SalivaDirect potential game changer (for the good)

[MplsGopher]

Dr. Osterholm was on WCCO this morning with Dave Lee.

he did not sound as excited about the saliva test. He said that some labs would not be able to process the test (didn't catch exactly why). He also questioned what the cost of the test would be by the time it's able to be offered to the public.

Yeah. We’re starting to get to the point where, by the time some of these tests are actually, formally proven out, production ramped up, and product rolled out ... we could be getting into vaccine time anyway.

 

[Pompous Elitist]

It’s all becoming clear, now.

Dr. Osterholm was on WCCO this morning with Dave Lee.

he did not sound as excited about the saliva test. He said that some labs would not be able to process the test (didn't catch exactly why). He also questioned what the cost of the test would be by the time it's able to be offered to the public.

When the pandemic is long over Osterholm will still be talking about catastrophic models. He is who he is.

He’d been down on any sort of rapid testing for some time now.

 

[Pompous Elitist]

Yeah. We’re starting to get to the point where, by the time some of these tests are actually, formally proven out, production ramped up, and product rolled out ... we could be getting into vaccine time anyway.

They are ready to go. They need authorization and investment money in that order.

 

[MplsGopher]

They are ready to go. They need authorization and investment money in that order.

Not proven, to an acceptable standard.

And don’t bother, not going to click on whatever YouTube click-baiter you link to.

 

[Pompous Elitist]

^^^


It’s all becoming clear, now. This from the guy that thinks a vaccine will be vetted and screened for safety and widely distributed by the end of the year. It’s going to be a lot longer than that.

Part of the resistance to at home, rapid testing is the mandate that every test result be reported to government officials. That makes things expensive and requires more personnel, increase time delay, requires software development etc. This is also what lead to the disastrous rollout of clinical EHRs, meaningful use etc etc.

Also, fear over perceived and actual liability, inertia, and potential conflicts of interest at the FDA. We are going about this all wrong.

 

[MplsGopher]

^^^


It’s all becoming clear, now. This from the guy that thinks a vaccine will be vetted and screened for safety and widely distributed by the end of the year. It’s going to be a lot longer than that.

Part of the resistance to at home, rapid testing is the mandate that every test result be reported to government officials. That makes things expensive and requires more personnel, increase time delay, requires software development etc. This is also what lead to the disastrous rollout of clinical EHRs, meaningful use etc etc.

Also, fear over perceived and actual liability, inertia, and potential conflicts of interest at the FDA. We are going about this all wrong.

Getting rid of regulations is how we got the 737 Max.

You advocate for it, only because you represent people who stand to profit from that.

 

[STPGopher]

The FDA has been the limiting factor all along. This stuff isn’t rocket science. They have test sensitivity criteria that have been difficult to meet with the rapid, paper based antigen tests.

The good news is opinion is “evolving” as the math gets explained and absorbed, and it starts to make more sense to invest billions (or a trillion) in prevention rather than cleaning up fiscal messes.

Bureaucracy moves slowly in the best of times.

The FDA has had processes in the works for decades that have been deemed effective. They are not geared for rapid prototyping/ testing. They are better at approval of new drugs and medical devices. As frustrating as they can be, they have done a relatively good job of protecting the public for a very long time!

Perhaps if we had not disbanded the Pandemic Response team?

 

[MplsGopher]

New England Journal of Medicine article, posted in another thread: https://www.nejm.org/doi/full/10.1056/NEJMp2015897

We draw several conclusions. First, diagnostic testing will help in safely opening the country, but only if the tests are highly sensitive and validated under realistic conditions against a clinically meaningful reference standard. Second, the FDA should ensure that manufacturers provide details of tests’ clinical sensitivity and specificity at the time of market authorization; tests without such information will have less relevance to patient care.

Third, measuring test sensitivity in asymptomatic people is an urgent priority. It will also be important to develop methods (e.g., prediction rules) for estimating the pretest probability of infection (for asymptomatic and symptomatic people) to allow calculation of post-test probabilities after positive or negative results. Fourth, negative results even on a highly sensitive test cannot rule out infection if the pretest probability is high, so clinicians should not trust unexpected negative results (i.e., assume a negative result is a “false negative” in a person with typical symptoms and known exposure). It’s possible that performing several simultaneous or repeated tests could overcome an individual test’s limited sensitivity; however, such strategies need validation.

 

[Cedar Rapids Gopher]

Not going to waste my time digging into a couple fringe opinions. I’ll just go with the proven scientists at the FDA and other agencies.

Yes like Dr. Facci. He honestly should have been fired. He provided so much bad information at the beginning. Then totally changed his toon. There are several examples but the one I will use here is masks.

 

[GoldenRodents]

Oh piffle, are we practicing for a really dangerous pandemic like polio, smallpox, bubonic plague?

 

[Pompous Elitist]

New England Journal of Medicine article, posted in another thread: https://www.nejm.org/doi/full/10.1056/NEJMp2015897

We draw several conclusions. First, diagnostic testing will help in safely opening the country, but only if the tests are highly sensitive and validated under realistic conditions against a clinically meaningful reference standard. Second, the FDA should ensure that manufacturers provide details of tests’ clinical sensitivity and specificity at the time of market authorization; tests without such information will have less relevance to patient care.

Third, measuring test sensitivity in asymptomatic people is an urgent priority. It will also be important to develop methods (e.g., prediction rules) for estimating the pretest probability of infection (for asymptomatic and symptomatic people) to allow calculation of post-test probabilities after positive or negative results. Fourth, negative results even on a highly sensitive test cannot rule out infection if the pretest probability is high, so clinicians should not trust unexpected negative results (i.e., assume a negative result is a “false negative” in a person with typical symptoms and known exposure). It’s possible that performing several simultaneous or repeated tests could overcome an individual test’s limited sensitivity; however, such strategies need validation.

Diagnostic testing, ie PCR is still necessary to confirm positive results.

The problem is that testing is hopelessly slow outside of small internal hospital facilities, for example.

The purpose of the rapid antigen testing is to rapidly squash large outbreaks. It doesn’t matter they are lower sensitivity. They can be repeated, cheaply and rapidly. The reporting requirements destroy that. The high sensibility requirements destroy that. Get it?

Watch the videos. Try to keep an open mind.

 

[Pompous Elitist]

The FDA has had processes in the works for decades that have been deemed effective. They are not geared for rapid prototyping/ testing. They are better at approval of new drugs and medical devices. As frustrating as they can be, they have done a relatively good job of protecting the public for a very long time!

Perhaps if we had not disbanded the Pandemic Response team?

They can approve changes to their paradigm and subvert criteria when a crisis exists for eg, cancer treatments or say, a pandemic.

Regarding the PRT there is nothing keeping the FDA from reclassifying rapid testing, other than the FDA. It would probably help to have mor political pressure but there is some level of competing interest here. A quick resolution helps Trump which may not be in the interest of some players.

 

[MplsGopher]

Diagnostic testing, ie PCR is still necessary to confirm positive results.

The problem is that testing is hopelessly slow outside of small internal hospital facilities, for example.

The purpose of the rapid antigen testing is to rapidly squash large outbreaks. It doesn’t matter they are lower sensitivity. They can be repeated, cheaply and rapidly. The reporting requirements destroy that. The high sensibility requirements destroy that. Get it?

Watch the videos. Try to keep an open mind.

Agree that diagnostic tests results that are "too" slow, ruin the helpfulness of the test. Not sure I agree that getting test results back in 2 days is too slow. 7 days or absurdly longer times obviously are.

"It doesn't matter [that] they are lower sensitivity." Depends what "lower" means.
"The reporting requirements destroy that." Sounds like nonsense. I'm unlikely to have much sympathy for this libertarian sounding viewpoint. If experts get behind it, because the testing is proven good, then I can get onboard. Not before.

 

[Pompous Elitist]

Typical garbage.

 

[MplsGopher]

Sounds like something that would be said by someone who cares more about their clients' profits, than about public health.

 

[STPGopher]

They can approve changes to their paradigm and subvert criteria when a crisis exists for eg, cancer treatments or say, a pandemic.

Regarding the PRT there is nothing keeping the FDA from reclassifying rapid testing, other than the FDA. It would probably help to have mor political pressure but there is some level of competing interest here. A quick resolution helps Trump which may not be in the interest of some players.

We are dealing with humans, so maybe some are less than thrilled to jump through hoops for Trump, but I highly doubt the majority would deliberately slow things down to make Trump look bad.

I am not sure why everything good is supposed to be because of Trump, yet any result even close to being negative is because of someone else. It seems to me that a Pandemic Response Team would have been handy to deal with the Corona virus/ covid-19. They could have helped facilitate resources to assist in rapid approval of tests and possible treatments (vaccines, etc.). They also could have reported directly to the President, etc. Instead, it appears that much time was wasted allocating resources (PPEs, test kits, etc.) in addition to time wasted trying to assemble teams to work on possible vaccine(s), or even how to guide the public.

 

[upnorthkid]

Diagnostic testing, ie PCR is still necessary to confirm positive results.

The problem is that testing is hopelessly slow outside of small internal hospital facilities, for example.

The purpose of the rapid antigen testing is to rapidly squash large outbreaks. It doesn’t matter they are lower sensitivity. They can be repeated, cheaply and rapidly. The reporting requirements destroy that. The high sensibility requirements destroy that. Get it?

Watch the videos. Try to keep an open mind.

It does to an extent. You can't just blanket say well then I'll repeat the test. If the sensitivity is only 70%, you could end up with 2 false negatives in 1/10 people who then will go out and spread a highly contagious virus none the wiser (and given we had 300+ positives here again, you can do the math on how that works), which completely negates the point of what you're trying to do. There needs to be a minimum threshold which is why even here with the current tests we are double ruling out people who get admitted if they're high suspicion because the test sensitivity isn't great. This costs time, ppe, beds, and staff to do all of which add up. In a world where there is no money and there is unlimited reagent and lab capacity, sure test til the cows come home and have no idea what to do with your results.

On the point of wanting mandated reporting, it is obviously important to know the case rate and infection penetrance so you can make educated decisions. Like on things like reopening business, schools, sports, etc. I agree that in home testing would be great and would really pull a large burden off the system, but if it's not going to be reported nor able to be enforced nor able to be acted on, it ends up causing even more confusion.

I understand what you're saying and yes the organization should do everything it can to be nimble in this endeavor (and if they are acting in ways that only seek to make the president look bad, they're pathetic human beings, which hey I guess could be the csae), but it also needs to come with the understanding that you can't just churn out bad science and hope it sticks. It's why we've had an array of fucking chaos to this point because people have fucked the data from day one.

 

[Pompous Elitist]

We are dealing with humans, so maybe some are less than thrilled to jump through hoops for Trump, but I highly doubt the majority would deliberately slow things down to make Trump look bad.

I am not sure why everything good is supposed to be because of Trump, yet any result even close to being negative is because of someone else. It seems to me that a Pandemic Response Team would have been handy to deal with the Corona virus/ covid-19. They could have helped facilitate resources to assist in rapid approval of tests and possible treatments (vaccines, etc.). They also could have reported directly to the President, etc. Instead, it appears that much time was wasted allocating resources (PPEs, test kits, etc.) in addition to time wasted trying to assemble teams to work on possible vaccine(s), or even how to guide the public.

I‘m the last person on earth that will defend Trump’s leadership during this crisis. The PPE fiasco goes far beyond his incompetence.

We’re looking for solutions, not stupid political arguments.

 

[Pompous Elitist]

It does to an extent. You can't just blanket say well then I'll repeat the test. If the sensitivity is only 70%, you could end up with 2 false negatives in 1/10 people who then will go out and spread a highly contagious virus none the wiser (and given we had 300+ positives here again, you can do the math on how that works), which completely negates the point of what you're trying to do. There needs to be a minimum threshold which is why even here with the current tests we are double ruling out people who get admitted if they're high suspicion because the test sensitivity isn't great. This costs time, ppe, beds, and staff to do all of which add up. In a world where there is no money and there is unlimited reagent and lab capacity, sure test til the cows come home and have no idea what to do with your results.

On the point of wanting mandated reporting, it is obviously important to know the case rate and infection penetrance so you can make educated decisions. Like on things like reopening business, schools, sports, etc. I agree that in home testing would be great and would really pull a large burden off the system, but if it's not going to be reported nor able to be enforced nor able to be acted on, it ends up causing even more confusion.

I understand what you're saying and yes the organization should do everything it can to be nimble in this endeavor (and if they are acting in ways that only seek to make the president look bad, they're pathetic human beings, which hey I guess could be the csae), but it also needs to come with the understanding that you can't just churn out bad science and hope it sticks. It's why we've had an array of fucking chaos to this point because people have fucked the data from day one.

The current test regimen already completely negates what we‘re trying to do. Getting results 3-14 days after symptom or being informed of a high risk exposure days to weeks later (likely even further down the infection timeline) is totally worthless. The current system is not working in the hotspots that need test results the quickest.

You answered your own question there. Positive tests means don‘t go to school, work that day. Get a PCR as is routine today. Of course confirmatory PCR testing still has a role in clinical management and public health surveillance. We’re already undercounting cases by a minimum of 10x. The data is messy as hell. You know this. I fail to see why a statistical estimate cannot be achieved by ongoing community PCR surveillance, in addition to at home testing.

Agree on that.

Think of the rapid testing as an early warning flag, prior to symptoms. Reduce presymptomatic spread which is really the key feature that makes this virus transmit so easily.

 

[STPGopher]

I‘m the last person on earth that will defend Trump’s leadership during this crisis. The PPE fiasco goes far beyond his incompetence.

We’re looking for solutions, not stupid political arguments.

Ummm, okay. BTW PPE's are still a part of the solution.

On to testing. Results can be as soon as same day or next day even on the (Nose) swab test. Part of that tells me that resources/ resource allocation could help shrink test times for the general public. SIAP but I am beginning to think that labs at some college campuses (that aren't already being used) might be able to be used to expand test processing.

 

[Pompous Elitist]

Ummm, okay. BTW PPE's are still a part of the solution.

On to testing. Results can be as soon as same day or next day even on the (Nose) swab test. Part of that tells me that resources/ resource allocation could help shrink test times for the general public. SIAP but I am beginning to think that labs at some college campuses (that aren't already being used) might be able to be used to expand test processing.

I’ve been ripping on PPE supply from day 1. You’re late to the party. Too late for many.

Sometimes, yes. There are local labs, POC tests but they are few and still relatively expensive. They are far from the norm. There are supply chain bottlenecks not easily solved - reagents, etc. Technology fragmentation (shades of government meddling in EHR tech and mandates). Experts I’ve read have stated there are limits to the amount of PCRs that can be realistically performed on a daily basis. Obviously scarcity opens up bidding wars and other capitalistic hijinks. Universities are positioned to have some access to testing, in-house expertisebut their supply chains are unknown.

Open your mind to new possibilities. The current paradigm has failed, badly.

 

[STPGopher]

It does to an extent. You can't just blanket say well then I'll repeat the test. If the sensitivity is only 70%, you could end up with 2 false negatives in 1/10 people who then will go out and spread a highly contagious virus none the wiser (and given we had 300+ positives here again, you can do the math on how that works), which completely negates the point of what you're trying to do. There needs to be a minimum threshold which is why even here with the current tests we are double ruling out people who get admitted if they're high suspicion because the test sensitivity isn't great. This costs time, ppe, beds, and staff to do all of which add up. In a world where there is no money and there is unlimited reagent and lab capacity, sure test til the cows come home and have no idea what to do with your results.

On the point of wanting mandated reporting, it is obviously important to know the case rate and infection penetrance so you can make educated decisions. Like on things like reopening business, schools, sports, etc. I agree that in home testing would be great and would really pull a large burden off the system, but if it's not going to be reported nor able to be enforced nor able to be acted on, it ends up causing even more confusion.

I understand what you're saying and yes the organization should do everything it can to be nimble in this endeavor (and if they are acting in ways that only seek to make the president look bad, they're pathetic human beings, which hey I guess could be the csae), but it also needs to come with the understanding that you can't just churn out bad science and hope it sticks. It's why we've had an array of fucking chaos to this point because people have fucked the data from day one.

I’ve been ripping on PPE supply from day 1. You’re late to the party. Too late for many.

Sometimes, yes. There are local labs, POC tests but they are few and still relatively expensive. They are far from the norm. There are supply chain bottlenecks not easily solved - reagents, etc. Technology fragmentation (shades of government meddling in EHR tech and mandates). Experts I’ve read have stated there are limits to the amount of PCRs that can be realistically performed on a daily basis. Obviously scarcity opens up bidding wars and other capitalistic hijinks. Universities are positioned to have some access to testing, in-house expertisebut their supply chains are unknown.

Open your mind to new possibilities. The current paradigm has failed, badly.

Ummm That kind of is opening up. There is no one fix. Not on something of this magnitude. There should be war time like efforts. If Universities can be part of the solution even if it is only like a 10% increase, then do it.

Since politics are creeping back in, there are most likely still some things that can be done collaboratively. Assisting the private sector to increase production of test kits/ reagents come to mind.

Assisting with supply chain issues is an area where the government can help. Many quality standards used today were created by the Military.

 

[Pompous Elitist]

I don’t disagree with any of that.

I’m not sure where the negative reaction to new testing ideas is coming from, however. Can you go into greater detail of your position on this?

 

[MplsGopher]

The only negative part is that they haven't been proven to be sufficiently sensitive, yet. You've already been disproven that any level of sensitivity is still good. If they aren't, that's just a snake oil cash grab.

Same thing as the flood of crappy antibody tests that came in when regulations were bypassed in the name of speed.


If they're proven to be reliably accurate, good tests, then they absolutely should be utilized, so long as the results continue to be required to report to the government for tracking and decision making.


Then you just have to get over the last problem: how do you convince people who don't feel sick, to get tested???

 

[Pompous Elitist]

Then you just have to get over the last problem: how do you convince people who don't feel sick, to get tested???

Convenience, concern to avoid infecting loved ones, workplace requirements.

The irresponsible crowd, ie 18-35 is well on their way to group-specific herd immunity.

 

[upnorthkid]

Convenience, concern to avoid infecting loved ones, workplace requirements.

The irresponsible crowd, ie 18-35 is well on their way to group-specific herd immunity.

that hasn't been the case and you well know it. you won't convince people who don't want to wear masks to go ahead and be tested with regular frequency to ensure they are caught in that phase. it's already been a discussion about rights and now you mandate that you must take this sample x times a week. it'snot going to fly

 

[upnorthkid]

The current test regimen already completely negates what we‘re trying to do. Getting results 3-14 days after symptom or being informed of a high risk exposure days to weeks later (likely even further down the infection timeline) is totally worthless. The current system is not working in the hotspots that need test results the quickest.

You answered your own question there. Positive tests means don‘t go to school, work that day. Get a PCR as is routine today. Of course confirmatory PCR testing still has a role in clinical management and public health surveillance. We’re already undercounting cases by a minimum of 10x. The data is messy as hell. You know this. I fail to see why a statistical estimate cannot be achieved by ongoing community PCR surveillance, in addition to at home testing.

Agree on that.

Think of the rapid testing as an early warning flag, prior to symptoms. Reduce presymptomatic spread which is really the key feature that makes this virus transmit so easily.

bold 1: if you have symptoms of COVID, you should be quarantining. Having a negative rapid test does not clear you from this, particularly if you have a test as low of sensitivity as would be available. You're then saying just get a confirmatory PCR. That then leaves you in the exact same position you are already in. The point of a screening test is high sensitivity. you want to catch everyone with disease. if you cross react and get some false positives, you'd rather have that and then rule out with the confirmatory gold standard, not the other way around.

bold 2: i agree with that point completely and that is a fault of public health officials if there is that great a deal of delay. having a rapid test does not eliminate this possibility. It may reduce it somewhat, but it does not eliminate it which is gets at the problem regardless.

bold 3: well of course. The same would apply to a high risk exposure or symptomatic person awaiting their test.

bold 4: i agree with that and that is the fault of the world for not reacting to this appropriately, the government for reducing funding in ways it should not have, for simply not being ready. it is a sad state of affairs that we reacted as poorly as we did when we had substantial lead time.

bold 5: let me know how getting people to sign up for community PCR testing goes. Additionally using at home testing is great, again with the caveat you have a reliable test. Further both of these require having lab space, reagent, machines, etc. to be running frequent tests. We don't right now and we won't if you're advocating for the frequency of testing this will require (ie you'd need multiple tests a week to reduce the possible infectious time to as minimal as possible).

I agree a rapid test would be awesome. I really hope we get one soon. I work in healthcare and it would make the life of our patients (and my own) substantially easier if we had one that was effective. I think, in all honest, you and I could have a discussion on its merits and it would be fruitful if we knew the actual numbers. We're both hypothesizing and fall on alternate sides of the coin on it. I am fearful of false negatives leading to people thinking they're not infectious and spreading the disease further. You like the idea of having larger screening even if its at lower sensitivity. The issue is we don't know what that number is for this test and which group will be much higher. If it's a good test, then I'm all for it; but I'd rather see the numbers first before I tell my family and friends that's the way to go rather than getting a more reliable test and quarantining at home in the interval (our testing turnaround here has been substantially better than the high end you're talking, but obviously there are outliers around the country).

 

[Pompous Elitist]

bold 1: if you have symptoms of COVID, you should be quarantining. Having a negative rapid test does not clear you from this, particularly if you have a test as low of sensitivity as would be available. You're then saying just get a confirmatory PCR. That then leaves you in the exact same position you are already in. The point of a screening test is high sensitivity. you want to catch everyone with disease. if you cross react and get some false positives, you'd rather have that and then rule out with the confirmatory gold standard, not the other way around.

bold 2: i agree with that point completely and that is a fault of public health officials if there is that great a deal of delay. having a rapid test does not eliminate this possibility. It may reduce it somewhat, but it does not eliminate it which is gets at the problem regardless.

bold 3: well of course. The same would apply to a high risk exposure or symptomatic person awaiting their test.

bold 4: i agree with that and that is the fault of the world for not reacting to this appropriately, the government for reducing funding in ways it should not have, for simply not being ready. it is a sad state of affairs that we reacted as poorly as we did when we had substantial lead time.

bold 5: let me know how getting people to sign up for community PCR testing goes. Additionally using at home testing is great, again with the caveat you have a reliable test. Further both of these require having lab space, reagent, machines, etc. to be running frequent tests. We don't right now and we won't if you're advocating for the frequency of testing this will require (ie you'd need multiple tests a week to reduce the possible infectious time to as minimal as possible).

I agree a rapid test would be awesome. I really hope we get one soon. I work in healthcare and it would make the life of our patients (and my own) substantially easier if we had one that was effective. I think, in all honest, you and I could have a discussion on its merits and it would be fruitful if we knew the actual numbers. We're both hypothesizing and fall on alternate sides of the coin on it. I am fearful of false negatives leading to people thinking they're not infectious and spreading the disease further. You like the idea of having larger screening even if its at lower sensitivity. The issue is we don't know what that number is for this test and which group will be much higher. If it's a good test, then I'm all for it; but I'd rather see the numbers first before I tell my family and friends that's the way to go rather than getting a more reliable test and quarantining at home in the interval (our testing turnaround here has been substantially better than the high end you're talking, but obviously there are outliers around the country).

You have to look at what the test is actually doing. It will detect people in the infectious phase with high sensitivity. It is not as sensitive in the very early phase and tail phase whereas PCR will amplify very low levels of RNA that are less relevant. The sensitivity issue is a red herring as Dr Mina and others eloquently explain.

If you’re going to argue testing is important but also argue people aren’t going to do it, well that seems like an incongruous and illogical position, We should be pulling out all the stops to squash outbreaks and future epidemics earlier.

If you’re worried about false negatives are you not concerned about very slow turnaround? Symptomatics will stay home, already. We’re trying to catch presympomatics, primarily. PCR, unless POC machinery and materials becomes cheap and widespread cannot do that with enough speed or convenience, not to mention cost.

 

[swelna]

Convenience, concern to avoid infecting loved ones, workplace requirements.

The irresponsible crowd, ie 18-35 is well on their way to group-specific herd immunity.

Workplace requirements will go the furthest I believe. IDK about you, but a good portion of those who are resisting masks are 35+ (not all of them, but still) and I would not be surprised if a decent majority of them would also oppose regular testing...

 

[STPGopher]

I don’t disagree with any of that.

I’m not sure where the negative reaction to new testing ideas is coming from, however. Can you go into greater detail of your position on this?

Sorry, was that toward me? I am never negative toward new Ideas/ brainstorming. That is IMHO New product/ process development 101. With rapid vetting of course.