Pooled tests: what it is and how it can be used for coronavirus


It is not feasible to continually evaluate everyone in one complete test per person. There simply are not enough resources and supplies.

But the group tests, under the right circumstances, Ultimately, it may involve fewer tests and supplies, but it can encompass far more people than is being tested now.

“The grouping would give us the ability to go from half a million tests per day to potentially 5 million individuals examined per day,” Dr. Deborah Birx, a White House coronavirus workforce, told the American Society of Microbiology last month.

Preparations are underway. The United States Food and Drug Administration released a guide last month for developers who want to test and use pooled samples.

Here is a closer look:

How does the group test work?

In a basic level, this is group test:

Let’s say a laboratory has collected samples, such as those collected from nasal swabs, from five people. The laboratory will take a portion of each sample and mix them together, creating a group.

Now, one diagnostic test will be run on that pooled sample, instead of five diagnostic tests on five samples.

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“If the pooled sample is negative, it can be inferred that all patients were negative,” wrote Dr. Jeffrey Shuren, director of the FDA’s Center for Devices and Radiological Health, last month.

“If the pooled sample is positive, then each sample must be analyzed individually to determine which was positive.

“Because the samples are pooled, ultimately fewer tests are run overall, which means fewer test supplies are used.”

There is an important caveat: Basic group tests increase the chance of false negatives. Among the reasons: the samples are diluted in pools, so a true positive could be lost, according to Dr. Manisha Juthani, an associate professor of medicine and epidemiology at Yale School of Medicine.

Experts say there are ways to mitigate that risk, which we’ll explore later.

Is this for the general population, or for smaller groups, such as schools and factories?

Much will depend on circumstances, needs and imagination.

First, know this: Group testing should be done only where the prevalence of the disease is low, according to Eugene Litvak, an assistant professor of operations management at the Harvard University School of Public Health.

That is, group testing should be done where you would expect many negative results, and you’re only trying to spot the few cases that may exist, say Litvak and other experts.

To put it broadly, there is no point group testing somewhere that already has many cases, such as a nursing home with multiple positive patients. Virtually all groups would be positive; You could also have tried them all individually.

That said, there are plenty of places where group testing could make sense, according to Juthani and other experts:

Communities where Covid-19 is rare

“Large-scale pooled tests can be very cost-effective and save time to quickly identify positive cases, quarantine them, and follow up from there to prevent further spread of disease in a community,” Juthani, who is also a specialist in infectious diseases at Yale Medicine, he told CNN.

One scenario would be group testing in communities that have just had their first Covid-19 hospitalizations, Birx said in his June 22 speech at ASM.

The goal would be to find infected people, especially those who may be spreading the disease without showing symptoms, and isolate them before the spread worsens, Birx said.

Neighborhoods that need to be evaluated in an outbreak

In this scenario, an entire family could be part of a group, Juthani said.

Schools, universities and large employers.

Group testing could be a key tool for schools, organizations or workplaces that want to remain open safely, periodically monitoring their staff.

“If a one-bedroom wing, or a classroom in a school, is a pool and they are all tested together, that group could quickly clear up,” Juthani said.

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Litvak, who is also CEO of the nonprofit Institute for Healthcare Optimization near Boston, emphasized that group testing is useful only if it can be done in minutes rather than days.

That’s because if the days go by, it has potentially allowed an infected person to spread the disease while they wait.

The use of robotics in the labs is necessary, both for speed and for tracking pools and samples, Litvak told CNN.

Such robotics has been around for decades, Litvak said, adding that “he would be surprised if (capacity in the United States) is an issue.”

What is the history of group testing and where is it being done now?

Harvard economist Robert Dorfman developed group testing procedures to detect syphilis in American soldiers during World War II, Litvak said. Decades later, Litvak aided the research and author of group testing protocols for HIV.

Some countries have already been using group tests for the coronavirus pandemic.

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“If you look around the world, the way that people do a million tests or 10 million tests is that they are grouping,” Birx said last month.

In May, authorities in Wuhan, China conducted millions of tests in days, in part through pooled tests, Chinese news outlet Caixin reported.

Countries with limited resources with limited availability of tests and low disease prevalence, such as Rwanda, have also used group tests well, Juthani said.

How many samples of people could be in a group?

A recent study in Israel recently showed that, for Covid-19 group tests, one test could evaluate groups of at least 32 nasal samples without losing sensitivity or the ability to correctly identify true positives, Litvak said.

But U.S. health officials have generally been talking about groups of lower numbers. Birx has spoken of pools of five or more.

Generally speaking, the higher the prevalence of the disease in a population, the smaller their pools should be, Litvak said.

How does this work with less testing overall?

If a group test is positive, yes, you must evaluate everyone individually. Then, according to the basic procedure, you will have run one more test (the group test) than you would have, if you had decided to test each one individually from the start.

But, that’s why group testing should be done in populations where the disease is not believed to be widespread. Under those circumstances, you presumably eliminate many people with just one test.

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Juthani gives this example under the basic procedure: suppose you take 100 people and divide them into 20 groups of five. Now assume a prevalence rate of just 5%, which means there will be five true positives out of 100.

If each of the five positives appears in a separate group, five of its 20 groups are positive.

Therefore, he ran 20 group tests and, because of the group’s five positives, he also has to evaluate 25 people.

That’s 45 diagnostic tests, up from 100 diagnostic tests if you had evaluated each individual separately from the start.

It becomes inefficient if the prevalence rate is high. If there were 30 true positives in your group of 100, all of your 20 groups of five could have at least one positive sample. If all pools are positive, you have to run all the individual samples, so you have now run 120 tests (20 pools and 100 singles), which is a waste of time and resources.

How do you protect yourself against false negatives?

The FDA cautions, as noted above, that group tests could lead to more false negatives than simple individual tests if the results “are not properly validated.”

Pool samples could be analyzed twice, for added confidence, says Juthani.

In that situation, using one of the above scenarios, you can run (5% prevalence; 100 subjects; 20 group tests), you would have:

• 20 initial tests

• 15 to 20 confirmatory tests (because five should be positive at some point)

• 25 individual tests due to the five positive groups.

It would have passed 60 to 65 tests, even fewer than the 100 tests it would have done individually.

Other problems could lead to false negatives, including poor sample collection, or poor testing with low specificity, says Juthani.

Litvak advocates an even more rigorous approach, called a split group test. He said his research from the 1990s showed that this is dramatically more accurate than simple combined tests.

The divided group test is:

1) Try a group – say, it’s eight people – twice. If the group is negative twice, eliminate all.

2) If the group tests positive at any time, divide the group in half and then test both halves twice. In this example, create two groups of four and test each group twice.

3) Delete any group that was negative. If any group of four tests is positive, divide that group again, two groups of two, and repeat until you have individual tests.

This will still result in fewer tests than going directly to individual tests, assuming a low prevalence. And, because this protocol reduces the eventual number of individual tests required, it can even produce fewer tests than simple combined tests.

The divided group test should be the preferred protocol, he said.

“Given the urgent need for large-scale testing in the US and limited resources, the correct pooled testing protocol becomes a priority,” he said.

CNN’s Jacqueline Howard, Amanda Watts and Lauren Mascaren have contributed to this report.

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