CEO SUMMARY: Pooled testing for COVID-19 could be a double-edged sword for clinical labs and in vitro diagnostics companies. Offering the advantage of reducing the number of standard tests for SARS-CoV-2, this testing method would cut lab spending on tests and testing supplies, while conserving standard non-pooled tests for symptomatic patients. But pooled testing also could cut into test manufacturers’ revenue, a factor that could cause IVD firms not to adapt their FDA-issued authorizations to allow use of their assays for pooled testing.
TO INCREASE THE CAPACITY OF TESTING FOR THE NOVEL CORONAVIRUS, federal officials are recommendingthat clinical laboratories adopt a decades-old strategy called pooled testing.
This method of testing would help make the available number of COVID-19 tests go further, but widespread adoption of pooled testing changes the economics in different ways for COVID-19 test manufacturers and the clinical labs running those tests. As a result, pooled tests come with at least two pitfalls, according to a respected clinical pathologist and researcher.
The first pitfall is that pooled testing works best in areas of low virus prevalence, said Steven H. Hinrichs, MD, Chair of the Department of Pathology and Microbiology at the University of Nebraska Medical Center (UNMC). As of the second week in July, the prevalence of COVID-19 infections was rising in at least 37 states. Areas of low prevalence exist in all 50 states, but as infections spread, the number of low-prevalence areas decreases.
“For pooled testing, the ideal level of low prevalence would be an infection rate below 10%,” Hinrichs reported. Many states have infection rates above 15%, according to published reports.
The second pitfall about pooled testing is that test manufacturers may not be inclined to modify the emergency use authorizations (EUAs) that the FDA issued for manufacturers’ tests to allow for pooling because doing so might reduce standard testing and thus could cut into the test-makers’ revenue, Hinrichs noted.
“For COVID-19 test manufacturers, pooled testing has the potential to reduce the number of standard tests labs run by roughly 40% to 60%, depending on the population being tested,” explained Hinrichs. “Cutting the number of COVID-19 tests would be a disadvantage for test manufacturers because pooled tests would identify large numbers of uninfected individuals who would not require standard testing with EUA tests.
“On the other hand, this policy would be a significant advantage for U.S. labs because pooled testing would cut the number of standard tests,” he continued. “Clinical labs would save money on tests, reagents, and other supplies. It would also ease the burden on the lab’s technical staff.”
A Theory with Merit
In an interview with The Dark Report, Hinrichs allowed that the theory behind pooled testing has advantages in a pandemic. Under this theory, clinical labs would collect specimens from hundreds of individuals and pool samples together in defined batches. The ideal number of samples to pool appears to be five, although it’s possible to pool more than five in each batch, said Hinrichs.
Hinrichs and colleagues from UNMC and the University of Nebraska-Lincoln conducted research showing that five is the ideal number to batch in a COVID-19 testing pool. Their research was published in an article, “Assessment of Specimen Pooling to Conserve SARS CoV-2 Testing Resources,” on April 18 in the American Journal of Clinical Pathology (AJCP), Volume 153, Issue 6, June 2020, pages 715–718.
The objective of the research was to establish the optimal parameters for group testing of pooled specimens for the detection of SARS-CoV-2, the researchers wrote. “The most efficient pool size was determined to be five specimens,” they added. (See sidebar, “In Published Research, Scientists Describe a Proof of Concept for Pooled Testing,” below.)
Federal officials promoting the pooled-testing strategy may need to answer the question of how to get test manufacturers to adapt their EUA-allowed tests for pooled testing, Hinrichs said. Each test manufacturer with an EUA for a molecular test for SARS-CoV-2 would need to adapt their assays for pooling and apply to the FDA for a revised or bridged EUA, he noted. Some manufacturers may be reluctant to do so.
“We can pick a company that has an EUA from the FDA for a coronavirus test to serve as an example,” he said. “Speaking hypothetically, let’s say the company is Roche. They have a great essay for their cobas instrument. Would they be motivated to develop a pooling strategy? This is the question every test manufacturer will need to answer.
“The reason test manufacturers would not be motivated is that with pooled tests, they will lose test revenue because clinical labs would use fewer of their authorized tests,” Hinrichs explained. “Instead, they will gain some revenue from pooled testing, but not as much as they get now from their standard tests or as much as they would get if pooled testing is not introduced.
Revenue Decline Predicted
“The reason revenue from the sale of COVID-19 tests would decline is that our research shows—and we know from our experience—that pooled testing could help labs save between 40% and 60% of their reagent costs,” he noted. “That’s good for us as consumers and as laboratory directors.
“But it may not be good for manufacturers,” commented Hinrichs, a principal investigator for research that led to multiple national awards from the Association of Public Health Laboratories and two federal agencies, the Centers for Disease Control and Prevention (CDC) and the Department of Defense.
For clinical labs considering this strategy, it’s important to note that pooled testing works best in areas of low virus presence and is less effective in areas of high prevalence. “In our study, we show that it’s reasonable to pool five samples, although we realized that some people may want to pool 10 samples at once,” noted Hinrichs. “But even if one sample is positive in a pool of five, then testing five samples at once saves 80% of our costs if all of those samples are negative.
“But, if one sample is positive, each of those five samples needs to be retested using the standard test,” he explained. “That’s when a lab’s costs start to rise.” Costs increase because clinical labs need to run six tests: one test for the pooled sample and five more tests to identify each possible positive result.
In a low-risk area, fewer pools will turn positive. “This is why pooled testing works best when a COVID-19 test program is working in what we would call a low-risk population. By that I mean a low-prevalence area,” noted Hinrichs. “If the testing is for a high-risk population, then more of those pools will turn positive,” Hinrichs reported. “When they turn positive, the lab must test each member in the pool individually to identify which ones are positive.
“This is why my colleagues and I added a statistician when developing the research study published in AJCP. We wanted to ensure that all the math was done correctly to identify the ideal number of specimens, and how changing that number affects the number of specimens that need to be retested,” he commented.
“We know that each sample in a pool with positive results needs to be retested, but that not all of the positives in the pool will be positive with retesting,” he added. “Those samples in the pool that are truly negative will in fact be negative and the rest will be positive.
“We found that the ideal pool size does not save 80% of testing,” Hinrichs noted. “Depending on the prevalence of disease in the population, the savings are between 40% to 60%.”
In Published Research, Scientists Describe a Proof-of-Concept for COVID-19 Pooled Testing
IN A STUDY IN THE AMERICAN JOURNAL OF CLINICAL PATHOLOGY PUBLISHED IN APRIL, researchers from the University of Nebraska Medical Center and the University of Nebraska-Lincoln described a proof-of-concept for testing pooled specimens for the detection of SARS-CoV-2 in a population.
To test for COVID-19 successfully with a pooled method, clinical labs would need to know at least the following:
• The limit-of-detection for the assay involved,
• The sensitivity and specificity levels of the assay, and
• The prevalence of disease in the population being studied.
The goals of the research were to establish the optimal parameters for group testing of pooled specimens and to determine a pool size that provides the greatest conservation of resources while maintaining reliable test performance.
The researchers concluded that the most efficient size of each group of pooled tests was five specimens. Also, when the infection rate in a population is 10% or less, then pooled testing would be useful for screening large numbers of individuals to identify those who are infected and those who are not.
“When the incidence rate of SARSCoV-2 infection is 10% or less, group testing will result in the saving of reagents and personnel time with an overall increase in testing capability of at least 69%,” they wrote.
For many years, group testing of pooled samples has been used successfully for infectious disease testing and when hospitals and other entities are procuring blood, the researchers explained.
Contact Steven H. Hinrichs, MD, at 402-559-7255 or firstname.lastname@example.org.