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Mudguard

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  1. Democrats have to make it clear to Mitch McConnell that they will pack the Supreme Court if he replaces Ginsburg with a Trump nominee. That's the only thing that might give him pause. Packing the Court would undo everything he's done to stack the Supreme Court with conservative Justices, and it would ruin his legacy. There needs to be outrage and agreement among the Democrat voters and politicians, that is reflected in the polls, to scare McConnell off. I think there's just too little time for them to nominate, vet, and confirm a justice in 45 days, so if McConnell wants to do it this term it will likely happen after the election. Trump will have to nominate someone next week or so for this to work. It's going to be a huge election issue for both parties. Would threats to pack the Court rally Republicans to show up to vote? Probably, but I have no idea how this issue will balance out right now.
  2. I think the FDA will have access, but I'm not sure whether everything they consider is made part of the public record. If the data is going to be released anyway, why not release it now? I suspect that any publicly accessible report may only have a limited amount of information, like the conclusion of the hold review, but not any of the supporting details. That's what we have for the first review hold, at least so far. The lack of transparency is problematic, especially with all the skepticm surrounding the politicization of the vaccine.
  3. AstraZeneca is resuming it's vaccine trial in the UK. But they aren't releasing any additional information about the two holds, citing patient confidentiality issues. Not sure how they can morally justify this when they thought it was ok for the CEO to brief some investors in a private call earlier in the week about the two holds. They are working with other countries to restart the trials.
  4. It's not over yet, but they need to release more details about the two cases. With the first case, how confident are they with the diagnosis of MS and that the vaccine was not responsible? If the person was suffering symptoms of MS before the start of the trial, OK. If the symptoms only started after receiving the vaccine, then I'm not sure how they can rule out the vaccine as the cause, when the ultimate cause of MS is generally unknown. The cat is out of the bag now, so they need to provide a lot more details, at least with respect to the first case, where the review is already complete, and then for the second case when the review is completed. Transverse myelitis occurs in about 1 in a million or less for the other vaccines that have been approved. It's extremely rare. If one or both cases are attributed to Oxford's vaccine, it would occur roughly 100 times more frequently. I was willing to write off one case as bad luck, but the existence of the other earlier case makes me much more doubtful. Let's see the data and analysis for the first case. I'm not willing to just take them at their word.
  5. Apparently, the CEO of Astrazeneca confirmed in a private conference call with investors on Wednesday morning that this was the second time the trials have been stopped after a patient had suffered neurological symptoms. The first case was attributed to multiple sclerosis, that they did not find to be caused by the vaccine. Second case has symptoms consistent with transverse myelitis, but as of Wednesday morning, the diagnosis was not officially confirmed. He also confirmed that the second patient received the vaccine, and not a placebo. Both diseases involve damage to the myelin sheath surrounding nerves from an autoimmune response. The symptoms and potential causes of the two disease have a large overlap, so I think they need to revisit the first case. I think it's over for this vaccine. I don't think they can just waive the second case off as another case of multiple sclerosis or some other similar disease that is caused by something other than the vaccine.
  6. I'm guessing that they are testing the patient to see if they can identify a potential autoimmune disorder or infection that could have caused the transverse myelitis. If not, I think they'll have to assume that the most likely cause is the vaccine. This is a really serious disease that often results in permanent symptoms, and an incidence of around 1/20,000 would be unacceptable. I think they end the trial if they determine that the vaccine is likely responsible. There are plenty of alternative vaccines in development, so there currently isn't a pressing need to go forward with any particular vaccine.
  7. Right, they aren't randomly selecting the compound. The vaccines are based on the virus itself or a critical component of the virus. The theory behind all the vaccines is sound, but in medicine, that frequently doesn't lead to efficacy. Biological systems are often extremely complex and still not well understood, which result in the frequent failure of vaccine and drug candidates. We really have no idea about the efficacy of a vaccine until in completes the phase 3 study. You can do some preliminary testing like seeing if the vaccine can generate a neutralizing antibody response using blood tests, but this doesn't always correlate to vaccine efficacy in the real world. All the leading candidates have generated neutralizing antibodies in blood tests performed in the lab, which only means that the vaccine is promising enough to go onto the next phase to determine real world efficacy. We still have no idea whether these vaccines actually work. The vaccine challenge studies are not as simple as you think, unless you are willing to deliberately infect a control group that has not been vaccinated. Without a control group, you can't really say anything about the efficacy. You run into the same problems as all the early therapeutic coronavirus drug studies that were conducted without a control. I've listed some of the problems in a previous post. Other problems include destroying public confidence in the vaccines if the first couple of candidates are failures. How long can you continue to get people to volunteer to get infected by a potentially deadly disease if the first 5 or 10 vaccine trials result in failure? I don't think it will be that easy to get people to volunteer to be infected for even the first trial. Regardless, this isn't an option in the US, Europe, or anywhere else in the free world right now, so people need to do what they can to reduce the likelihood of infection until we find an effective vaccine. The other approach would be to go the route of China or Russia and just distribute the vaccine widely and conduct the phase 3 study simultaneously, and cross your fingers that it actually isn't harmful and provides some degree of protection. I'm not a fan of this approach, especially when effective means of controlling the pandemic already exist, but just aren't being implemented.
  8. Adenovirus based vaccines have been in R&D for decades, but have yet to result in a commercial vaccine. Impmk2 has described it correctly. You are using a genetically modified adenovirus that has been modified to include a gene that encodes the spike protein and whatever other antigens you'd like to use. You are not delivering the antigen itself directly. Oxford is using a chimpanzee adenovirus to try and get around antibodies against common human adenoviruses that are present in many people. I have no idea how much testing in people the chimpanzee adenovirus has undergone. ETA: Technically, the Russian vaccine is also an adenovirus based vaccine (using a human adenovirus), so there is now one product sort of on the market, albeit with limited testing.
  9. Because the vaccine has probably been given to less than 30,000 subjects, the current risk is going to be at least 1 in around 20,000 to 30,000 (however many have been dosed so far), at least for now. For a vaccine that is going to be given to hundreds of millions of people, that might be too much. Hope it's not caused by the vaccine. Eta:. Trials are only paused for serious adverse events, like things that require hospitalization or end in death.
  10. No way to know until they release more information. If the vaccine is responsible, it really depends on the nature of the adverse event, why it happened, and how likely it could happen again. But yes, an adverse reaction caused by the vaccine wouldn't necessarily doom the vaccine. For example, maybe it was a dosing error, or contamination issue, both of which could be fixed.
  11. Wow, hopefully it turns out the adverse event was not caused by the vaccine, and they can resume the clinical trials soon. Also hope they release more information soon. It's possible though that they'll wait until they figure out whether the vaccine was responsible. If none of the first three vaccines pans out, we could be waiting a while for a vaccine. I'm not sure how far along the traditional inactivated or live attenuated virus vaccines are. Inactivated virus vaccine candidates are probably much further along than live attenuated virus vaccines though. China has published results from a phase 1/2 trial of an inactivated virus vaccine, so they are certainly well underway.
  12. There is something similar going on in Sweden too, where the case numbers, and particularly the number of deaths, rapidly plummeted around the end of June, despite little change to official health guidelines. The Swedish health authorities have also speculated that herd immunity may be playing a role, but the numbers of infected determined by antibody testing studies isn't anywhere near the required levels to achieve herd immunity. Better infection control management at nursing homes has also played an important role in keeping the numbers of deaths low. People have speculated that perhaps there is some level of cell-based immunity that is not being detected by antibody testing, but this needs a lot more work before it is proven. Perhaps a portion of the population already has some level of immunity based on previous infection with a related coronavirus strain. If this is the case, it's another reason why a control group is needed for the vaccine studies. Otherwise, the efficacy of the vaccine will be overstated. Perhaps the people that are most at risk are taking more care, but the rest of the general population still remains relatively lax. It's something to monitor, especially as winter approaches. If the hardest hit areas such as Manaus, Stockholm, NYC, northern Italy, etc., all avoid a second wave this winter or as measures are relaxed, there may be something to this. Even if this turns out to be the case, most places in the world have not been hit nearly that hard, so we cannot assume that many other places are at or close to herd immunity levels.
  13. I don't know what you mean by "type of vaccine." If you mean whether the vaccine is a live attenuated vaccine (i.e., measles vaccine, nasal spray influenza vaccine) or an inactivated virus based influenza vaccine, then none of the three vaccines under consideration in the US (Moderna, Pfizer, Oxford) or the Russian or Chinese vaccines are based on either of these technologies. Even if they were based on one of these technologies, you cannot assume that the performance of an live attenuated vaccine is always as good as the measles vaccine. For example, FluMist sometimes performs worse than the traditional inactivated influenza vaccine, which already is a mediocre performing vaccine at best. All the early vaccine candidates are based on unproven technologies that have yet to result in a commercially sold vaccine. Consequently, there is even more uncertainty around these vaccines than usual. We have no idea how well any of these vaccines will work. It could range anywhere from actually increasing your chance of getting infected to 80+% effective. Your comment that they should just come up with a better vaccine rather than do the testing if the effectiveness is around 50% or less is nonsensical. Again, the effectiveness of the vaccine is unknown until it's tested in clinical trials. I don't get why you think this is something that is known beforehand. Normally your posts are logical, even if they may be controversial, but there appears to be a big disconnect here. There are over 150 vaccine candidates under development, and we have no idea about the efficacy of any of them. I read the challenge guidance paper, and the WHO is not saying outright that coronavirus challenge studies are OK. They are merely recommending that anyone considering doing a challenge study needs to consider 8 criteria before making a decision whether to proceed. Also, since the WHO doesn't really have any actual authority over any country, they cannot allow or prevent countries from going forward with challenge studies, at least to the best of my knowledge. Anyway, criteria 2 is about assessing the risks and benefits of conducting a challenge study and trying to weigh the two against each other. Currently, I don't think potential benefit of possibly speeding up the approval time exceeds all the risks of deliberately infecting subjects with a potentially deadly disease, for many reasons. For example, the WHO paper recommends only recruiting young healthy subjects that are at low risk for suffering serious symptoms. However, young healthy subjects are the group that needs the vaccine the least. We really want to know how well the vaccine protects the most at risk people, like the elderly and people with underlying conditions. It is risky to assume that if the vaccine performs well in the young and healthy, it will also perform well in the elderly and/or sick. It's also not clear to me how much faster the challenge study would be. Potentially, it could be quite a bit faster, say around at least 4 months faster if the standard trial takes 6 months to complete, but there are many unknowns around this. It's not clear to me how many subjects would be needed, and how quickly they'll be able to recruit willing subjects. Will they require a certain number of minorities to be recruited? The US already has a shameful history of medical experimentation on Black people so there is a higher level of distrust regarding medical testing, which is already making recruitment difficult in the current vaccine studies. I think it'll be even harder to recruit black people for a challenge study, at least in the US. Also, how long will it take to figure out the right dosing? And how easy will it be to find willing guinea pigs for the dosing studies? Will the artificial dosing result in an laboratory determined efficacy that matches real world efficacy? To improve recruitment, especially when there is a significant risk involved, money is often handled out as compensation. Also, it's probably difficult for many people that work to just take off a month or so to participate in a clinical study. I think it's very likely that a disproportionate number of subjects will be recruited from the poor. Ethically and morally, this is problematic as well. I think it's telling that the US has not seriously considered doing a challenge study. No one wants a vaccine sooner than Trump, and it's clear he is doing everything possible to speed up the timeline. I assume that his administration considered it, but ruled it out. I can't imagine that a challenge study will be conducted in the US. A challenge study should only be a last resort type thing to do here, and when we won't even mandate enforceable mask usage across the country and/or uniform social distancing measures, it's impossible to justify the necessity of a challenge study. We're going to deliberately infect the poorest and most desperate of our country so that a bunch of morons can continue to refuse to wear masks or socially distance? We haven't fallen quite that low ... yet.
  14. It sounds like you are suggesting that they should be deliberately infecting clinical trial subjects with SARS-CoV-2, when we don't have any really effective treatments yet. That's crazy, and was never seriously considered anywhere in the world, as far as I can tell. Such a clinical trial where subjects are challenged with a potentially deadly virus with no cure would violate numerous ethical rules and guidelines, and I can't imagine such a trial actually getting approved. Old people and other types of susceptible people would need to be tested too to see if the vaccine protects these types of people. You are OK with deliberately infecting all these people? Maybe the vaccine doesn't work. A large portion are also getting a placebo. Bunch of people would die during such a trial. I don't have a problem with how the clinical trials have been set up. They are being completed at record speeds, as it is. They've compressed down the timeline from years, to months.
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