Coronavirus 2019-2020 thread (no unsubstantiated rumours!)

[montyp165]

The in vivo safety and efficacy portions of vaccine development have always been the biggest time bottlenecks because these portions cannot be effectively accelerated (being physiologically limited), whereas conceptual development and in vitro testing can be accelerated by computational advancements. Safety testing for vaccines via placebo is also to ensure that the excipients used in the actual vaccine do not have unanticipated reactions.

 

[superdog]

Sorry for interjecting. I think you still miss the point manqiangrexue was trying to convey.

Imo, the volunteers who got the placebo may tend to engage with riskier behavior and end up more likely getting infected compared to those in the population who know they have not got the vaccine and therefore are more careful.

How useful the result from the placebo trial, is questionable. What is for sure is that the volunteers getting the placebo may be unnecessary risking their life in the way they interact with people, thinking that they have already been vaccinated. In this sense, I tend to agree with manqiangrexue that the placebo testing may not really be that good of an idea.

In a single or double blind experiment the subject wouldn't know if they get a placebo or a vaccine, but they do know there is a chance they did not get the vaccine.

 

[manqiangrexue]

Let's say the vaccine results come in 1month faster if you decide to deliberately infect 1000-10000 volunteers (who have been vaccinated) with COVID-19, and keep them in a fully equipped hospital.

In the past month, there have been over 50,000 deaths from COVID-19, and this will probably accelerate in the coming months.

So I'd like you to try arguing against this scenario.

Actually, a human challenge trial is likely to accelerate vaccine results by close to a year because the most time-consuming phase is the final phase of observation of a large vaccinated cohort most of whom will never naturally encounter the target virus. A human challenge trial takes about 2 months and will take nowhere near 1,000 subjects as normal phase 3 can take with over a year.

Do you have experience in experimental design and human testing? If not, it's understandable you don't get it.

I do not do human testing but I have a PhD in Genetics so I am very familiar with experimental design. Putting a control group like this is exactly what I'd do if I were working with groups of mice. If I were someone volunteering for this, I would absolutely refuse to be on a placebo group because that's wasting my time. If they said it's double-blind, then this study's not for me. I need to be at least given the best chance they can muster of being successfully vaccinated, NOT brought in and jerked around with saline being pumped into my arm and blood drawn over and over again.

When you measure physiological changes in people who got the vaccine (e.g. any change to body temperature, to bodily functions, any kind of discomfort, fluctuations in various blood indications etc.), these changes are not always extreme and may only appear in a small number of your test subjects. You cannot immediately jump to the conclusion that "these changes must only be caused by the vaccine, impossible to occur otherwise". How do you know they were triggered by the vaccine, and not merely by the psychological effects of participating in the research? Or by some sampling bias/confounding conditions you overlooked during sampling and during the experimental process? Heck, even antibody tests are not always reliable, sometimes people may get false positives by infection from other coronaviruses (including the types that cause common cold), by non-infectious conditions like cancer, or by some other causes we still don't know, and it doesn't mean you're immune to COVID-19. This had been an issue in previous SARS research and could also pose a challenge in COVID-19 studies.

This is why it is standard practice to have a placebo control whenever feasible in medical research, it is always helpful to have a control group that eliminates as much confounding factors as possible. Certainly not "nothing" to be gained.

That seems like a longer version of the diplomatic response of "everything is good for something." I asked you how you would interpret data and I'll ask you again: in your placebo group, if people develop symptoms, how do you interpret that? That it's a psychological effect, or something in the vehicle, or something they got out in the world? When people in the placebo group develop anti-COVID-19 antibodies comparable to the vaccinated group, how is that interpreted?

When you're talking about potentially killing someone or cripple them for life in a human experiment you want to run, even at 0.1% probability it's not "nearly zero" but a serious safety risk to be addressed, and in most cases it is a direct "No! WTF are you thinking?" from the ethics board. Of course you may argue that some risks deserved to be taken in order to save much more lives at the end, desperate times requires desperate measures right? I'm not opposed to idea of "sacrificing for the greater good" per se. Yet the flaw in this argument is that by skipping large scale clinical trials and only test it on a few dozen "young and healthy, artificially infected" subjects, you run a high risk of omitting serious side effects. In addition, you cannot confirm the efficacy of the vaccine on those who are not so young, not so healthy, or those who appeared young and healthy but contacted a higher dose/different strain of the virus than your highly limited artificial infection sample. I believe it's a bad idea to skip standard phase 3, so intentionally infecting small samples at an earlier phase becomes an unnecessary risk.

We have to remember that a vaccine not properly tested for side effects can kill a lot of people directly, and a vaccine that's only partially effective but thought to be completely effective can kill a lot of people indirectly (by putting millions of people back to high risk environments thinking they have immunity when many do not). There is a reason the USA, China and other countries are not planning to skip large scale trials, it is not because they couldn't find brave subjects willing to face sub-percentile risk of dying.

Well, if the "ethics committee" gives it a "WTF are you thinking," then they can go home, open up the Corona tracker web-page and watch those casualty numbers surge by the hour like they're watching TV and we'll see what they're thinking. Consenting adults who knew the very low risks were willing to reduce that ticker by over a year but the "ethics committee" vetoed that so now they've got the Corona Show running 4 more seasons for them to watch.

The human challenge trial can still have different doses of viral challenge as well as vaccination. That old, immuno-compromised people may not benefit as much from anything is a concept that's prevalent everywhere in medicine. But there are many people who can benefit from a human challenge trial if it can bring out even a semi-effective vaccine in short order. This can be run in tandem with the regular phase 3, but in the mean time, if it's determined to be safe for everyone in a regular phase 2, and effective by a human challenge trial, then having it now is much better than not having anything until the phase 3 is done 12-18 months down the line.

 

[supercat]

The data from New York metro area continue to be a mess. So I will post those for one last time today.

Cases:	98,715
Total hospitalized*:	27,457
NYC confirmed deaths:	5,742
As of:	April 11, 5 p.m.

*Estimated.

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Situation in the U.S. on April 11 at 8:00 pm EDT:

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On April 11, excluding Hong Kong, Macau, and Taiwan, there are 2 domestic and 97 imported new cases. There are 63 new asymptomatic cases. There are 49 new suspected cases, all imported. There is no death nationwide. There are 77,575 cured cases and 1,138 existing cases. Existing cases in Hong Kong and Macau decreased 16 to 695.

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[superdog]

Actually, a human challenge trial is likely to accelerate vaccine results by close to a year because the most time-consuming phase is the final phase of observation of a large vaccinated cohort most of whom will never naturally encounter the target virus. A human challenge trial takes about 2 months and will take nowhere near 1,000 subjects as normal phase 3 can take with over a year.

I do not do human testing but I have a PhD in Genetics so I am very familiar with experimental design. Putting a control group like this is exactly what I'd do if I were working with groups of mice. If I were someone volunteering for this, I would absolutely refuse to be on a placebo group because that's wasting my time. If they said it's double-blind, then this study's not for me. I need to be at least given the best chance they can muster of being successfully vaccinated, NOT brought in and jerked around with saline being pumped into my arm and blood drawn over and over again.

That seems like a longer version of the diplomatic response of "everything is good for something." I asked you how you would interpret data and I'll ask you again: in your placebo group, if people develop symptoms, how do you interpret that? That it's a psychological effect, or something in the vehicle, or something they got out in the world? When people in the placebo group develop anti-COVID-19 antibodies comparable to the vaccinated group, how is that interpreted?

Why are you so fixated on interpreting data from a placebo group as if that is some stand-alone sample? If some symptoms are observed in the placebo group, this is an indication that similar levels of symptoms you observed in the vaccine group cannot be attributed to the vaccine. If people in the placebo group tested positive for COVID-19 related antibodies (at a significantly higher rate than what you'd expect from population average), then you should take a serious look at possible sample contamination, unaddressed bias (on prior exposure to COVID-19) in your sampling method, and the reliability of your antibody testing methods especially on false positives, all of which could seriously threaten the validity of your clinical conclusion. Without a placebo group, you simply wouldn't know something's wrong. So no matter how you look at it, having a placebo group provides valuable data and helps you reach more reliable conclusions.

This is very basic stuff. If you received professional training in experimental design, you should know better.

Well, if the "ethics committee" gives it a "WTF are you thinking," then they can go home, open up the Corona tracker web-page and watch those casualty numbers surge by the hour like they're watching TV and we'll see what they're thinking. Consenting adults who knew the very low risks were willing to reduce that ticker by over a year but the "ethics committee" vetoed that so now they've got the Corona Show running 4 more seasons for them to watch.

The human challenge trial can still have different doses of viral challenge as well as vaccination. That old, immuno-compromised people may not benefit as much from anything is a concept that's prevalent everywhere in medicine. But there are many people who can benefit from a human challenge trial if it can bring out even a semi-effective vaccine in short order. This can be run in tandem with the regular phase 3, but in the mean time, if it's determined to be safe for everyone in a regular phase 2, and effective by a human challenge trial, then having it now is much better than not having anything until the phase 3 is done 12-18 months down the line.

I've said in the previous post and I will say again, a standard phase 3 in vaccine development, despite time-consuming, is necessary not because we are too much of a coward to test vaccinate and infect a few dozen people, but because an unsafe or unreliable vaccine has the potential to kill even more people than if we waited without one. Not to mention the sociopsychological impact it'd do to the populace on their acceptance of further vaccination.

 

[Blitzo]

Yeah I really don't see why a placebo group is causing such a heated discussion tbh, it's pretty much standard when evaluating basically any new treatment.

Also, the point of being a volunteer for this kind of study isn't for you to get the experimental vaccine and potentially achieve immunity, because that basically means you're doing so for selfish reasons -- the entire point is that you're volunteering your body for the sake of a research method that might produce results that can benefit the entire population at large, once the various trial stages are eventually completed.

 

[Dolcevita]

Yeah I really don't see why a placebo group is causing such a heated discussion tbh, it's pretty much standard when evaluating basically any new treatment.

Also, the point of being a volunteer for this kind of study isn't for you to get the experimental vaccine and potentially achieve immunity, because that basically means you're doing so for selfish reasons -- the entire point is that you're volunteering your body for the sake of a research method that might produce results that can benefit the entire population at large, once the various trial stages are eventually completed.

LOL. Also, it is NOT LIKELY THEY WILL TELL the volunteers who is getting the the placebo and who is not. The point of the trial to minimize or eliminate false psychological findings from the result.

I did not read all the post but I just want to post this here just in case someone is missing the point

If all the volunteers reported they are suffering from severe head-ache as a result of treatment, they can deduce that it could not be possibly true for those who got the placebo and it was likely because of some psychological effect on how the trial was conducted. Further trials will need to be conducted to eliminate the psychological factor.

If only non-placebo volunteers reported head-ache, then researchers know it is a side-effect.

Hence, the reason on why there needs to be placebo group.
Anyone who absolutely refuse to be in a placebo group should not be in included in the Trial.

Again, no conclusion on whether it is effective treatment to COVID-19 or not as none of the volunteers are infected.

 

[Blitzo]

LOL. Also, it is NOT LIKELY THEY WILL TELL the volunteers who is getting the the placebo and who is not. The point of the trial to minimize or eliminate false psychological findings from the result.

I did not read all the post but I just want to post this here just in case someone is missing the point

If all the volunteers reported they are suffering from severe head-ache as a result of treatment, they can deduce that it could not be possibly true for those who got the placebo and it was likely because of some psychological effect on how the trial was conducted. Further trials will need to be conducted to eliminate the psychological factor.

If only non-placebo volunteers reported head-ache, then researchers know it is a side-effect.

Again, no conclusion on whether it is effective treatment to COVID-19 or not as non of the volunteers are infected.

Yeah, the whole point of a placebo is that the participants are not informed what they're receiving.

It's not like participants can simply "refuse" to be in the placebo group as mentioned by manqiang in a previous post -- but rather if the trial is designed even half competently they should be randomly allocated and appropriately blinded..

 

[manqiangrexue]

Why are you so fixated on interpreting data from a placebo group as if that is some stand-alone sample?

Because if you cannot interpret the data from a group, then what good is the group?

If some symptoms are observed in the placebo group, this is an indication that similar levels of symptoms you observed in the vaccine group cannot be attributed to the vaccine.

Not that these people were infected and exposed to different things in their daily lives?

If people in the placebo group tested positive for COVID-19 related antibodies (at a significantly higher rate than what you'd expect from population average), then you should take a serious look at possible sample contamination, unaddressed bias (on prior exposure to COVID-19) in your sampling method, and the reliability of your antibody testing methods especially on false positives, all of which could seriously threaten the validity of your clinical conclusion.

So if some of your placebo group got naturally infected during the course of the 12-18 month phase 3 and naturally developed antibodies, that invalidates your vaccine or shows contamination in your study?

Without a placebo group, you simply wouldn't know something's wrong. So no matter how you look at it, having a placebo group provides valuable data and helps you reach more reliable conclusions.

With a placebo group that yields uninterpretable data, you still don't know what's wrong and basically have to explain away everything you see. If the placebo group developed antibodies, then it's because they developed them naturally; if they got sick, then it's because they got exposed to something, etc...

Human challenge trials lasting 2 months in a secure facility solves all of these issues.

This is very basic stuff. If you received professional training in experimental design, you should know better.

For mice, it's basic. For people, you need to think instead of opening a textbook, reading that you need control group, so you do a control group. For me, a person, it's disrespectful to haul my ass into the hospital to get my blood time and time again after injecting me with saline when you have something that can potentially vaccinate me.

I've said in the previous post and I will say again, a standard phase 3 in vaccine development, despite time-consuming, is necessary not because we are too much of a coward to test vaccinate and infect a few dozen people, but because an unsafe or unreliable vaccine has the potential to kill even more people than if we waited without one. Not to mention the sociopsychological impact it'd do to the populace on their acceptance of further vaccination.

I didn't say the phase 3 needs to be nixed; I said human challenge trial can be done in parallel to get something out there ASAP. Safety is already established in phase 2, which is pre-human challenge trial. Reliability will be determined in the human challenge trial, over a smaller but controlled group. In the meantime, it's better to have something that at least partially works (or completely) than to have nothing at all until phase 3 ends in 12-18 months.

I simply do not agree with you or Bltzio that this is a standard case that defaults to the textbook approach to experimentation. I think this is a very urgent situation and executive decisions need to be made to speed things up drastically.

 

[antiterror13]

Many Americans go to work even when they are sick - because they have no alternative.

The USA are opening up their country even though they don't have Covid-19 under control yet - because they have no alternative.

Happy are those who live in a country that can afford a different approach to a pandemic.

In a way most Americans are really poor, live from paycheck to paycheck. The government don't support them, unlike NZ, Aus, UK and and most EU nations