The Medical Thread: Vaccine Search / Staying Healthy / Treatments Etc

sk8pics

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Yeah, there is a lot of reason to be skeptical of that original study. It contained very few patients. Patients were excluded from the hydroxychloroquine arm who really should have counted as failures. And I have yet to find a good scientific reason for how azithromycin got involved at all. (If anyone sees anything, point me to it, because i really want to know why there is an antibiotic being used to treat this *****.)

That being said, the new study doesn't show much either. It's an observational study, not a randomized control trial, so it's entirely possible that doctors are giving hydroxychloroquine to patients they view as the most serious which results in a higher death rate. It's also possible that the side effects from hydroxychloroquine actually are resulting in a higher death rate. But there's no way to know from that study.
Yes, I agree with you. The authors of that original study annoy me to no end for exactly the reasons you state, they threw out data that perhaps should not have been thrown out. And yes, the new study is not without flaws either. My main point, though, was that the NIH site was updated just yesterday with new info, and specifically recommending against the combination of drugs that was being given to my aunt.
 

BlueRidge

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What do science/medicine knowledgeable folks think of this?:

United States should allow volunteers to be infected with ******** to test vaccines, lawmakers argue (Science magazine)

Political support is building for regulators in the United States to embrace the controversial strategy of intentionally infecting volunteers with the ***** that causes *********-19 in order to test experimental vaccines. Such human challenge trials could greatly accelerate the development of an effective vaccine, 35 members of the House of Representatives argue in a letter sent yesterday to the heads of the U.S. Food and Drug Administration (FDA) and its parent agency, the Department of Health and Human Services (HHS).

“[A] more risk-tolerant development process is likely appropriate in the case of a *********-19 vaccine,” write the group of lawmakers, which includes both Democrats and Republicans. “The enormous human cost of the *********-19 epidemic alters the optimization of the risk/benefit analysis.”

...In theory, challenge trials could enroll volunteers who are at low risk of harm from the ***** that causes *********-19—dubbed SARS-CoV-2—such as young adults who rarely develop serious symptoms after becoming infected naturally. “Our situation in this ********* is analogous to war, in which there is a long tradition of volunteers risking their health and lives on dangerous missions for which they understand the risks and are willing to do so in order to help save the lives of others,” the letter states. “Every week of delay in the deployment of a vaccine to the seven billion humans on Earth will cost thousands of lives.”
 

Impromptu

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Studies using healthy volunteers are used to test a multitude of treatments (and depending on what the treatment is for, is sometimes even required prior to the treatment being tested in sick patients - we had a trial last year that the FDA requested we test in healthy volunteers, prior to testing in cancer patients). As long as the volunteers are appropriately consented as to the risk, and as long as you can show that you're not offering undue pressure for them to enroll (e.g. undue pressure could even be going into a community with a high poverty level and offering them $1000 dollars to enroll on the trial)... anyway, I could segue into a lot of regulatory law, but bottom line, is that in general, healthy volunteers are permitted as long as you are doing your absolute best to inform them of and protect them from risk.

There is a lot of FDA guidance on vaccine trial development here, if you want to slog through the legalese:

It looks like the bigger issue is the question of using a "human challenge" model (and I think the Science article may be overly simplifying the experimental plan), but there are regulatory pathways available for this model.

Are you able to access this article here: https://www.sciencedirect.com/science/article/pii/S0264410X19307704?via=ihub (I'm using my work VPN which can access a lot more medical data than otherwise, so I am never sure if I am linking to something that viewable)?

Anyway, if you can't get to the article, here are some quick clips from it:

Because the potential benefits and risks of controlled human infection studies can be variable and dependent on specific details, it is rarely useful or appropriate to conclude a priori that broad categories of CHIM studies are ethical (or unethical). FDA’s approach to the evaluation of CHIM study proposals is case-specific. When proposals to conduct controlled human infection studies under US IND raise ethical issues, FDA may consult with medical ethicists as appropriate. While safety is the primary consideration, and action (e.g., clinical hold) may be necessary if risks to subjects are unreasonable and significant, FDA is committed to working with investigators to identify and establish safety surveillance and risk mitigation strategies that enable controlled human infection studies to proceed when scientifically and ethically justified, and with appropriate subject protections.

In the US, CHIM studies are required to be conducted under IND. Federal regulations regarding the safety and protection of human subjects apply to these studies. Systematic monitoring, recording, and reporting of safety data following challenge is an important aspect of conducting CHIM studies. CHIMs can enhance development of an investigational vaccine at various stages during development. The decision to develop a CHIM to provide primary or supportive evidence of effectiveness of a product may depend on the feasibility of conducting a field efficacy study and on the strengths and limitations of the challenge model. Because of the complex considerations related to the use of CHIMs to support development of investigational vaccines, early and frequent interactions between FDA and vaccine sponsors are crucial to enhance efficient product development.

Anyway, my take is that there are precedents for this kind of model, and regulatory pathways and regulations in place, but I hope that there would be oversight to make sure those regulations (starting from trial design through actual conducting of the study and follow-up) were being followed in any study using this model.

I've worked with with investigators to help get their trials approved by the FDA (caveat, this was with cancer studies, prior to all of this crud happening... although I'm working now with an investigator on a crud treatment, so I'll have a better idea in about a month how closely they are looking at ***** treatments) and I've been through a couple FDA audits and under normal circumstances, the rules and regulations are extremely thorough.

Unfortunately, these aren't normal times.
 

aka_gerbil

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With animal vaccines, USDA requires challenge studies in order to demonstrate protective efficacy and illness mitigation as part of licensing. (Done once, then subsequent serials are evaluated for potency against the serial used for the trial.) I’m not as well versed on whether this is typical or a requirement for human vaccines.

My understanding is that FDA requirements are even more strict than USDA requirements, which are very strict on their own.
 
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BlueRidge

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thanks @Impromptu that's helpful. The Science article didn't really discuss much more than the letter from the members of Congress, and I had to wonder about politicians advocating on this, so this is interesting to see more about. (I can only access the abstract for the link you posted.)
 

Theatregirl1122

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With animal vaccines, we are required to do challenge studies in order to demonstrate protective efficacy and illness mitigation. I’m not as well versed on whether this is typical or a requirement for human vaccines.

Challenge studies in humans are not common in vaccine development which is why the push to do so in this case is highly controversial. For example, most major vaccines, such as Polio and measles, were developed and approved without any kind of challenge study.

Yes, using healthy volunteers is common in medical research, but they are not normally volunteering to be infected with a deadly disease. Not all things in ethics follow the principal that if the subjects consent, it is ethical. Some things doctors will not do, even with your consent, and many consider deliberately infecting a healthy person with a serious disease to be one of those things.

The issue at hand is that vaccines can be developed without challenge studies. They can be developed faster with challenge studies. But the medical establishment also lives by the principal “first, do no harm.” So at what point does the end justify the means? It’s not a trivial question.
 

aka_gerbil

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Thanks. My knowledge of specifics in vaccine testing and licensing and what is required and standard practice is limited to those for veterinary use, which are regulated by an entirely different agency (USDA vs FDA).

Maybe the middle ground here is non-primate humans. I know a lot of people don’t like animal research, particularly in non-human primates, but they are our closest relatives with a highly similar immune system.
 

missing

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Nathan Leopold (of Leopold and Loeb) was one of many prisoners who agreed to be infected with malaria to help find treatments (with the hope of getting prison sentences lowered):

Leopold was still serving his sentence, at the age of 39, when the malaria experiments began at Stateville. He volunteered, beginning as a test subject.

Leopold underwent inoculation by mosquito vector, developed malaria symptoms, and served as a case study for several anti-malarial treatments and drugs. He continued in the experiment through its end, in a variety of additional roles, including recruiting new volunteers. Leopold also served as an observer to validate experiments, and dissected mosquitoes under supervision.
 

MacMadame

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I suspect we don't need to challenge studies to get a vaccine. Which is probably why this push is coming from politicians and not scientists.
 

aka_gerbil

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I suspect we don't need to challenge studies to get a vaccine. Which is probably why this push is coming from politicians and not scientists.

Speaking as a scientist, objectively, challenge studies are a faster way to get efficacy data than vaccinating and following a cohort. With a challenge, you have more control over conditions, specific test groups, knowing the subjects have been exposed to the pathogen. Otherwise, you’re just following a cohort over time to see what happens. If this were a ***** infecting chickens, for example, and not humans.... we’d do the challenge study (and we’d have to to get the vaccine fully licensed).

It’s really a question of human medical ethics. Is it better to let some humans take the risk to get the data faster or is it something we shouldn’t ask of people because of the risk? I don’t have an answer to that.
 

clairecloutier

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Here is an article from Bill Gates providing a general survey of the current state of the science around BB. He addresses testing, antibody testing, treatments, vaccines, reopening procedures. It's a bit long (24 min), but worth the time IMO.

 

canbelto

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Hedwig

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the head virologist of Germany, Christian Drosten, yesterday talked in his podcast about a possible vaccine coming from China. He sounded doubtful but I thought everything he said sounded quite hopeful (but maybe I just WANT to be hopeful).
Any articles about his in the english speaking news?

it is a dead vaccine which according to him can have problems in that it may even worsen symptoms. in this case, trials with apes have been very good indeed. even while injecting tons and tons of the ***** in their lungs they still did not get sick and they could tolerate the vaccine very well.
 

mjb52

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I find the presentation of this somewhat misleading - to me the articles make it sound like they are saying it doesn't do so, which is not accurate. They are saying something else, that the issue hasn't been studied sufficiently yet to know whether or not it does. You can find their actual scientific brief here: https://tinyurl.com/yah6dvnp
 

acraven

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@Hedwig, I have been watching a lot of ******** news on CNN--which is focusing on that topic extremely heavily. I haven't heard anything about that Chinese vaccine (though I could certainly have missed it). The four rather promising vaccine-related reports I've heard over the last week or so involved these:

- NIH (US) vaccine that officials hope to have available for medical people by this fall.
- Oxford University (UK) vaccine that an official was 80% confident about and hopes to have available for early users (medical people again, I assume) this fall.

It sounded to me as if both of those might be intending the early vaccine use within the medical world as a sort of large-scale test, though I may have misinterpreted that. I believe both are thinking of wider availability during the spring of 2021, and the interviewees spoke of ramping up production earlier in the process than would normally be the practice.

CNN also reported on two existing vaccines proponents hope may have some preventive value. They could and perhaps help bridge this period, at least for health-care workers, before a ********-specific vaccine is available:

- There's a substantial quantity of an old TB vaccine stockpiled in Germany, according to a scientist from the Max Planck Institute.

- There's also a large supply of an old vaccine stored in the US (I think in Texas). This might be a smallpox vaccine, but I'm not confident about that.

Obviously, it's possible that none of the above will pan out.
 

aka_gerbil

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I find the presentation of this somewhat misleading - to me the articles make it sound like they are saying it doesn't do so, which is not accurate. They are saying something else, that the issue hasn't been studied sufficiently yet to know whether or not it does. You can find their actual scientific brief here: https://tinyurl.com/yah6dvnp

Yeah. As a scientist currently working in vaccines and immunology, I get what they’re getting at and why. However, what they’re saying isn’t what the standard press and therefore general public are reading it as and, IMO, it’s causing unnecessary panic and anxiety.

What they are saying right now is that the research has not been completed yet to demonstrate protective immunity. It doesn’t mean that getting this doesn’t confer long term protective immunity. It means we don’t know yet and therefore policy based on the assumption that having antibodies does indeed confer protective immunity is not wise at this point because it hasn’t been fully studied yet.

Based on the crud’s closest relatives of original crud and Middle Eastern crud, I and every other immunologist I know is going to be shocked if infections at and above a certain threshold so not confer protective immunity. But, we have to do the studies with the crud itself before setting policy and not just make policy off of assumptions.
 

mjb52

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I actually unsubscribed from the Washington Post yesterday because I was so tired of this kind of thing (in relation to a different article). Given the psychological stress people are under already, it is just grossly irresponsible. It's not just them, but at least I felt like I was doing one small thing to protest against it, even though it's sort of pointless.
 

MacMadame

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Based on the crud’s closest relatives of original crud and Middle Eastern crud, I and every other immunologist I know is going to be shocked if infections at and above a certain threshold so not confer protective immunity. But, we have to do the studies with the crud itself before setting policy and not just make policy off of assumptions.
What does "above a certain threshold" mean?
 

BlueRidge

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I actually unsubscribed from the Washington Post yesterday because I was so tired of this kind of thing (in relation to a different article). Given the psychological stress people are under already, it is just grossly irresponsible. It's not just them, but at least I felt like I was doing one small thing to protest against it, even though it's sort of pointless.

:confused:

I read about what the WHO said in the Post and came away with exactly what aka_gerbil said in her post.

I find the Post among the most reliable news sources. They all have problems, like every other human endeavor.

@acraven the Chinese vaccine was reported about in Science, here is the article, although it doesn't say anything different from what @Hedwig posted.
 

clairecloutier

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I just thought the short WHO piece in the Globe was worth posting because I've seen many suggestions, in various articles, that one way to re-open society would be to test people for antibodies to the crud and then let them return to work if they do have antibodies--on the assumption that they would not get it again.

So, if the WHO is saying that there's no proof yet that having antibodies prevents a second infection, that would mean that policies based on positive antibody tests are premature. (As @aka_gerbil is saying.)

I wasn't totally seeing it as alarmist news, but mostly as a piece of information with policy implications. (Although, it sure would be reassuring to know that getting the crud would in fact confer immunity. I'd feel a lot better if they could establish that.)
 

aka_gerbil

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What does "above a certain threshold" mean?

The short, possibly oversimplified, answer is "was the magnitude of immune response in the individual high enough to lead to protective immunity." Generally, there is a correlation between high neutralizing antibody titer and protective immunity down the road. It's a YMMV situation between different pathogens, the individual animal/person, and how long that protective immunity lasts.

There are several hypothesis on how immunologic memory develops, but the mechanisms are not yet fully understood and there are still a lot of questions. A person or animal is exposed to a pathogen it hasn't seen before. The first line of defense is innate or non-specific immunity. The goal here is to keep the infection under control until specific/adaptive/acquired immunity can kick in, usually after 4-7 days. I'll skip the nitty gritty details because I don't think anyone wants to here about antigen presentation, affinity maturation of B cells, etc. , but part of this is the generation of specific antibodies against the pathogen that can bind to it. It also includes T-cell responses. Somehow, there ends up being a fraction of B and T cells that become long(er) lasting memory cells that can hang around and be reactivated quickly if they see that same antigen again in the future.

Sometimes, the innate immune system can clear a pathogen on its own. If you end up with an adaptive immune response and antibody generation, level of neutralizing antibodies are going to be elevated in the short term after infection. You need to follow people over time and repeat the titer tests to see if immunity persists. I think with original crud, they found that immunity wanes (but doesn't dissappear) after about 6 years. (Which makes me personally think when we get a vaccine that works, we may need boosters every 5 years or so to maintain immunity.)

If you have someone who only had a mild infection by the crud and a weaker adaptive immune response, it might not have been enough of an immune response to end up with memory B and T cells that remember seeing the pathogen before.

Claire--I think that is exactly why WHO put out the statement. There's been a lot of focus on antibody testing as some panacea of being able to reopen society, but we don't have the data yet for this particular bug to say that someone having antibodies to this means they're immune forever and ever and ever. We have to study this particular bug to know if being sick with the illness confers immunity and if so, for how long. That said, if we look at its closest relatives, odds are high that provided someone had a robust enough of an immune response when they contracted it, then they're probably going to have immunity that persists for 5-6 years before waning (at which point, we'll presumably have a vaccine and these people would need to be vaccinated too to maintain their immunity).

The utility of antibody testing at this point is that this crud can run the gamut from asymptomatic to death and testing for antibodies is another measure we can use to determine prevalence in the population. Having that information is important in working out the true rates of infection, illness, and death.
 

MacMadame

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This is an interesting approach to PPE.


The article makes it seem like there is no downside to these respirators but I think I wouldn't want to be treated by someone wearing this. It would make me feel like I was in a dystopian movie. Or that robots were treating me.

ETA here's another idea: https://www.israel21c.org/in-******...-pilots-*****-neutralizing-sticker-for-masks/
 

MacMadame

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There more effective than N95 and they’re reusable. Win win.
Yes, they are what I thought Healthcare professionals had. I mean I know they use the disposable ones most of the time, but I figured they got something like this on graduation that they could use for crazy serious situations. Little did I know that nothing like this was happening.
 

KCC

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I still have one of those North masks from my time in a manufacturing plant. My plan was to use it as part of a Halloween costume, going as some kind of a bug. It probably doesn't fit me anymore, but maybe I can find which box it is stuffed in and pass it along to someone who can get a fit-test.
 

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