Infected versus Infectious

As I said in my post Frequent, Fast, and Cheap is Better than Sensitive we shouldn’t be comparing virus tests head-to-head, as if all tests serve the same purpose. Instead, we should recognize that tests have comparative advantages and a cheap, fast, frequent testing regime can be better in some respects than a slow, infrequent but more sensitive testing regime. Both regimes can be useful when used appropriately and especially when they are used in combination.

Eric Topol has a good graphic.

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As Topol also notes:

In order to get this done, we need a reboot at @US_FDA, which currently requires rapid tests to perform like PCR tests. That’s wrong. This is a new diagnostic category for the *infectious* endpoint, requiring new standards and prospective validation.

The FDA has sort-of indicated that they might be open to this.

Much, much too slow, of course. Matching a virus that grows exponentially against a risk-averse, overly-cautious FDA has been a recipe for disaster.

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Thanks again. Dr Michael Mina will be doing a presentation on the topic at the best source of online Covid info, the Medcram Covid update. Live on Wednesday 3pm Eastern

Seriously. Why are these not being bought and sold by the millions (billions?) as we speak. I'd by myself 100x right now if I could (can I?)

We'll see what actually shakes out of this. I wouldn't expect FDA approval of a mass market test strip until well into Q1 2021. Probably won't be available in stores until after a vaccine is out.

Keep in mind this is a country where people are hanging up on contact tracers, and apparently the illegal immigrant community is basically not cooperating at all (can you blame them?)

That's exactly why we need tools like this so that individuals can protect their circles of associates without waiting for some grand national scheme of contact tracing and universal compliance to kick in. I could have used a cheap, DIY at-home test today. I had dinner with my sister, her family, and my parents (outdoors, distanced, wearing masks when not eating). If available, I would have taken an at-home test first and stayed home, obviously, if tested positive. I'm sure I'm not the only one in this type of situation.

These tests do not need to have extremely low false-negative rates to help a lot. The alternative to these tests is not that asymptomatic individuals will act as though they are infectious, especially because with very high probability they aren't. Rather, they will go out in an absence of a positive test, including not having taken a test. So, even a test with a false-negative rate of 10% will let 90% of asymptomatic, infectious individuals know not to go out when they would have in the absence of a test.

Oh I understand the math and the rationale. We're in full agreement. But this is the United States. This is a low trust society.

My prediction is that the FDA will not allow them in any mass market situation until well after a vaccine is on the market.

Explain to me the incentive structure that would lead the FDA to allow this within a timespan in which it would actually be effective, and I'll listen. I have serious doubts. What's in it for them?

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Madarchod Kutti Ka Pilla - Tere Amriki Hindu Bibi ke Gaand Mein

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Agree with Alex that the FDA drags feet, but, in fairness, even if Americans test positive it's unlikely they will curtail their activities. I recall reading that even active TB patients cannot be held quarantined, despite laws to that effect, in the USA.

Bonus trivia: https://en.wikipedia.org/wiki/Frances_Oldham_Kelsey - "Kelsey died in London, Ontario, on August 7, 2015, at the age of 101,[24] less than 24 hours after Ontario's Lieutenant-Governor, Elizabeth Dowdeswell, visited her home to present her with the insignia of Member of the Order of Canada for her role against thalidomide" - I swear I thought her parents were famous for something or another, but I can't find the cite.

Ripped from today's headlines...if law abiding Germany is resisting, what about lawless America, 'land of the free' (community disease)? We're doomed.

BERLIN (Reuters) - Thousands marched in Berlin on Saturday [8/1/20] to protest against measures imposed in Germany to stem the coronavirus pandemic, saying they violated people’s rights and freedoms... The gathering, estimated by police at 17,000, included libertarians, constitutional loyalists and anti-vaccination activists... Others marched with placards saying ‘We are making a noise because you are stealing our freedom!’ and ‘Do think! Don’t wear a mask!’.

Bonus trivia: children can spread C-19, contrary to some earlier reports.

Measures are being imposed on healthy people whom we have no reason to suspect are infected. Forget proof beyond a reasonable doubt, even a preponderance of the evidence standard (>50% chance of infection) is not even close to being met. There are a lot of people that don't want the government imposing "measures" on healthy, innocent people but would still find a DIY at-home test useful for preventing spread amongst their circle of friends, family, co-workers, and other associates.

@BC - an infected person can lie about their status, or refuse to take any test and be an asymptomatic carrier. We're doomed.

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It doesn't matter if people want to resist self quarantining. Just like no kid can go to school without proof of vaccines, businesses, schools, restaurants and nursing homes can REQUIRE you to take this test before you are allowed to enter. Don't take a test, I don't care. You just won't be allowed to enter anywhere that prudent people are willing to go.

That would be a perfectly good solution. But it does not stroke the egos of the little men who run the bureaucracy. A free market solution does not give them power and influence.

So whatever happens we will be forced to respect the CDC's Autoriteh!

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The story that will be told decades from now about this crisis, like all crises, will be that better regulations would’ve prevented and abated it. That story will serve to teach the next generation that ever more regulation is needed.

The reality of the FDA’s failure will not be understood or appreciated. It pains me to imagine the loss of life they’re responsible for.

+1

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The FDA is blocking your $1 paper saliva test strip from being used in the US to test for infection?

Or is it the FDA has not developed the test, built the factory to make $1 test strips and turned the patents and factories over to you so you can sell the $1 cost test strips to the Federal government for $10 each?

Given no one has delivered a single prototype batch of 100,000 test strips that can be produced in billion quantity for $1 billion per day, no one knows how long it will take to get an FDA waiver. My guess is no later than January 20, 2021 after Biden is sworn in because Biden will listen to Gates, former Obama officials, and other scientists.

The FDA granted a waiver for chloroquine based on zero evidence, or totally bogus "evidence". Just listened to TWIV 647 where they discussed how you need to use lung culture cells in a lab test to see if anything affects SARS-Cov2 viruses at length. it seems lots of arm chair researchers are proving speculation with totally useless but easy lab experiments.

Yet, the FDA granted a waiver, and withdrew only after several double blind tests proved chloroquine was totally useless against COVID-19, if not dangerous.

On the other hand, the FDA has approved remdesivir, but Gilead can't meet demand.

"the FDA granted a waiver, and withdrew only after several double blind tests proved chloroquine was totally useless against COVID-19, if not dangerous."

And then those studies were withdrawn, and the weight of the evidence now shows that it is in fact effective...

The correct answer all along should have been "do what your doctor tells you, not what politicians prescribe."

The follow on, whether politicians were lucky, with advise they had no business giving, is just doubly sad. Especially given:

https://www.10tv.com/article/news/health/coronavirus/ohio-board-of-pharmacy-hydroxychloroquine-and-chloroquine-covid-19/530-ea1e8eed-0504-4e04-bcb7-fcf796a52540

https://scitechdaily.com/malaria-drug-chloroquine-does-not-inhibit-covid-19-infection-in-human-lung-cells/

https://www.sciencemag.org/news/2020/06/it-s-nightmare-how-brazilian-scientists-became-ensnared-chloroquine-politics

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The best rigorous clinical trials being run to determine the effectiveness of various covid treatment is the UK's RECOVERY Trial.

" The trial has proceeded at unprecedented speed, enrolling over 11,000 patients from 175 NHS hospitals in the UK. Throughout this time, the independent Data Monitoring Committee has reviewed the emerging data about every two weeks to determine if there is evidence that would be strong enough to affect national and global treatment of COVID-19.

‘On Thursday 4 June, in response to a request from the UK Medicines and Healthcare Products Regulatory Agency (MHRA), the independent Data Monitoring Committee conducted a further review of the data. Last night, the Committee recommended the chief investigators review the unblinded data on the hydroxychloroquine arm of the trial.

‘We have concluded that there is no beneficial effect of hydroxychloroquine in patients hospitalised with COVID-19. We have therefore decided to stop enrolling participants to the hydroxychloroquine arm of the RECOVERY Trial with immediate effect. We are now releasing the preliminary results as they have important implications for patient care and public health.

‘A total of 1542 patients were randomised to hydroxychloroquine and compared with 3132 patients randomised to usual care alone. There was no significant difference in the primary endpoint of 28-day mortality (25.7% hydroxychloroquine vs. 23.5% usual care; hazard ratio 1.11 [95% confidence interval 0.98-1.26]; p=0.10). There was also no evidence of beneficial effects on hospital stay duration or other outcomes.

‘These data convincingly rule out any meaningful mortality benefit of hydroxychloroquine in patients hospitalised with COVID-19. Full results will be made available as soon as possible.

Peter Horby, Professor of Emerging Infectious Diseases and Global Health in the Nuffield Department of Medicine, University of Oxford, and Chief Investigator for the trial, said:

‘Hydroxychloroquine and chloroquine have received a lot of attention and have been used very widely to treat COVID patients despite the absence of any good evidence. The RECOVERY Trial has shown that hydroxychloroquine is not an effective treatment in patients hospitalised with COVID-19.’

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Comes on tv with grey pubic hair coming out of his nostrils!

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Larry Winters

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This is what happened to testing: https://www.vanityfair.com/news/2020/07/how-jared-kushners-secret-testing-plan-went-poof-into-thin-air

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In Africa, we wait for you white slaves!

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As I mentioned at an earlier post, I've been advising clients/employers when an employee is diagnosed with covid. All employers fear it, because it could result in a shut-down. Waiting for test results seems like an eternity when the survival of a business is at stake. Getting test results that aren't reliable are no test results, not when the lives of the other employees are at stake. Dealing in the abstract is nice, but dealing in reality is hard. If employees don't trust the testing results, they won't come back. If the employer doesn't trust the test results, the employer will shut down because of the potential liability. I appreciate the great work Tabarrok is doing, but out here in the real world of rising cases and deaths, theory means nothing. [An aside, CDC recommends sending all employees who were in "close contact" with the employee diagnosed with covid home (so-called critical businesses are subject to a more relaxed standard). Close contact is defined as within six feet for fifteen minutes or more. Think about that: challenging employees about distance and time. With a tape measure and stop watch? While waiting for test results that may or may not be reliable. That's a morale booster.]

You advise literally no one. Go hang, good sir.

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>a recipe for disaster.

Oh, I wouldn't call it that, Ty.

It's a recipe for universal mail-in vote fraud, which has been the goal all along. And so far, so good!

It's a Recipe For Democracy, Tyler!!!!

Take a bow, my friend.

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I'm skeptical of how this will work in practice. We know that people are only infectious for about the first 6 days that they have the virus. Yet they appear to shed viral RNA for a long time after that. If this kind of testing is used to determine whether people can work, it will have the effect of needlessly keeping a lot of recovered people out of work for a long time.
That can be a good tradeoff when the virus is in the epidemic stage, but as the virus saturates and cases become rarer I don't think this can be justified. By the time this plan is approved it won't be needed.

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"Real Americans love liberty and the right to infect other people more than they love life itself."
--Benjamin Crumb

Indeed. Just before all this blew up, California repealed the law that made it a crime to knowingly infect someone with HIV.

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It probably depends on how good the test is. It would be nice to have a moderately reliable test that produces results in, at most, a few hours, but the Trump administration put the kibosh on that. Nations where the leaders actually considered COVID to be a problem were able to ramp up testing to useful levels quickly.

What do epidemiologists say about the proposed test? Would it actually help or just muddy the waters? How sensitive is it to proper administration? Everyone(*) does at least two rounds with any home pregnancy test before buying baby clothes.

(*) Actually not everyone. It's mainly women.

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White supremacy in action. It's all a conspiracy against Colored (or, "of color") people who are disproportionately victimized by the Chinese Bat Virus while White fat-cats like Jeff Bezos bask in their White Immunity.
Is that what you meant to say, Comrade "Kaleberger"?

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Founder and Chief Technology Officer Irene Bosch says her firm has field-tested it in hospitals. “What we learned is that the test is able to be very efficient for people who have a lot of virus,” she says.

That raises an obvious question. How much do we know about viral loads and infectiousness? This test was proposed back in March. Has anything been published yet? My search found zilch.

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Alex’s analysis seems to be based on the idea that multiple tests are independent. Is this true? It seems unlikely to me. For example, someone administering the test incorrectly might do so twice in a row. Or a several false positives might occur if the person being tested has related antibodies from another illness.

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Does anyone have a theory of FDA behavior? What's the downside of allowing low sensitivity screening tests?

It is going to be pretty opaque to us. It's sensitivity, and specificity, and field stability, and cost, and ability to scale.

Presumably anything that was offered with all those would be accepted. A no brainier. The harder question is what the FDA should do when only some boxes are checked.

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Not sure if it has been mentioned before, but a good discussion of the practicality of a cheap and fast COVD-19 test was given by Micheal Mina on the This Week in Virology podcast #640 https://www.microbe.tv/twiv/twiv-640/

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Question for Prof T: are support for small government, scepticism about government etc. positively or negatively correlated with efficacy of gov institutions?

My guess is, within western democracies at least, there's a negative correlation.

If so, does bad government cause the scepticism of gov, or scepticism of gov drive the bad government?

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Alex is focused on the FDA here in the US, but has any country anywhere in the entire world approved the use of tests like these? I don’t know of any, and that seems surprising. At least with the lockdown strategy, we had Sweden for comparison, but with cheap saliva tests, we have nobody. That might give us additional data on whether having access to tests like these would be useful.

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