of 1-10% would have been incorrectly classified as COVID-19 negative. FDA said Quests’ validation data demonstrates its test correctly identified all sample pools that contained a positive sample.

The rapid rise of COVID-19 cases in hot spot areas means the calculus on pooled testing can change within a matter of weeks. For example, the seven day moving average of the percent of positive tests in the state of Arizona grew from around 10% in early June to over 23% in mid-July, according to Johns Hopkins University’s testing tracker.

Pooled testing’s higher throughput and better performance in populations with low case prevalence could make the strategy a good fit for broad screening of large asymptomatic populations.

On June 16, FDA updated its COVID-19 molecular diagnostic templates to include the agency’s expectations for test developers intending their assays to be used for sample pooling, and for asymptomatic screening.

While healthcare providers always have the discretion to test asymptomatic individuals, and testing is accessible to asymptomatic individuals via research studies, FDA has not yet authorized any test for the broad screening of asymptomatic individuals for COVID-19.

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