His Flatulence says the FDA can't regulate laboratory tests

[Loren Pechtel]

https://www.washingtonpost.com/health/2020/08/20/trump-fda-tests-coronavirus/?amp=1

If not the FDA, who? Are companies free to claim anything they want?

 

[Jimmy Higgins]

https://www.washingtonpost.com/health/2020/08/20/trump-fda-tests-coronavirus/?amp=1

If not the FDA, who? Are companies free to claim anything they want?

Well, that has been working for snake oils for a while.

But supporters cheered the change as long overdue, saying it could help get new and more innovative tests to market more quickly. They said that the FDA review process sharply slowed testing at the beginning of the pandemic and that the new policy could ensure such bottlenecks don’t recur.

I reminded of She-Ra... you had the bad guys, The Hoarde and they had their "Hoarde Science", whcih meant it was bad. And now, it seems science is just inconvenient for too many people. So let's just pretend it doesn't matter.

 

[Loren Pechtel]

https://www.washingtonpost.com/health/2020/08/20/trump-fda-tests-coronavirus/?amp=1

If not the FDA, who? Are companies free to claim anything they want?

Well, that has been working for snake oils for a while.

But supporters cheered the change as long overdue, saying it could help get new and more innovative tests to market more quickly. They said that the FDA review process sharply slowed testing at the beginning of the pandemic and that the new policy could ensure such bottlenecks don’t recur.

I reminded of She-Ra... you had the bad guys, The Hoarde and they had their "Hoarde Science", whcih meant it was bad. And now, it seems science is just inconvenient for too many people. So let's just pretend it doesn't matter.

There actually were some issues with the FDA slowing things needlessly. They were demanding that tests not give a false positive for Sars-Cov-1. Fine for a final test, not reasonable for an emergency use authorization at a time when there was no human spread of Sars-Cov-1.

 

[Bomb#20]

https://www.washingtonpost.com/health/2020/08/20/trump-fda-tests-coronavirus/?amp=1

If not the FDA, who? Are companies free to claim anything they want?

How about the CDC and the NIH? The FDA is optimized to handle steady-state medical needs, not epidemics. The FDA has a built-in institutional bias toward making the perfect be the enemy of the good.

https://www.theatlantic.com/health/...every-american-for-covid-19-every-day/615217/

"Working with two manufacturers, e25 thinks that it could make 4 million tests a month as soon as it receives FDA approval. Within six weeks of approval, it could make 20 million to 40 million tests a month. In short, e25 could single-handedly add as many as 1.2 million tests a day to the national total.

But FDA approval has not yet arrived, because the FDA compares every test to PCR, and no antigen test, however advanced, can stand up to the accuracy and sensitivity of the PCR technique. “The FDA, early on in the outbreak, said we had to follow a rubric of 80 percent sensitivity compared to PCR. How they got that number, I’m uncertain, but my best guess is it came from influenza epidemics in the past,” Herrera said.

This requirement has made antigen tests worse, Herrera argues, because it causes manufacturers to prioritize sensitivity at the cost of speed or convenience. It’s why other antigen tests use readers, or centrifuges, or look for nucleocapsid, he contends. By slightly weakening those guidelines, to 60 or 70 percent sensitivity, the FDA could let cheaper at-home tests come to market. ...

While antigen tests need the equivalent of 100,000 viral strands per milliliter, a typical PCR test can detect a positive from as little as 1,000 strands per milliliter. There is only about a day at the beginning of an infection when the two tests would give different results—when there are more than 1,000 viral strands per milliliter of your saliva or snot but fewer than 100,000, according to Dan Larremore, a mathematician at the University of Colorado at Boulder. During that period—approximately day two or day three of an infection—antigen tests are truly inferior to PCR tests.

Yet the opposite is true as COVID-19 fades: There are potentially weeks at the end of an infection when there is enough viral RNA to clear the threshold for a positive PCR test but not enough to set off an antigen test. During that period, antigen tests, such as e25’s, outperform PCR tests, Mina argues, because they identify only people who are still contagious. So why, he asks, are they judged against PCR tests—and kept off the market—for failing to find the virus when there is no intact virus to find?"

 

[Loren Pechtel]

https://www.washingtonpost.com/health/2020/08/20/trump-fda-tests-coronavirus/?amp=1

If not the FDA, who? Are companies free to claim anything they want?

How about the CDC and the NIH? The FDA is optimized to handle steady-state medical needs, not epidemics. The FDA has a built-in institutional bias toward making the perfect be the enemy of the good.

https://www.theatlantic.com/health/...every-american-for-covid-19-every-day/615217/

"Working with two manufacturers, e25 thinks that it could make 4 million tests a month as soon as it receives FDA approval. Within six weeks of approval, it could make 20 million to 40 million tests a month. In short, e25 could single-handedly add as many as 1.2 million tests a day to the national total.

But FDA approval has not yet arrived, because the FDA compares every test to PCR, and no antigen test, however advanced, can stand up to the accuracy and sensitivity of the PCR technique. “The FDA, early on in the outbreak, said we had to follow a rubric of 80 percent sensitivity compared to PCR. How they got that number, I’m uncertain, but my best guess is it came from influenza epidemics in the past,” Herrera said.

This requirement has made antigen tests worse, Herrera argues, because it causes manufacturers to prioritize sensitivity at the cost of speed or convenience. It’s why other antigen tests use readers, or centrifuges, or look for nucleocapsid, he contends. By slightly weakening those guidelines, to 60 or 70 percent sensitivity, the FDA could let cheaper at-home tests come to market. ...

While antigen tests need the equivalent of 100,000 viral strands per milliliter, a typical PCR test can detect a positive from as little as 1,000 strands per milliliter. There is only about a day at the beginning of an infection when the two tests would give different results—when there are more than 1,000 viral strands per milliliter of your saliva or snot but fewer than 100,000, according to Dan Larremore, a mathematician at the University of Colorado at Boulder. During that period—approximately day two or day three of an infection—antigen tests are truly inferior to PCR tests.

Yet the opposite is true as COVID-19 fades: There are potentially weeks at the end of an infection when there is enough viral RNA to clear the threshold for a positive PCR test but not enough to set off an antigen test. During that period, antigen tests, such as e25’s, outperform PCR tests, Mina argues, because they identify only people who are still contagious. So why, he asks, are they judged against PCR tests—and kept off the market—for failing to find the virus when there is no intact virus to find?"

They also miss early infections, returning false negatives.

There might be a role for follow-up testing but it doesn't sound too good for general testing.

 

[Bomb#20]

They also miss early infections, returning false negatives.

There might be a role for follow-up testing but it doesn't sound too good for general testing.

This is what I mean about making the perfect the enemy of the good. Yes, antigen tests will miss some early infections. But they will not miss nearly as many early infections due to their insensitivity as PCR tests will miss due to there not being enough PCR tests available, or any feasible way to ramp them up to anywhere near the extent needed.

 

[Jarhyn]

So, my job now is actually working at a bioassay company. I can tell you right off the bat that false positives are acceptable to some degree. It is the false negatives that absolutely are not allowed.

Edit: NOBODY where I work at disagrees with this model. Everyone understands and accepts it. It is SOP in bioassay for contagious diseases, and always has been, and we all understand why it always should be: it's easier and safer to accidentally quarantine on a false positive than it is to quarantine 30 people who now have been infected (or exposed) following the release of a false negative without quarantine.

It's better to not be tested than test false negative, because when you haven't been tested yet, the assumption is always expected to be "positive until proven otherwise". A false negative means comfort in exposing people.

Or in simpler terms conservatives might be able to understand "Better Safe Than Sorry"

 

[Bomb#20]

So, my job now is actually working at a bioassay company. I can tell you right off the bat that false positives are acceptable to some degree. It is the false negatives that absolutely are not allowed.

Edit: NOBODY where I work at disagrees with this model. Everyone understands and accepts it.

If that's really true, then it only means you all have a business reason to accept it, not a public health reason to accept it. (Or else it means that none of you are statisticians; at a bioassay company I very much hope that is not the case!) What you claim is utterly contradictory to everything we know about probability. So I did an independent sanity check on its reasonableness, as follows: a two second Google search for the phrase "pcr coronavirus test false negative". Here's what Google turned up:

https://www.nejm.org/doi/full/10.1056/NEJMp2015897

"In days 1 through 7 after onset of illness, 11% of sputum, 27% of nasal, and 40% of throat samples were deemed falsely negative."

"In a preprint systematic review of five studies ... false negatives ranged from 2 to 29%."

https://www.itnonline.com/content/c...give-false-negative-results-if-used-too-early

"A new study confirms what many suspected, that PCR testing even 8 days after infection shows 20 percent false negatives"

"Or in simpler terms conservatives might be able to understand "Better Safe Than Sorry"

I'm not a conservative. Stop presuming that what you need to do with anyone who disagrees with you is put him in whichever mental box you use to give yourself permission to ignore outside input. Or in simpler terms employees at bioassay companies might be able to understand:

if false negatives really were absolutely not allowed then we would not test people at all.

This is a special case of a more general point. Just as demanding exemption from the Second Law of Thermodynamics is a guaranteed blunder from the get-go, demanding exemption from cost/benefit analysis is a guaranteed blunder from the get-go.

 

[Jarhyn]

demanding exemption from cost/benefit analysis is a guaranteed blunder from the get-go.

LOLWUT? This is a public health question. No test for contagious disease gets through the FDA with statistically significant false negatives.

The cost/benefit doesn't mean for shit. This is a public health concern, and tests need to not miss people.

Get off your arm chair.

 

[Bomb#20]

demanding exemption from cost/benefit analysis is a guaranteed blunder from the get-go.

LOLWUT? This is a public health question. No test for contagious disease gets through the FDA with statistically significant false negatives.

The cost/benefit doesn't mean for shit. This is a public health concern, and tests need to not miss people.

Get off your arm chair.

My arm chair?!? You're the one engaging in arm-chair science -- you're arguing in effect that Johns Hopkins must be wrong because you have faith in the FDA not letting things like that happen. Get a grip. Why on earth would anyone take your word over that of Johns Hopkins? If you want our readers to believe their study was wrong, point out where Johns Hopkins screwed up.

 

[Loren Pechtel]

demanding exemption from cost/benefit analysis is a guaranteed blunder from the get-go.

LOLWUT? This is a public health question. No test for contagious disease gets through the FDA with statistically significant false negatives.

The cost/benefit doesn't mean for shit. This is a public health concern, and tests need to not miss people.

Get off your arm chair.

They would never approve a test with false negatives if better could be done. The FDA can't make detection possible, though.

 

[Jarhyn]

demanding exemption from cost/benefit analysis is a guaranteed blunder from the get-go.

LOLWUT? This is a public health question. No test for contagious disease gets through the FDA with statistically significant false negatives.

The cost/benefit doesn't mean for shit. This is a public health concern, and tests need to not miss people.

Get off your arm chair.

They would never approve a test with false negatives if better could be done. The FDA can't make detection possible, though.

Detection without significant false negatives is absolutely possible. Pretty sure I can't go deeper into it than that without violating an NDA, though.

 

[Jarhyn]

demanding exemption from cost/benefit analysis is a guaranteed blunder from the get-go.

LOLWUT? This is a public health question. No test for contagious disease gets through the FDA with statistically significant false negatives.

The cost/benefit doesn't mean for shit. This is a public health concern, and tests need to not miss people.

Get off your arm chair.

My arm chair?!? You're the one engaging in arm-chair science -- you're arguing in effect that Johns Hopkins must be wrong because you have faith in the FDA not letting things like that happen. Get a grip. Why on earth would anyone take your word over that of Johns Hopkins? If you want our readers to believe their study was wrong, point out where Johns Hopkins screwed up.

I work in bioassay, particularly Covid. My best friend works Covid bioassay. I talk with biochemists, directly, every day at work. I talk with biochemists every day AFTER work. My work is specifically on improving and identifying the specificity of COVID testing.

What is it that you do, again, exactly?

 

[Gun Nut]

My arm chair?!? You're the one engaging in arm-chair science -- you're arguing in effect that Johns Hopkins must be wrong because you have faith in the FDA not letting things like that happen. Get a grip. Why on earth would anyone take your word over that of Johns Hopkins? If you want our readers to believe their study was wrong, point out where Johns Hopkins screwed up.

I work in bioassay, particularly Covid. My best friend works Covid bioassay. I talk with biochemists, directly, every day at work. I talk with biochemists every day AFTER work. My work is specifically on improving and identifying the specificity of COVID testing.

God's speed, sir... God's speed with you go..

 

[Loren Pechtel]

They would never approve a test with false negatives if better could be done. The FDA can't make detection possible, though.

Detection without significant false negatives is absolutely possible. Pretty sure I can't go deeper into it than that without violating an NDA, though.

If you don't pull in viral particles you can't detect them in the sample.

 

[ZiprHead]

They would never approve a test with false negatives if better could be done. The FDA can't make detection possible, though.

Detection without significant false negatives is absolutely possible. Pretty sure I can't go deeper into it than that without violating an NDA, though.

If you don't pull in viral particles you can't detect them in the sample.

That's not a false negative. That's a negative sample.

 

[Jarhyn]

If you don't pull in viral particles you can't detect them in the sample.

That's not a false negative. That's a negative sample.

Exactly. But because I'm under NDA I can't give the exact number of viral copies it takes to produce a positive result on a test coming out of my lab, but that number is VERY low.

 

[Bomb#20]

Why on earth would anyone take your word over that of Johns Hopkins? If you want our readers to believe their study was wrong, point out where Johns Hopkins screwed up.

I work in bioassay, particularly Covid. My best friend works Covid bioassay. I talk with biochemists, directly, every day at work. I talk with biochemists every day AFTER work. My work is specifically on improving and identifying the specificity of COVID testing.

What is it that you do, again, exactly?

Get shot at for delivering unwelcome messages, apparently. My credentials are immaterial because I'm not suggesting anyone take my word for anything. I posted links to the testimony of medical researchers who you're contradicting. Our readers can read those links for themselves and reach their own conclusions as to whether it's you or the researchers who have made a better case.

So why are you asking me what I do, exactly? That's asking the mailman what he does, exactly, when you don't like what a letter says. Why don't you go ask "Lauren M. Kucirka, MD, PhD, Stephen A. Lauer, PhD, Oliver Laeyendecker, PhD, MBA, Denali Boon, PhD, Justin Lessler, PhD" what they do, exactly?

"Over the 4 days of infection before the typical time of symptom onset (day 5), the probability of a false-negative result in an infected person decreases from 100% (95% CI, 100% to 100%) on day 1 to 67% (CI, 27% to 94%) on day 4. On the day of symptom onset, the median false-negative rate was 38% (CI, 18% to 65%). This decreased to 20% (CI, 12% to 30%) on day 8 (3 days after symptom onset)..."

 

[Loren Pechtel]

If you don't pull in viral particles you can't detect them in the sample.

That's not a false negative. That's a negative sample.

But it shows up as a patient who has the infection but tests negative..

 

[Jarhyn]

Why on earth would anyone take your word over that of Johns Hopkins? If you want our readers to believe their study was wrong, point out where Johns Hopkins screwed up.

I work in bioassay, particularly Covid. My best friend works Covid bioassay. I talk with biochemists, directly, every day at work. I talk with biochemists every day AFTER work. My work is specifically on improving and identifying the specificity of COVID testing.

What is it that you do, again, exactly?

Get shot at for delivering unwelcome messages, apparently. My credentials are immaterial because I'm not suggesting anyone take my word for anything. I posted links to the testimony of medical researchers who you're contradicting. Our readers can read those links for themselves and reach their own conclusions as to whether it's you or the researchers who have made a better case.

So why are you asking me what I do, exactly? That's asking the mailman what he does, exactly, when you don't like what a letter says. Why don't you go ask "Lauren M. Kucirka, MD, PhD, Stephen A. Lauer, PhD, Oliver Laeyendecker, PhD, MBA, Denali Boon, PhD, Justin Lessler, PhD" what they do, exactly?

"Over the 4 days of infection before the typical time of symptom onset (day 5), the probability of a false-negative result in an infected person decreases from 100% (95% CI, 100% to 100%) on day 1 to 67% (CI, 27% to 94%) on day 4. On the day of symptom onset, the median false-negative rate was 38% (CI, 18% to 65%). This decreased to 20% (CI, 12% to 30%) on day 8 (3 days after symptom onset)..."

I am flushing their shit down the toilet because, quite frankly, it doesn't matter what the tests that they have access to for their study can detect, when. What matters is what a curacy can be achieved with tests. So a bunch of shit ass tests can't pass FDA. No skin off my nose.

It isn't a problem for my lab. Then again our testing is about an order of magnitude more sensitive than conventional Covid testing models so ¯\_(ツ)_/¯ (we're still working hard on it; FDA did set a pretty high bar, but we're pretty close).

All you can do is read things that have no bearing on whether testing methods be improved upon, and how. If you don't like the fact that the FDA doesn't want to approve shit tests, posting "the tests are shit" isn't going to change the fact that they are.

In fact, the earlier tests are much more shit. There were fewer [and less-]functional binding antibodies and antigens just a month ago, and you're using historic averages to determine how and whether false negatives are actually avoidable? That's cute. It's really fucking stupid... But cute.