On False POSITIVES of rapid antigen tests.

This 🧵 is on SPECIFICITY or the issues of False POSITIVES and rapid antigen tests.

Many people are concerned that these fast, inexpensive tests cause too many false positives and will overload PCR labs...

Rapid antigen tests can have 98%-99.9% specificity meaning between 0.1% and 2% of tests run might be falsely positive.

If prevalence is low, even a 99.9% specificity could mean many of the positive tests are falsely positive.

But w rapid tests, there are rapid solutions!

Many ppl instinctively worry that a false positive will mean an erroneous 10 day isolation and that huge numbers of people are going to require laboratory based PCR confirmation tests and this will overload the system.

No, this is stuck-in-our-ways thinking...

With rapid tests, we don’t have to send in a PCR test for confirmation - it’s much simpler than that in a “rapid test world” - we can use a second rapid test... right there and have a confirmatory result in moments.

We do this all the time with HIV tests...

With HIV tests, if prevalence is low, ~50% of our positives may be false positive.

We don’t say the test is useless. We don’t make the person wait a week for a new test. We simply run the test on a second similar also imperfect test - combined they are very accurate.

W Rapid Ag tests, we can simply repeat the exact same test a second time. That will get rid of most false positives in five minutes.

Alternatively we just use two different rapid antigen tests. Every house has 10 yellow tests and 2 red confirmatory rapid tests...

If you turn positive on yellow test, use the red one. They look same but have different molecules. Will not be expected to turn falsely positive for the same reason.

This can get false positives to <1:2000 or, one false positive every few years if testing 2x /week.

In this same @CDCMMWR paper I’ve discussed, the authors found that each time they retested what turned out to be a false positive again w the exact same test, the test turned negative.

Within minutes ppl can know a positive is true or false.…

Therefore, we do not need need PCR tests and instead a massive rapid test program will ease the burden on PCR labs, NOT increase it.

We just have to take a step back and recognize there are simple solutions here.

Also - we can keep testing, hours later, or next day

The repeated convenient testing that rapid antigen tests afford not only GREATLY improve sensitivity over PCR (discussed elsewhere), but importantly increase specificity as well.

A false positive doesn’t mean automatic 10 day isolation when you can confirm at will.

That type of thinking is what happens when we only focus on lab based, slow, expensive Clinical diagnostic tests. For mass population screening, we have so many more options w rapid tests to improve sensitivity, specificity and massively improve EFFECTIVENESS of testing.

Also, last point - with a two test approach - we need to stop calling a single positive that doesn’t repeat, false.

We should consider the duo of tests as married. In that @CDCMMWR study above, they called them false positives even though they confirmed within minutes

Ideally, we should look at it as a testing algorithm. If both tests turn out to be the rare 2x false positive - THEN call it a false positive. Otherwise call it as it is - screening plus confirmation. We measure the program as the primary endpoint, not the individual parts.

If you’ve gotten this far an you are asking “but what about false negatives - I thought those are the major concern” yes. This was simply a thread about false positives.

I’ve written extensively about concern over false negatives as well.

Here’s one thread about it

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More from @michaelmina_lab

4 Jan
@apoorva_nyc @TakeWeightOffMD Seen a lot of responses talking about partial immunity here.

But, Unlike antibiotics, the comparison has to consider even greater “only partial immunity” among those who have had no vaccine by the time they get infected.

@apoorva_nyc @TakeWeightOffMD The immune response is going to develop whether you’ve been vaccinated or not. If you’ve had no vaccine, then there is going to be much more “only partial immunity” that the virus gets to play around with and “test out”

@apoorva_nyc @TakeWeightOffMD We have to very careful to not forget what the baseline is here. W antibiotics, the Bacteria is only exposed to a partial dose if youre on antibiotics. With immunity, the virus is exposed to a partial dose whenever you’re not already protected while immunity builds up.

Read 6 tweets
4 Jan

SO MUCH Continued CONFUSION about Rapid Antigen Tests - Now about Asymptomatics.

A New @CDC_gov @CDCMMWR study concludes Ag tests didn't work in Asymptomatic ppl. Simply put, It's wrong

Here I got in depth on Rapid Tests & how to evaluate them

The study found rapid Ag tests missed 40% of PCR +ve Asymptomatics.

BUT... FAILED to state that 100% of the misses were in ppl with NO CULTURABLE VIRUS (plus ALL had Ct values >30)

Rapid tests CAUGHT 100% of the infectious ppl!…

That's right!

In the very same study that concludes rapid Ag tests do not work in asymptomatic people, the authors failed to state the rapid Ag tests SUCCESSFULLY CAUGHT 100% of ASYMPTOMATIC PEOPLE who had likely contagious virus.

Read 31 tweets
3 Jan
Dear @CDCgov - Why can't you learn?

The paper concludes rapid Antigen tests had only 40% sensitivity in Asymptomatics

But failed to state they had 100% SENSITIVITY for what matters - culture +ve viable virus in Asymptomatics

PCR, not Ag, is wrong tool for Asymptomatic screens
The problem is simple

PCR remains +ve for long time after infectious

Meanwhile Ag tests are +ve only when infectious

If testing Asymptomatics randomly (vs. repeatedly) - they are MOST likely to be found post-infectious -> EXPECT Ag to be -ve MOST of time someone is PCR +ve
The very paper @CDCgov links to that concludes rapid Ag tests do not perform well in Asymptomatics literally shows 100% sensitivity for culture +ve samples in Asymptomatics

Massive failure to not emphasize this for asymptomatic screening.…
Read 6 tweets
31 Dec 20
Dec 31 2020

Out-of-control spread of SARS-CoV2

Nearly 4000 #COVID19 deaths per day in US

Vacc are many months away for most ppl

Rapid paper strip tests *could* be in everyone’s home today to curb spread immediately

Write to your congress ppl and demand they be a priority

We make it easy for you to do this and have collected signatures from leading scientists requesting congress act on these - Set aside funds that amount to <1% of the most recent stimulus bill to get these tests to everyone, quickly and for months.
FDA / others think the populous is not capable of having simple tests at home & making responsible decisions

This is insane - plus we have expensive over the counter tests that require much technology - so I guess FDA feels the wealthy can use their own data but poor cannot. BS!
Read 5 tweets
31 Dec 20
Great article bc it feels a bit haphazard (by intention) and thus captures the confusion of the current status of vaccine rollouts across the world.

But I want to talk about a specific quote in the article...

Many scientists have been frustrated that UK extended time between vaccine doses to ~12 weeks - in effort to get as many people as possible at least a single dose.

This makes sense for optimizing public health. But for optimizing individual protection it is controversial.

One scientist in the article said:

“I wouldn't want to be sitting around for 12 weeks waiting for the second dose with the partially protective vaccine,”

Under normal optimal circumstances, this opinion might be the right opinion, but In midst of a pandemic, it is faulty..

Read 13 tweets
30 Dec 20
UK has authorized AZ/Oxford vaccine.

Importantly: UK is leading the way in taking a bold public health approach (vs individual health) to getting the population vaccinated - Prioritizing distribution of 1 dose & delaying dose 2 up to 12 weeks.

This bold move is going to cause ppl to scrutinize the decision. But in this pandemic, too few governments have acted swiftly to limit spread - bc quick action sometimes means imperfect data.

Here, robust data isn’t likely available for a 12 week delay for dose 2


This was a good decision that

a) need not be permanent and suggests the UKG is willing to think with agility here and

b) likely will be the better overall public health approach rather than letting doses sit in freezers while others die and

Read 10 tweets

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