Conoravirus ...

[Slick470]

The cell phone data is interesting, yet creepy. I know it's anonymous data, but still...

I've heard that is how all those gps maps tell you there is a slowdown ahead when you are driving too.

[Ajax]

The cell phone data is interesting, yet creepy. I know it's anonymous data, but still...

I've heard that is how all those gps maps tell you there is a slowdown ahead when you are driving too.

It's true. Doesn't mean I like it any better.

[Slick470]

just remember, big brother and big data are always watching... hi guys!

[Tim Ford]

For the covid19 test swab that was collected on March 17, my results are NEGATIVE.

Steve

Whew!

That's great!
My question revolves around the new "instant" test. (my wife's took 5 days)

To anyone of you with some molecular biology background, how the hell do you do PCR in 15 minutes? Or if there's no in vitro amplification of the RNA genome, how the hell do you test for a very specific sequence with that small a sample? Can you fine tune mass spec for a specific kDa spike that signals SAR CoV-2 presence?

Thanks for any info.

[BeauV]

For the covid19 test swab that was collected on March 17, my results are NEGATIVE.

Steve

Whew!

That's great!
My question revolves around the new "instant" test. (my wife's took 5 days)

To anyone of you with some molecular biology background, how the hell do you do PCR in 15 minutes? Or if there's no in vitro amplification of the RNA genome, how the hell do you test for a very specific sequence with that small a sample? Can you fine tune mass spec for a specific kDa spike that signals SAR CoV-2 presence?

Thanks for any info.

The Abbot Labs device (size of a toaster) provides a "NO" in 5 minutes and a "YES" in 15 min. I have no idea how it works, but there are versions of it being tested at UCSF and it works great. I did learn that when one gets a "panel" of results from the machine there are literally dozens of viruses present in people. One Dr. said that typically a healthy person will have between 20 and 40 viruses show up. That was news to me.

[Ajax]

We are disgusting, walking biomes. Definitely not "clean." Probably for the best, or we'd have no immunity.

[Chris Chesley]

We got some experts here on Scantlings. This morning's article by Karl Denninger. Can you refute it?


https://www.market-ticker.org/akcs-www?post=238752

[Ajax]

We got some experts here on Scantlings. This morning's article by Karl Denninger. Can you refute it?


https://www.market-ticker.org/akcs-www?post=238752

Here's a quote from the linked article:

That's a long quote but you have to read the entire thing and let it sink into your head. If you maintain the practices until the new cases dwindle you have not actually changed anything -- you have only delayed it.

That's the whole point of the isolation- to delay, and spread it out over time, so that the medical system isn't overwhelmed. Here's what's not in dispute- New York City is stacking bodies inside of rented refrigeration trucks because the morgues are full. It's not a theory, it's actually happening.

Whether or not we'd reach 2.2 million deaths is irrelevant. Medical systems are being overwhelmed NOW. That means that if you break an arm or otherwise injure yourself, you should expect to be triaged and sent to the back of the line and spend a considerable amount of time in pain because there are no immediate resources to treat you. Is that what you want?

This isn't a situation where there are 2 medical systems- one for virus patients and another for "everyone else." Our national medical effort is consumed with preventing and treating this disease. If we can delay and spread this out over time so that the hospitals can handle it, that means you'll get prompt treatment when you fall off a ladder or have a heart attack. It means a ventilator might be available for you if you have a stroke and enter a coma for a week or two. That's what I want.

[kdh]

I think Ajax is right. The article is basically true--we're just delaying getting to herd immunity, and that's not particularly likely to come from a vaccine. What the writer does leave out is a treatment effective enough to avoid hospitalizations and improve survival. That would be a game-changer and worth increasing its probability by delaying infections. Also, letting the disease run its course sounds theoretically reasonable, but as Ajax points out do we want huge numbers of people sick with some dying at home because hospitals are turning them away?

I'll confess though, that my mental model of what happens when my family get sick is for us to take Tylenol and monitor our oxygen uptake with an oximeter, do everything we can not to need help.

On the lack of consistent area-under-the-curves with two scenarios presented by our government. I think implicit in these graphs is that they don't represent the full course of the epidemic, that the first bumps represent just our initial efforts and that there will be subsequent infections and graph bumps associated with future easing and re-establishment of isolation measures.

[Slick470]

For the covid19 test swab that was collected on March 17, my results are NEGATIVE.

Steve

Whew!

That's great!
My question revolves around the new "instant" test. (my wife's took 5 days)

To anyone of you with some molecular biology background, how the hell do you do PCR in 15 minutes? Or if there's no in vitro amplification of the RNA genome, how the hell do you test for a very specific sequence with that small a sample? Can you fine tune mass spec for a specific kDa spike that signals SAR CoV-2 presence?

Thanks for any info.

The Abbot Labs device (size of a toaster) provides a "NO" in 5 minutes and a "YES" in 15 min. I have no idea how it works, but there are versions of it being tested at UCSF and it works great. I did learn that when one gets a "panel" of results from the machine there are literally dozens of viruses present in people. One Dr. said that typically a healthy person will have between 20 and 40 viruses show up. That was news to me.

A note from my wife, who is tracking this stuff for her job... the new Abbott device that, per its own product insert, "Negative results do not preclude SARS-CoV-2 infection". https://ensur.invmed.com/ensur/contentA ... 55.4175589

[Ajax]

We're being very careful at home to avoid ANY injury or illness so that we don't burden the medical system right now...or have to sit in an ER waiting for treatment with sick people.

It's easy to look at quarantine as a chance to catch up on all those home projects but you've got to be careful climbing ladders, working on home electrical systems and using power tools like saws and whatnot. This is not a good time to incur even "ordinary" injuries.

[Chris Chesley]

I tend to view the 'curve' more as a balloon. Push it here, it goes someplace else. Our focus on ventilators and hospital capacity is nice-- in theory, in practice it ignores the other bulges that grow everyday. Medical appointments not made, illnesses not diagnosed in a timely fashion. Many lives NOT being lost due to accidents, traffic fatalities, etc, etc. Consider also the fallout from suicide, alcoholism, domestic abuse and civil unrest.

In a perfect world, our focus on the curve sounds like it's humanitarian and noble. In practice, I am dubious that we can go into June without severe supply disruptions (despite our focus on 'essential' businesses) or unrest. The 'economy' is not faceless. It's people who are business owners, gig economy workers, service and travel industry workers, medical professionals, the whole gamut. As a business owner, if I go out of business, I am unlikely to have adequate resources to ever go back into business. I'm not alone, far too many businesses already will be unable to come back. The 'cost' is likely to be far greater than we can imagine when we are only looking at one segment of our society. The good news for me, so far, is that I've got a little longer timeline which may help our business survive.

As for ventilators? The survival rate, for those once on them, is very, very low. For me? If that time/choice were to come. I will decline the ventilator...

[kimbottles]

We got some experts here on Scantlings. This morning's article by Karl Denninger. Can you refute it?


https://www.market-ticker.org/akcs-www?post=238752

Well, I do not believe calling Birx and Fauci “clowns” is necessary to make his point.

(But I am no expert in this particular subject.)

[Jamie]

We're being very careful at home to avoid ANY injury or illness so that we don't burden the medical system right now...or have to sit in an ER waiting for treatment with sick people.

It's easy to look at quarantine as a chance to catch up on all those home projects but you've got to be careful climbing ladders, working on home electrical systems and using power tools like saws and whatnot. This is not a good time to incur even "ordinary" injuries.

Right -this is what half-baked analysis like the one posted ignore - especially avoid anything where you might have needed an ICU or ventilation. There's a good chance won't get it. We were against ACA because of "Death Panels". Unfortunately there will be here for real at the peak of the contagion.

The link posted is an argument similar in line to what the "let it run its course" school proposes. People with views like Richard Epstein at the Hoover Institute. I feel there is a Pinto-like utilitarian view of human life in there somewhere...“Pinto leaves you with that warm feeling.”

https://www.hoover.org/research/coronav ... erreaction

[SemiSalt]

I tend to view the 'curve' more as a balloon. Push it here, it goes someplace else. Our focus on ventilators and hospital capacity is nice-- in theory, in practice it ignores the other bulges that grow everyday. Medical appointments not made, illnesses not diagnosed in a timely fashion. Many lives NOT being lost due to accidents, traffic fatalities, etc, etc. Consider also the fallout from suicide, alcoholism, domestic abuse and civil unrest.

In a perfect world, our focus on the curve sounds like it's humanitarian and noble. In practice, I am dubious that we can go into June without severe supply disruptions (despite our focus on 'essential' businesses) or unrest. The 'economy' is not faceless. It's people who are business owners, gig economy workers, service and travel industry workers, medical professionals, the whole gamut. As a business owner, if I go out of business, I am unlikely to have adequate resources to ever go back into business. I'm not alone, far too many businesses already will be unable to come back. The 'cost' is likely to be far greater than we can imagine when we are only looking at one segment of our society. The good news for me, so far, is that I've got a little longer timeline which may help our business survive.

As for ventilators? The survival rate, for those once on them, is very, very low. For me? If that time/choice were to come. I will decline the ventilator...

Don't lose track of the potential. The Spanish flu killed 675,000 people in the US at a time when the population was 103 million. Coronavirus is deadlier. There is a much ballyhooed estimate of 2.2 million Covid-19 deaths if absolutely nothing was done. It was pretty much a back of envelope guess, but plausible. As it is, the top of the confidence interval is over 450,000 deaths.

The minor league statistician in me notes that the confidence limits suggest that these projections don't mean much more than 2 weeks out. I doubt that the virus is going to all but disappear by July 1. I think that's just an artifact of the model.

[kdh]

The model to me obviously assumes that isolation measures are never lifted. The width of the confidence band is about 350k cases at its greatest, with the peak happening earlier in the situations where stay-at-home measures work particularly well. Reasonable.

The model tells us something, I suppose, but not much, and the assumptions are obviously simplistic.

Just saying, "no one really knows what's going to happen" is almost as informative.

[Ajax]

What do the shaded areas represent? A "cone of uncertainty?"

[Jamie]

Yes. Distribution of possible outcomes.

Our clinical studies in China got delayed by about 2-3 months due to COVID and none of our US work can progress for the foreseeable future. That means I won't have data in time to raise money in Q3 and valuations will likely still be depressed. COVID19 means the chances of us not making it have increased a lot, even if the data comes back positive.

[kdh]

Yes. Distribution of possible outcomes.

Our clinical studies in China got delayed by about 2-3 months due to COVID and none of our US work can progress for the foreseeable future. That means I won't have data in time to raise money in Q3 and valuations will likely still be depressed. COVID19 means the chances of us not making it have increased a lot, even if the data comes back positive.

Best of luck to you and your colleagues, Jamie.

[Jamie]

Yes. Distribution of possible outcomes.

Our clinical studies in China got delayed by about 2-3 months due to COVID and none of our US work can progress for the foreseeable future. That means I won't have data in time to raise money in Q3 and valuations will likely still be depressed. COVID19 means the chances of us not making it have increased a lot, even if the data comes back positive.

Best of luck to you and your colleagues, Jamie.

Thanks. It's biotech - so how does that Doors song go? "The future's uncertain, and the end is always near".

[LarryHoward]

What do the shaded areas represent? A "cone of uncertainty?"

Yes. The size reflects uncertainty in the possible outcomes. As Keith notes, its fairly rudimentary and subject to a lot of potential input error. From observation in the Maryland numbers, small changes early in the model drive fairly significant changes in outcomes/timelines. Interestingly, the media seems to have discovered the model as it was mentioned on this morning's Today Show.

[Ajax]

Ah, very helpful. Thanks.

Jamie, I'm sorry to hear of your business difficulties.

[BeauV]

snipppp......
A note from my wife, who is tracking this stuff for her job... the new Abbott device that, per its own product insert, "Negative results do not preclude SARS-CoV-2 infection". https://ensur.invmed.com/ensur/contentA ... 55.4175589

Andy, I used to run a company in the medical field which provides a diagnostic for a medical condition. You can read about the company HERE. I am most certainly NOT a medical expert. But having gone through getting FDA (and many other) approvals, I actually know a fair bit about diagnostic tests and how they are tested.

My first comment is that I do not believe any drug or device or test in the history of US medicine has been 100% perfect. Therefore, a note like the one your wife pointed out exists for every product insert I've ever seen, it's mandatory. Please note that they use the word "preclude", meaning that a negative test with this machine does not preclude either the patient having the disease (see more on this below) or catching the disease right after the test is run.

The question, which is not addressed in the product insert, but will most likely be published later (I couldn't find it with a quick google search) is the actual rate of false-negative and false-positive diagnosis. I can tell you that all medical devices and diagnostic procedures have FDA specifications for how these are measured and those numbers are reviewed by statisticians who are WAY beyond my math skills.

As a result, I'd be shocked if there was NOT a disclaimer like this in the product insert. It would show that the insert was either a fake or that the device hadn't been through any FDA or peer review. Let's ignore the disclaimer without having the requisite back up data on the device. It's meaningless because it exists for all devices and diagnostic procedures as a defense against stupid lawsuits even in the best products.

Secondly, the most important point is not tested perfection (zero errors), the point is "Is this test useful?" In this case, usefulness is based on things like
- How many tests can it run per hour?
- How accurate are those answers?
- What alternatives do we have for this test?
- Will this test, even with its known problems, be better or worse than all the alternatives?

I think it's pretty clear that when viewed on the basis of "Is this test useful?" the answer is pretty much "Hell yes!" and the answer to "Is it perfect?" is probably "Of course not."

We're in the middle of a situation where there are quite literally no good options. I do believe we should face the fact that regardless of what we can reasonably be expected to develop in the area of testing and treatments, well over 100,000 people will die. That number is at the bottom of my own estimates, which don't matter to anyone but me. It's much more likely that we'll see 250,000 folks die, and there's an outside chance that we'll see half a million or more. That depends on how quickly humans can develop immunity and how _long_ that immunity lasts. Please keep in mind that we don't yet know if immunity is durable, although we do now appear to know that folks really to become immune for at least a couple of months.

In the midst of this "no good options" situation, I think our correct response is to take the actions which move us as rapidly in the right direction as possible. We need to avoid the traps of fantasy-thinking and hunches, which clearly ensnared Trump in late January. We also need to avoid believing there will be a silver-bullet cure; which we have no evidence of and which similar viruses don't have. In the midst of all that uncertainty and bad choices, we need to focus on the choices which suck the least. Frankly, we don't have any better options.

[BeauV]

Yes. Distribution of possible outcomes.

Our clinical studies in China got delayed by about 2-3 months due to COVID and none of our US work can progress for the foreseeable future. That means I won't have data in time to raise money in Q3 and valuations will likely still be depressed. COVID19 means the chances of us not making it have increased a lot, even if the data comes back positive.

Jamie,

I'm really sorry to hear this. I'm on some Board and we're facing this is every case. I've always thought that Cash is like Oxygen and companies are swimming from one hole in the ice on the lake to the next. If you run out of O2 between holes, you die. But, you know that. It's so incredibly difficult to take a gaggle of optimists. (Only optimists would ever even consider working at a start-up) and convince them to slow down, stop using O2, and conserve/conserve/conserve. I have a call later today to preach that to a CEO who has only cut his sales force by 5% and wants to waive quotas for the rest who haven't sold anything in a month. Needless to say, that's the wrong answer.

Good luck, my friend,

B

[Benno von Humpback]

There is no such thing as a truly binary clinical test, as far as I know. Someone will remind me of an exception, but everything I can think of measures a parameter and uses cutoff values. Then, every test has a receiver-operator curve and the user should know it. What the user also should know is the population in which those characteristics were derived. This is complicated. Many docs don't understand it (and do damage as a result, and the public understands it even less.

[SemiSalt]

What do the shaded areas represent? A "cone of uncertainty?"

Like a hurricane forecast map.

[BeauV]

We got some experts here on Scantlings. This morning's article by Karl Denninger. Can you refute it?


https://www.market-ticker.org/akcs-www?post=238752

Chris,

I'll skip any comment (but this one) about what an arrogant ass this author sounds like.

There is almost a complete lack (unless I missed something) of sources for some very outlandish claims. A quick review of claims about the survival rates of patients who have been intubated etc... shows that as written this is a massive compilation of opinions, not facts. My high school science teacher would give this paper an "F" immediately. I think my grandpa's saying applies: "Opinions are a lot like belly buttons, everyone has one and they are all useless." No citations = grade of "F".

His claim that 85% of seriously ill people is really the foundation of his argument. There is not one shred of evidence that this is true, other than this author's opinion. I can tell you that within the UCSF system, which has treated hundreds of patients, this is not true. I can't use my source here, because it was told to me in confidence. But at the very least this guy should back up his claims with sources. Otherwise... it's just a belly button (or some other part of your anatomy which my grandpa used in private).

[BeauV]

What do the shaded areas represent? A "cone of uncertainty?"

Like a hurricane forecast map.

EXACTLY (Where's my Sharpie??)

[Jamie]

Yes. Distribution of possible outcomes.

Our clinical studies in China got delayed by about 2-3 months due to COVID and none of our US work can progress for the foreseeable future. That means I won't have data in time to raise money in Q3 and valuations will likely still be depressed. COVID19 means the chances of us not making it have increased a lot, even if the data comes back positive.

Jamie,

I'm really sorry to hear this. I'm on some Board and we're facing this is every case. I've always thought that Cash is like Oxygen and companies are swimming from one hole in the ice on the lake to the next. If you run out of O2 between holes, you die. But, you know that. It's so incredibly difficult to take a gaggle of optimists. (Only optimists would ever even consider working at a start-up) and convince them to slow down, stop using O2, and conserve/conserve/conserve. I have a call later today to preach that to a CEO who has only cut his sales force by 5% and wants to waive quotas for the rest who haven't sold anything in a month. Needless to say, that's the wrong answer.

Good luck, my friend,

B

Ok, re-reading that maybe my inner-eeyor was speaking too loudly. (professional hazard - part of my job is to take the punch-bowl away before the party gets too loud)

We're not dead yet. I was very fortunate to close a round just before this all hit, but you always have to be thinking about that next round when you are clinical stage and years away from revenue. Cash is oxygen, and in our case we need enough oxygen to get our data and still leave enough so we can do a raise. It's finding that line between cutting and cutting so much that you're no longer creating value - which is our case is always about generating meaningful data to get to the next value inflection point. Let's say that the first 6 months of my tenure was doing a lot of careful, but significant, trimming because this day was coming. The good news is that due to some clever technology, and the fact we run some of them in China, we can do high quality trials for an order of magnitude less cash burn. China is back to work now, (is saying that in public tempting fate?), but Corona has pushed back my timeline enough and created enough market turmoil to make the pucker factor on my cash runway much higher than before and I never forget the consequences of getting this wrong! It's not just me.

[Slick470]

snipp...
The question, which is not addressed in the product insert, but will most likely be published later (I couldn't find it with a quick google search) is the actual rate of false-negative and false-positive diagnosis. I can tell you that all medical devices and diagnostic procedures have FDA specifications for how these are measured and those numbers are reviewed by statisticians who are WAY beyond my math skills..

I think this is the bigger issue at the moment. These numbers have been looked for, but they don't seem to be available. Without this data, the overall accuracy of the test is in question by people who need to make recommendations to people who make decisions. Maybe it's in acceptable limits, maybe it's good enough, maybe it's absolute garbage. At this point, it's hard to tell.