TLS Guy

TLS Guy

Audioholic Slumlord
As you already know, I oppose this idea. My reason, however, is not because of any personal adherence to medical ethics – I'm not a physician – and I never took the Hippocratic Oath.

It would be wrong to abandon the high standards of clinical trial-based evidence that the US FDA requires. If we do it now because of the SARS-CoV-2 pandemic emergency, we will regret it in the future. These high standards have been the result of hard lessons learned in the past when those standards were lower, or did not yet exist. I can think of two examples: Thalidomide and the Polio Vaccine.

Thalidomide led to a major change in law in both the USA and the UK.
https://en.wikipedia.org/wiki/Thalidomide_scandal#Change_in_drug_regulations

Fortunately, the Polio Vaccine story seems to have ended well. Although the SV40 tumor virus contamination created a real scare, enough time has passed to realize it was probably harmless. In fact, few people outside of biomedical science even know about it.

Both episodes resulted in a genuine tightening of laws and regulations for testing drugs. They led to a carefully worked out and more rigorous system of testing for safety and efficacy for new drugs that remain as the gold standard.

In more recent times, I can remember when Interferon was said to be a magic bullet against cancer. It was the first gene product to be manufactured by recombinant DNA methods and was revolutionary for the drug industry in the 1990s. It was widely tested against a number of cancer types, and was reported to have significant positive effects against colon cancer. I recall at least six clinical trials reporting that. Unfortunately, these trials were the small Phase 2 trials. There were not enough patients to allow genuinely significant results, and many of them did not include a control arm where similar colon cancer patients were tested with standard therapy only.

Years later, three very large Phase 3 trials were completed, in North America (USA plus Canada), Asia, and Europe (all the EU plus the UK). All of them produced negative results – Interferon was not effective against colon cancer, and it was significantly toxic when given at the high doses used in the trials. Before those results were available, many oncologist were clamoring for early approval of Interferon. After it was found to be ineffective, the overwhelming opinion among oncologists was that they were glad Interferon was not given an early approval. In fact, the whole Interferon episode was said to be a good example why we must do those large and time consuming Phase 3 clinical trials.
https://en.wikipedia.org/wiki/Interferon#Interferon_therapy

The bottom line – wait for the results of properly designed large Phase 3 clinical trials. Don't allow panic to bust the drug testing & approval system. We worked very hard in the past to get it as good as it is now.
I'm sorry, but we have to think out of the box on this one. Populations are just not going to put up with these onerous containment measures much longer. You can see them breaking apart quite rapidly. Frankly, the world's economy can not take this much longer, certainly not until 2022. Academics can rave all they want, but I'm telling you that is not going to stop a different approach here. I know most practicing, and retired physicians view this way the same way I do. The ICU staff can not keep up this pace any longer world wide. They are seriously run down and will start quitting in increasing numbers.

That is why I strongly favor going to viral challenge studies. That will tell us above all effectiveness and a lot about safety. We are just not going to be able to go for the level of safety we normally do here. There are just too many deaths, permanent injury and economic disruption. We really do need to approach this with a war mentality.

So, if Trump and Boris Johnson and others force the issue on this one, they will have my support. I can tell you right now, dragging this out until 2022 by slavishly adhering to usual protocol is not going to happen, and nor should it, otherwise needless lives will be lost.
 
Swerd

Swerd

Audioholic Spartan
The NYT is reporting the first documented case of a person being reinfected. The fact that it was only 4.5 months after the first infection is not exactly comforting. On the other hand, he had no symptoms the second time so that may be some good news.

I realize one case doesn't say much about how common it may be, but it does show it's possible.

>>>“An apparently young and healthy patient had a second case of Covid-19 infection which was diagnosed 4.5 months after the first episode,” University of Hong Kong researchers said Monday in a statement. . . . The 33-year-old man had only mild symptoms the first time, and no symptoms this time around. . . . Doctors have reported several cases of presumed reinfection in the United States and elsewhere, but none of those cases have been confirmed with rigorous testing. Recovered people are known to shed viral fragments for weeks, which can cause tests to show a positive result in the absence of live virus.

But the Hong Kong researchers sequenced the virus from both rounds of infection and found significant differences in the two sets of virus, suggesting that the patient was infected a second time.<<<

I think it's worth pointing out that we have never had such sensitive methods of detecting a virus before.

The fact that this person didn't know he was infected the second time and had no COVID-19 symptoms is consistent with how immunization works. It doesn't prevent you from being re-infected by the virus, but it will limit the infection enough to prevent you from getting sick.

That's a strong argument in favor of vaccination.
 
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M

Mr._Clark

Full Audioholic
I just found this article by Nassim Nicholas Taleb about face masks.

He makes several very good points with regards to math and statistics (I'd concede that the non-aggression principle is philosophical and not subject to formulation as a testable hypothosis)

 
M

Mr._Clark

Full Audioholic

Too few people in the trial to say anything, IMO, but Moderna yaps about anything positive.
It's better than a complete flop. I've have yet to find any actual numbers in terms of the immune response. Most news blurbs refer to a "similar" response as younger test subjects, but that is a fuzzy term. The closest I have found so far is the following:

"Additionally, the antibodies that were produced were higher than those seen in people who have recovered from Covid-19."

Presumably "higher" doesn't refer to the effects of weed (yes, that was a lame attempt at humor).
 
Swerd

Swerd

Audioholic Spartan

Too few people in the trial to say anything, IMO, but Moderna yaps about anything positive.
The only interesting thing about that press release was that two older age groups, 56-70 years old and 71 and older, were tested. 10 people in each group. They concluded the vaccine seemed like it worked, but no data was shown. No serious adverse reactions were mentioned.

Typically when medications and vaccines are tested, the age group of 55 years old or less, gets approved first because large numbers of that age group are more readily available. The FDA considers older than 55 and older than 70 as separate age groups that have different safety and efficacy requirements. They will also take longer to accrue enough people for statistically significant results. So, they are tested separately from the 55 years and younger age group. Moderna is simply complying with the FDA's usual requirements.

Moderna's press release is best thought of as a preliminary (not yet published) report of a Phase 1 test for safety in those two older age groups. Based on results, they will proceed with Phase 3 clinical trials, vaccinating enough people from those two older age groups to allow conclusive results. Moderna already has a large Phase 3 trial underway of people age 55 and younger. If successful, it will lead to approval only for that age group. The older age groups must wait until separate trials are finished.
 
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TLS Guy

TLS Guy

Audioholic Slumlord
Things seem to be moving fast on the vaccine front in the UK.

According to the UK's deputy medical officer professor Jonathan Van-Tam, the UK regulator MHRA, the equivalent of our FDA, may well be able to grant temporary use authorization for distribution of the Oxford vaccine as early as October. So that means within two months.

I watched the BBC news at six today, and arrangements to distribute the vaccine are getting into high gear. In addition to allowing doctors and nurses to administer the vaccine, dentists and even vets are being trained.

So this nightmare will end sooner than we think. I suspect for Professor Van-Tam to make a statement like this has to mean they have very strong signals from their phase III trials already, which started some time ago in Brazil and India. It seems to me that enough time has passed since this trial started that there has been enough time to judge safety and effectiveness.

The UK government threw another 6 million pounds sterling at this today, to better understand the induced immunity, especially its duration.

I understand that the UK government are starting to signal that cinemas, theaters and concert halls, may be able to fully reopen sometime between November and January. At the moment the restrictions have been so onerous they have remained closed.

The question will be how soon will it be available in the US. I have not heard of any well thought out plans to distribute in yet, and it is not too soon to start. We have already had far more Covid-19 deaths than would should have had. We don't want more by fumbling the distribution of a vaccine.
 
Irvrobinson

Irvrobinson

Audioholic Spartan
The question will be how soon will it be available in the US. I have not heard of any well thought out plans to distribute in yet, and it is not too soon to start. We have already had far more Covid-19 deaths than would should have had. We don't want more by fumbling the distribution of a vaccine.
US distribution planning is starting, but I'm sure we'll be behind a lot of countries. One issue is the sheer magnitude of the problem, with 326M people over such a large geographic area, and our widespread phobic anti-vaccination cult. I know more than a few rational people who are wondering if Trump is compromising FDA decision-making, so they're having doubts too. Here's what the Washington Post says:


Edit: it is interesting to read comments on the WP web site at the end of the article. Many vaccination phobia comments. Bozos.
 
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TLS Guy

TLS Guy

Audioholic Slumlord
US distribution planning is starting, but I'm sure we'll be behind a lot of countries. One issue is the sheer magnitude of the problem, with 326M people over such a large geographic area, and our widespread phobic anti-vaccination cult. I know more than a few more rational people who are wondering if Trump is compromising FDA decision-making, so they're having doubts too. Here's what the Washington Post says:


Edit: it is interesting to read comments on the WP web site at the end of the article. Many vaccination phobia comments. Bozos.
I'm not sure what the storage temperature of the Oxford vaccine is. The most frail are the mRNA vaccines, like Moderna and Pfizer. Those vaccines require -80 Celsius. I came across this article about UPS building freezer farms at airport hubs.



I think we are now approaching the exciting time in this crisis and will be watching an enormous outbreak of human creativity.

Astazeneca say they are producing 400 million doses of the Oxford vaccine for Europe. No word on what the production will be for the US, or from where.

India is already producing the vaccine, but not rolling it out. I expect it will be at the time the UK give it approval.

Unfortunately no one in the US has stepped up to produce the Oxford vaccine at risk. This may well prove to be a costly oversight in the US.
 
TLS Guy

TLS Guy

Audioholic Slumlord
Yes, I know that. However Astrazeneca is a UK company and as far as I know have no US production facilities. They have built the factory for the Oxford vaccine in Holland I believe. So 400 million for Europe and 300 million for the US, is 700 million all told. That is a huge stretch for one manufacturer. That is a really unlikely to happen in my view, especially as the Oxford vaccine requires massive culture of the non replicating monkey adenovirus as the vector.

The Indian plant is going to be the bigger one, but as I understand it the billionaire owner wants his production to go preferentially to third world nations. I still think it will prove to be a failing not to have built a plant for the Oxford vaccine in the US. May be someone has, but if so they have kept very quiet about it.
 
M

Mr._Clark

Full Audioholic
Hopefully this is just a fluke:

>>>What caught experts’ attention about the case of the 25-year-old Reno man was not that he appears to have contracted SARS-CoV-2 (the name of the virus that causes Covid-19) a second time. Rather, it’s that his second bout was more serious than his first.<<<

 
Swerd

Swerd

Audioholic Spartan
@Irvrobinson and @TLS Guy

I didn't know about the -80° freezer requirement for the mRNA vaccines. That will be a big expense, and will limit the how the vaccine is transported and stored in the hinterlands. Either I didn't think of it, or I imagined they included lipid/protein capsids that protect the mRNA.

There are two types of medical/laboratory freezers in common use. The more expensive -80°C deep freezers use 2-stage compressors, and the -30°C freezers use single stage compressors. The -30° freezers are similar to what we have in our kitchens, but they have no auto-defrost in them.

Does the adenovirus based Oxford vaccine require freezing of some kind? Vaccines best suited for use in 3rd world countries in Africa and Asia don't require freezing at all. The vaccination material is lyophilized (freeze-dried) in individual vials, and reconstituted with water-for-injection just before use. Of course, getting that developed is also time consuming and expensive.
 
TLS Guy

TLS Guy

Audioholic Slumlord
@Irvrobinson and @TLS Guy

I didn't know about the -80° freezer requirement for the mRNA vaccines. That will be a big expense, and will limit the how the vaccine is transported and stored in the hinterlands. Either I didn't think of it, or I imagined they included lipid/protein capsids that protect the mRNA.

There are two types of medical/laboratory freezers in common use. The more expensive -80°C deep freezers use 2-stage compressors, and the -30°C freezers use single stage compressors. The -30° freezers are similar to what we have in our kitchens, but they have no auto-defrost in them.

Does the adenovirus based Oxford vaccine require freezing of some kind? Vaccines best suited for use in 3rd world countries in Africa and Asia don't require freezing at all. The vaccination material is lyophilized (freeze-dried) in individual vials, and reconstituted with water-for-injection just before use. Of course, getting that developed is also time consuming and expensive.
I do not know if the Oxford vaccine requires freezing. I suspect it will, but I certainly don't know that. The plan in the US as I understand it is to put UPS in charge. They are planning these huge freezers at airport hubs and then delivering by air with dry ice. So the vaccines will need to be administered soon after delivery. This will require very precise logistics and appointment scheduling. They should be able to lease planes really cheap! There are also a lot of out of work pilots.
 
Irvrobinson

Irvrobinson

Audioholic Spartan
I do not know if the Oxford vaccine requires freezing. I suspect it will, but I certainly don't know that. The plan in the US as I understand it is to put UPS in charge. They are planning these huge freezers at airport hubs and then delivering by air with dry ice. So the vaccines will need to be administered soon after delivery. This will require very precise logistics and appointment scheduling. They should be able to lease planes really cheap! There are also a lot of out of work pilots.
From what I've read it's only the mRNA vaccines that need such low temperatures. Here's a WSJ article that complements the one Mark posted, but note it does require a subscription to read (I think):

 
TLS Guy

TLS Guy

Audioholic Slumlord

Watch your kidneys.....
Kidney damage from this virus has been known from the outset. Covid-19 in its essence is an infectious vasculitis. That makes it unique in infectious diseases. There has never been one before, and this makes this infection especially dangerous. You see its primary target is blood vessels. There are blood vessels all over the body. However some organs, and especially kidneys are vulnerable to all causes of vasculatis. Often times in vasculitis, it is kidney failure that brings the process to attention.
 
TLS Guy

TLS Guy

Audioholic Slumlord
Not me:

As stated above, the UK is taking the same line and moving to emergency approval. Under the circumstances this is entirely reasonable.

Already this pandemic has extracted a dreadful cost, in death, misery, disability, economically and educationally. Attempts to reopen schools, sporting events, and especially universities are not going well. The UK in particular has reached the barriers of what it can do financially to prevent extreme misery to the population.

In addition, many feel that the worst is yet to come without a more aggressive approach. As the weather cools people will come inside, and Covid-19 infections coincide with influenza infections. A paper published in JAMA Saturday, looking at co-infection in China, showed this not to be rare at all, and increased mortality by 18%. So everyone should get their flu vaccine as soon as it is released.

I think as soon as there are signals that the vaccine has a low incidence of side effects, and is effective, then this needs to be rolled out quickly on an emergency basis.

I do see there may be some conflicts between practicing physicians, and academic/regulating ones. However practicing physicians are used to balancing difficult risk/benefits throughout their careers. Certainly I had to make these calls in occasions and take unapproved lines of action.

The fact is that as soon as there a clear signals, and I strongly suspect that those signals are there, that a vaccine presents far lower risk to health than the virus it should be rolled out.

At that point then clear guidance should be given, with as accurate a time line as possible. If a vaccine can start rolling out in quantity within two months say, then I think it would quell risky behavior like the reopening of universities and schools when the R value is too high to safely do so.

As soon as it is clear that rolling out the vaccine is less risk than the virus, then it needs to rolled out promptly. This is not a normal vaccine roll out. These are not ordinary times, so following established protocols will lead to greater disaster.
 
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