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Covid-19

Vaccine Transparency

I’ve been emphasizing for some time that our efforts to find and deploy a coronavirus vaccine have to be as transparent as possible to increase the chances for success. Recent events make that more clear than ever – and not in a good way.

Update: Moderna has now published their complete clinical trial protocol, and good for them. Where are the others? I should note that I’ve seen talk on Twitter that there was a Freedom of Information Act request pending for this, and that could be a reason it was disclosed (I can’t verify that yet, and I don’t know to what extent an FOIA request would be able to do this, although since there is federal funding involved, perhaps it could). But either way, Moderna is now the most transparent of the vaccine efforts, a position they did not hold before.

Second update: and now they’ve been joined by Pfizer and BioNTech, whose clinical trial protocol can be found here. Very welcome news!

The Oxford/AstraZeneca trial has restarted in the UK after the adverse event that was recently reported. But what do we know about it? Not much, as this New York Times piece by Katie Thomas details. The only time that the company’s CEO (Pascal Soirot) has spoken publicly about this came during a private J. P. Morganled conference call with investors, and the remarks had to be leaked (and published by Stat, for which thanks) for the rest of us groundlings to hear about them at all. His remarks confirmed the Times’ earlier reporting of symptoms consistent with transverse myelitis, but AstraZeneca has not allowed those words to cross their lips in any official statements, from what I can see.

That’s flat-out unacceptable. Ed Silverman’s editorial here is correct: the company missed a serious opportunity to show that it’s conducting this research where everyone can see what’s going on, and (even worse) has raised more suspicions that they’re not forthcoming with details. The fact that the most detail anyone’s heard about this situation came in a private investor call makes things even worse, of course, if you’re trying to demonstrate that it’s not actually all about the money.

We already have enough problems with those suspicions as is. The Morning Consult polling group has been registering a constant decline in the number of people who say that they would take any coronavirus vaccine at all, and is behavior like this going to bring those numbers back up? We’re going to need a substantial part of the population vaccinated, from what I can see, but that’s obviously not going to happen if enough people think that they’re taking something that’s unsafe or ineffective. Those opinions cannot be swayed by saying “Trust us, we have it under control” while you chat with institutional investors and J. P. Morgan about the real story.

There are even larger issues. As Thomas’ article notes, none of the leading vaccine efforts have made their detailed clinical trial protocols available. To pick two examples, we don’t know when their Data Safety Monitoring Boards meet for review, and we don’t know the criteria for stopping any given trial for efficacy.

It’s standard for drug companies to withhold details of clinical trials until after they are completed, tenaciously guarding their intellectual property and competitive edge. But these are extraordinary times, and now there is a growing outcry among independent scientists and public health experts who are pushing the companies to be far more open with the public. . .These experts say American taxpayers are entitled to know more since the federal government has committed billions of dollars to vaccine research and to buying the vaccines once they’re approved. 

I suppose as drug discovery researcher I am a small member of that community of experts, so let me add my voice. We are indeed entitled to know more. I realize that Pfizer and BioNTech have deliberately chosen to fund all their own work without any help from the “Warp Speed” initiative, but plenty of others have taken such funding. And even in Pfizer’s case, the government is going to be one of the largest customers for any vaccine that emerges from their work, and it is obviously in the public interest that people have confidence in such a vaccine and in its development process and regulatory approval.

I well realize that this confidence is being eroded from several directions at once. Between (1) the more traditional anti-vaccine people, and (2) the ones who think that the entire coronavirus epidemic is some kind of evil fakery that will culminate in an evil fake vaccine forced on the public for evil purposes, and (3) the people who are OK with vaccines in general but feel that these new ones may well be too rushed, and (4) the people who feel that the administration itself may be doing some of the rushing in order to get something out before the election, safety be mostly damned, the middle ground is shrinking.

We just had a statement (an unprecedented one) from a whole group of drug companies working in this area, with an “on-going commitment to developing and testing potential vaccines for COVID-19 in accordance with high ethical standards and sound scientific principles“. We’d damned well better, is my first reaction, but sure, this is a good thing to emphasize. But nowhere in that statement is there anything about putting cards on the table. It’s time. The companies developing vaccines for this pandemic have to break with past behavior and “normal” drug development and be more public about these trials than they have ever been. These are unprecedented times and we need to see some more unprecedented behavior. Fast.

208 comments on “Vaccine Transparency”

  1. Sc says:

    I don’t want to be pessimistic but I bet that the transverse myelitis will not be an isolated incident, and I also wonder if the earlier MS case in the trial was actually unrelated. They needed to get ahead of this and have probably missed their shot.

    I have been seeing more of my friends and acquaintances going whole hog (perhaps even hog wild) on suspicion of any vaccine. It’s very unfortunate (though I understand why peoples’ trust in institutions has eroded)–it will definitely take some work to change their minds.

    I just got my first injection in the pfizer trial (I think I barely slipped in because they expanded the number of people). The PI seemed extremely darned upbeat about things which was encouraging. My arm is pretty sore so I’m hopeful I got the real deal.

    1. Hopeful Layman says:

      That Pfizer is expanding their sample population can only be a source of optmism — we need as much diversity as possible in these trials. If anything might make a dent in “vaccine hesitancy,” it will be this kind of thing. It’s a little confusing, though, that even as Pfizer is including more people in its trials (which, presumably, should make them take longer), at the same time Albert Bourla is predicting results by October, and rollout before the ene of the year. Isn’t this contradictory?

      1. paperclip says:

        They still think that the original 30,000 participants are enough for “the answer,” but the additional participants will a little more closely match the broader population, because teenagers who are at least 16 years old can be enrolled, as well as people with HIV and hepatitis B/C. Having more participants will overall sharpen what we know about safety and efficacy.

        I don’t think we will have results in October, though. I don’t believe they will have captured enough events of COVID. (I’m also participating in the trial, having recently received the second shot, and I’m semi-sure I got a nice dose of saline each time.)

        1. Dark Day says:

          Paperclip, I agree 100%, And let’s not forget Novavax, who came into the game a little later than the others, and whose Phase III trials are projected to begin to yield results by December, but probably later. I don’t know how they’re selecting their sample, but I certainly hope they follow Pfizer’s good (and still growing) example.

        2. Anonymous Coward says:

          Well, being semi-sure is a safe bet, since half of all people get water with salt 🙂

          1. x says:

            If the placebo is really just saline, then a strong inflammatory reaction should indeed be casual evidence that you got the real thing.

      2. Chris Phillips says:

        On a timeline produced by an analytics company called Airfinity, the estimate was that Pfizer would produce interim results by mid-October.

        I assume the thinking is that if the interim results for efficacy were sufficiently clear-cut, they could proceed on that basis, while the additional participants they are now enrolling would enhance the safety data – at least as far as possible side-effects soon after vaccination are concerned.

        1. debinski says:

          In their original protocol (stage/phase 1 data published in Nature) that includes phases 1, 2 and 3, they calculated that they only needed 53 cases of COVID-19 to prove efficacy with an assumption of a 70% true vaccine efficacy. They also assumed 1.7% incidence of COVID in the placebo group and 20% of subjects would be unevaluable. Based on these numbers they calculated they needed only 3000 participants/group. But apparently they never ran stage 3 of the protocol and started a new phase 2/3 protocol (or revised the original) that is now running in the US and elsewhere. But the protocols are very similar based on what I know about the current protocol because I’m in the study. I’m guessing they upped the N to 30,000 by lowering their VE to 50% and shortening their timeline for results. Based on these numbers it does seem having efficacy results in October is likely. Here is the original protocol. See page 95 for power calculations:
          https://static-content.springer.com/esm/art%3A10.1038%2Fs41586-020-2639-4/MediaObjects/41586_2020_2639_MOESM1_ESM.pdf

          1. Chris Phillips says:

            Reuters reports on documents describing the criteria for Pfizer’s analysis of its interim results. Apparently the first stage is based on just 32 infections developing, and demonstrating efficacy on a sample of this size would require the vaccine to be 76.9% effective.
            https://www.reuters.com/article/health-coronavirus-usa-vaccines/focus-pfizer-vaccine-trial-bets-on-early-win-against-coronavirus-documents-show-idUSL1N2GC1U0

            That appears to imply the trial is 50-50 vaccine and placebo, and they need 6 or fewer of the 32 infections to be in people who received the vaccine.

            Given the size and duration of the trial, it seems surprising that they haven’t reached 32 infections yet. But I suppose people who volunteer for vaccine trials will not be representative in their behaviour. I wonder what those clever analysts assumed about that when they put together their timeline.

        2. Chris Phillips says:

          Regarding the accuracy of Airfinity’s estimates – their estimate for interim results from Moderna was mid to late October. According to the UK Financial Times, Moderna is now saying October is possible but unlikely; November is most likely; and December is the worst-case scenario, in which the infection rate in the USA slows.

          1. Chris Phillips says:

            Here is the protocol which has been released by Pfizer:
            https://pfe-pfizercom-d8-prod.s3.amazonaws.com/2020-09/C4591001_Clinical_Protocol.pdf

            The “success criteria” for the interim and final analyses are:
            6 or fewer vaccinated participants out of the first 32 infections
            15 or fewer out of the first 62
            25 or fewer out of the first 92
            35 or fewer out of the first 120
            53 or fewer out of the first 164 (final analysis)

          2. Chris Phillips says:

            AstraZeneca has followed Pfizer and Moderna in releasing its protocol:
            https://s3.amazonaws.com/ctr-med-7111/D8110C00001/52bec400-80f6-4c1b-8791-0483923d0867/c8070a4e-6a9d-46f9-8c32-cece903592b9/D8110C00001_CSP-v2.pdf

            In this case there is only a single interim analysis, when approximately [?] 75 infections have been observed, that is half of the number required for the primary analysis.

          3. Chris Phillips says:

            No doubt someone will correct me if I am wrong, but apparently in all three trials the success criteria are based on ruling out a hypothesis that the true vaccine efficacy is 30% (or less), and the power calculations are based on an expectation that it will be 60% (or more).

          4. Marko says:

            Per Eric Topol , the efficacy target for AstraZeneca is 50% , not 60% like the other two. A summary chart :

            https://pbs.twimg.com/media/EiTfDvyUwAAPog4?format=jpg&name=small

          5. Chris Phillips says:

            I think Eric Topol has misunderstood. They all seem to be using the 60% efficacy hypothesis in the same way – to do their power estimates. And they are all using the same success criterion, which is ruling out a 30% efficacy hypothesis. But AstraZeneca are stating an additional condition – that the observed efficacy should be at least 50% too. (In a large enough trial, of course you could rule out the efficacy being as low as 30%, while observing an efficacy of less than 50%. But apparently not quite in trials of this size – Pfizer say that the 30% criterion would imply an observed efficacy of at least 52.3% at the final stage.)

          6. Marko says:

            Yes , I think you’re probably right , based on the Pfizer final analysis target numbers. Topol reviews a great quantity of new material on twitter , but not always with such great quality.

    2. anon says:

      What would be the best way to show that the transverse myelitis and vaccination were related?

      1. Not-an-epidemiologist says:

        Given that ~60% of TM cases are idiopathic it’s going to be hard to prove or disprove association with the vaccine here, I’d imagine. However, a clear link with one of the known causal factor would at least help reduce the chance it’s related to the vaccine (and I assume that one was found, given how quickly the trial was resumed). On the other hand, should a second incidence of TM occur within the trial, that would be highly improbable.

        At 4.6 new cases of TM diagnosed per million per year, the probability of one case appearing by chance alone within the 15K vaccine group *this year* is ~6.7%. The trial hasn’t been running for a year, so presumably the probability is lower for the 2-3 month time period of the trial, the exact amount depending on seasonality of the disease, but likely around 2%. (This estimate may also be confounded by the age of trial participants — TM does not affect all ages equally.)

        So finding one case in your vaccine group is pretty unlikely, but not impossible. Two cases, though … that would definitely be cause for concern.

        1. Daren Austin says:

          15,000 x 4.6/1,000,000 (cases/yr) is an expected 0.069 cases per year. Suppose you have a median of three months of observations from participants (0.25 yr), that means an expectation of 0.017 cases out of 15,000. It’s a rare event under the null hypothesis – about 1 in 870k people dosed. A second or even third similar AE of this type would be very concerning.

        2. confused says:

          That might be the chance of TM occurring by accident, but I think the chance of *some* rare potentially-vaccination-related disease occurring by accident would be a lot higher.

          Two cases of the *same* thing would change the statistical picture a lot more, wouldn’t it?

        3. Riah says:

          I wonder if some or maybe lots of the so called “idiopathic” cases were also vaccine related – if the time between vaccination and symptoms is greater than a few weeks, the connection wouldnt have neccessarily been made.According to the index of the inch and a half thick collection of 70+ papers in Vaccines & Autoimmunity (Wiley Blackwell), there are references to it under many vaccines.I haven’t got time to wade through all those papers right now but maybe someone will….

    3. Riah says:

      I agree, they should reveal their reasoning for concluding the July case was unrelated to the vaccine. Simply stating that was the conclusion of their investigation instils no-one with confidence! The mother of the girl recently suspected of having TS revealed a few days ago on social media (inadvertently probably) that she had been in hospital (named) ever since. Her other daughter showed no ill effects.

      The following was reported in the UK Telegraph, even acknowledging these conditions can be caused by vaccines which surprised me as the actual print copy did not include that part:
      https://www.telegraph.co.uk/global-health/science-and-disease/oxford-vaccine-trial-suspended-not-doomed-uk-woman-hit-rare/

    4. Steve Scott says:

      Update Sep. 17. Moderna releases huge amount of info. on Phase III tests
      https://www.nytimes.com/2020/09/17/world/covid-19-coronavirus.html

      1. Hopeful Layman says:

        Mind a “Layman’s” question?

        RE: “A total of 151 cases — spread between the vaccine and placebo groups — will be enough to determine whether the vaccine is 60 percent effective. The Food and Drug Administration has set the bar at 50 percent.”

        Does this mean that as soon as 151 cases are available, and assuming that the vaccine is then shown to be at least 60 percent effective, we won’t really know whether it’s actually more effective than that until after it gets rolled out and a sufficient number of people have actually been vaccinated? In other words, will we not know the “true” efficacy of a vaccine over and above that baseline (meaning that we won’t really know how much uptake will be essential) , until we’ve actually seen the vaccine at work in the “real world”?

        Sorry if these are stupid quetions, but with all the projections we’ve seen on the relationship between efficacy and uptake, in terms of helping to bring about mass immunity, I am very curious about this.

        1. The 151 cases number comes out of what statisticians call a power calculation.

          Suppose that 10 cases are seen in a trial. If 6 were in the placebo population (A) and 4 in the matched, actively-treated population (B), then you might guess that the treatment is 33% effective. But that guess would be insecure: if the treatment were 0% effective, a 6-4 split would arise about 21% of the time just by the play of chance. With the same ineffective treatment, one might see a 7-3 split about 12% of the time, and even more extreme imbalances now and then.

          Even a 10-0 split could arise with a lucky but ineffective therapy, but this occurrence is so unlikely (<1%) that such a result would be convincing evidence that the treatment was better than nothing. It would _suggest_ that the treatment might be 100% effective, but this estimate would be shaky. For example, a 50%-effective treatment would get a 10-0 split about 2% of the time.

          The more cases there are, the easier it is to be confident ("confident" is not as good as "sure") that your results are not the play of chance. The statisticians here assumed that the treatment efficacy might be around 60%. With 151 events, the expected split would then be something like 108-43, but of course chance could let it be anything from 151-0 to 0-151. The choice of 151 let them determine that — again, assuming that 60% is the treatment's true efficacy — the chance that they would get a result that was plausibly nothing but good luck for an effective therapy was acceptably low. That is, only at the unlikely edge of the range 107-44, 106-45, 105-46, … does one enter territory that might plausibly be just the result of good luck.

          The power calculation is done at the trial-design stage. Once they actually have the results, there are different considerations. If the observed split is 151-0, then this is a result that might occur with an ineffective therapy, but the probability of that being true is less than 1 in 10^45. If the observed split is 111-40, then they will have their desired result, and their best (but insecure) estimate of the treatment's efficacy will be 64%

          1. Typo: In the 3rd paragraph, “<1%" should be "<0.1%"

          2. Typo #2: “good luck for an effective” should be “good luck for an ineffective”

  2. Dark Day says:

    To Derek’s “several directions at once” taxonomy, I’d add African-Americans and other people of color who have legitimate historical reasons for distrusting the American medical establishment, especially as it intersects with the government.

    Meanwhile, although I realize that a lot of people here will think that these numbers are unduly pessimistic, projections still indicate that even a relatively modest amount of “vaccine skepticism” in the U.S. could serioulsy hamper, if not derail, any vaccination-driven attempts to establish significant immunity here:

    https://www.newsweek.com/coronavirus-vaccine-stop-pandemic-1527697

    1. WST says:

      IMHO the study is too pessimistic, they use a derivate of SIR type model, that has assumptions never met in reality and predicted things like “herd immunity” that never materialised during epidemics.
      The modelling did not account for early vaccination and removal of the vulnerable and healthcare professionals, two viral ecosystems responsible for lots of infections. If these two groups can be removed from the equation, covid will change nature (mortality rates between <40 and 65+with co-morbidities is two or three orders of magnitude).
      IMHO effects of vaccinations will be highly "non-linear", with huge early benefits.
      France has a big second wave of infections, if there were no vulnerable subjects, there would not be any surge in hospitalisations.

      1. Dark Day says:

        Yes, and the model also doesn’t take into consideration the distinct possibiilty that many more people in the U.S. already have at least some partial immunity than we know about. I’m sure most asymptomatic carriers have never been tested, and I think the question remains whether even some people with very mild symptoms may have some immunity based on prevsious exposure to related coronaviruses. If this is the case, “herd immunity” (or at least significant mass immunity) could occur much more readily than a model like this might predict. But that may be optimism on my part, which unfortunately seems to have very little to do with realism.

      2. Dark Day says:

        “. . . IMHO effects of vaccinations will be highly “non-linear”, with huge early benefits.”

        This may be true for deaths, but most likely not for cases. For quite some time, now, new cases have been increasing primarily among younger people, even though most of the deaths and hospitalizations continue to be seen among those over 65. At least as things stand now, new cases are reported (and understood in most people’s minds) with the same sense of urgency and dread associated with actual deaths. So until/unless the vaccine gets distributed among the general population AND uptake among that population is extremely robust, new cases will continue ton occur at a rapid rate, and the overall sense of dread and helplessness that cripples so much of our everyday conversation about COVID, and which has taken such a toll on our economic, social, and mental health, will remain dire.

        1. Chris Phoenix says:

          Death isn’t the only long-term negative outcome. People – even young people – are getting heart, lung, kidney, and neurological damage. I’m probably not likely to die from it, but I’m sure going to try to avoid getting it!

        2. confused says:

          “the overall sense of dread and helplessness” I think is mostly because this is new. Fear of the unknown.

          That factor will go away with simple time… and with our current media-driven, fast-moving society, probably not all that *much* time. If COVID doesn’t have a major fall wave in the US most of the fear will likely be gone by Valentine’s Day… earlier in many communities.

          Fear of COVID among young people seems to me to be primarily “fear of the unknown”. Certainly that’s true of me… I’m 30, and the main reason I’m personally concerned about it is fear of unknown potential long-term effects (even though the few bits of data I’ve seen on that don’t strike me as very convincing).

          Of course I don’t *want* to get it — I wouldn’t want to get the flu either — but the risk of hospitalization (under 1%) and death (well below 0.1%, probably a lot below) in my age group in and of itself wouldn’t warrant changing my life drastically to avoid. Certainly given that I never worried about things like malaria when traveling in areas where it’s common … because those things have well-understood treatments.

          1. Dark Day says:

            I wouldn’t count on COVID not have a “major wave” this fall — it’s starting to spike in states that previously did not have extremely high numbers. I also think it will continue to tear through college campuses, and eventually the college towns where those campuses are located. And again, remember that virtually all of the public policies we have in place — restrictions on businesses, interstate travel bans, masking/”distancing” requirements, etc. — are based on CASE rates, not just fataltiy rates. The assumption is that “low-risk” people who contract the disease will spread it to higher-risk people (hence Fauci’s admonition that college students who contract the virus should not be sent home). Even after a vaccine is introduced, those higher-risk people will still be at *some* risk (no vaccine is 100% effective). So, unless we decide to buid “COVID isolation camps” to quarantine senior citizens and anyone with pre-existing conditions, I don’t see any of this changing.

          2. confused says:

            >>I wouldn’t count on COVID not have a “major wave” this fall

            It was an “if” statement. If one does occur, yes, public fear will be re-ignited. I’m not counting on anything particularly…

            But I don’t *expect* a major fall wave.

            >> it’s starting to spike in states that previously did not have extremely high numbers.

            Absolutely… but those states (largely the northern Great Plains) represent a small proportion of the US population, so it won’t show up as a major wave in the “top-line” national numbers. People in the rest of the US are not terribly aware of what happens there.

            (The Dakotas + Iowa + Nebraska combined have a smaller population than the greater Houston metro area.)

            All the very large states (CA, TX, FL, NY) and most of the mid-sized ones (places like AZ, GA, NJ) have been fairly hard hit already, though NY and NJ are in a class of their own (I think that’s mostly due to higher IFR due to worse treatment/understanding of the disease earlier, though).

            >>I also think it will continue to tear through college campuses, and eventually the college towns where those campuses are located.

            True – but college towns are young-skewed populations, so won’t translate to many deaths.

            >>And again, remember that virtually all of the public policies we have in place — restrictions on businesses, interstate travel bans, masking/”distancing” requirements, etc. — are based on CASE rates, not just fataltiy rates.

            Sure… but if fatality rates fall below “epidemic levels” and stay that way for a few months, cases will look a lot less scary.

          3. jbosch says:

            In the US it’s more of a continous wave with peaks, our third peak is coming. Just thinking about the universities reopening and bringing back their students. How come that all of the sudden so many campi are reporting a sudden increase in cases? Sure college kids might not get severly sick, but longterm effects just recently published in Nature suggest that one should at least consider that there’s more to it than death.
            And for that reason we developed a different dashboard that reflects COVID data and allows people to see more trends. I linked it in my handle. We also welcome feedback on our google form or you can dive into our medRxiv linked paper and leave comments there.

          4. Dark Day says:

            jbosch — Thank you for that! Very helplful and informative.

          5. confused says:

            I am pretty skeptical of a third peak… at least a third peak comparable in deaths. (The 2nd peak was about half as high in death terms as the 1st; halving that again would be below current levels.) Though of course it’s possible – no one can predict the future. COVID doesn’t seem terribly seasonal, though.

            There are states that are seeing their first major surge of infections (states with low % so far infected), so that could be argued to be a “third peak”, in the sense that the first was the Northeast + places like Detroit and New Orleans, the second was the Sunbelt, and now the third is the Northern Great Plains/western Midwest. But that set of states has a lot fewer people so it won’t look like a “peak” in the national numbers.

            Sure long-term effects are possible (I am skeptical that there will be a significant rate of serious ones in young people – the little actual data I’ve seen so far doesn’t seem that dramatic – but could be convinced by good data). Nonetheless, deaths continuing to drop will have a significant impact on public perceptions, and infections skewing toward college-age would mean lower deaths.

          6. jbosch says:

            You have to differentiate a bit here. So the first peak of infections which was followed by a death peak was different because a different population was mostly exposed. Now the second peak of cases had a massive shift towards younger folks getting infected but not sick enough to end up in the ICU, that’s why the death peak did not reflect a much higher rate compared to the case peak of 77K on July 16th. If you look at the data in a different way of who gets hospitalized and how many die, the trend has been the same ranging between 50% -43% not surviving when they get admitted to the ICU. I think we got a bit better at protecting at risk population more than we did at the beginning of the outbreak.

          7. Dark Day says:

            Yes — I fear that this supposed trend, both in the U.S. and overseas, of “increasing cases but leveling [or decreasing] deaths” is largely due to the fact that the most vulnerable people are now protecting themselves, both via PPE/distancing and simply by staying home and isolating themselves away from people. But they’re still vulnerable, and when their kids come home from college or gather around the Thanksgiving table with them, they’ll get just as seriously ill, and they’ll die at rates almost as high, as their predecessors did during the earlier months of the pandemic.

            Either way, predictions remain that deaths will reach approximately 400,000 in the U.S. alone before the end of the year.

          8. confused says:

            I don’t think so. Certainly there is an age effect – but treatments (both dexamethasone and maybe remdesivir, and better understanding of how to use things like ventilation, proning patients, etc.) should also have improved IFR, shouldn’t they?

            I’ve seen reports that deaths/hospitalizations ratio (hospitalization fatality rate) dropped sharply in the UK, though age effects could play a role there too.

            And yeah the IHME model predicts over 400,000 deaths in the US by the end of the year… but that model is absurd. The curve of deaths by time they show makes no sense. It shows the daily deaths rising *now* when they are in fact falling (and we should see a rise in hospitalizations before a rise in deaths, so that shouldn’t change in the next week or two).

            Even if COVID did exhibit flu-like seasonality, given time lag from infection to death, they have the deaths rising much too early.

            I would say the reasonable range is more like 250k (no fall wave) to 300k-320k (some fall wave). 415k is just ridiculous.

    2. Marjorie says:

      It is strange that Fauci considers an efficiency of 50% acceptable. Do they intend to combine 3 of them?

      1. Datawatcher says:

        I think it’s the FDA that said they’d settle for 50% — Fauci says he hopes for at least 70 – 75%, but he’s pretty much a team player (for better or for worse), so he’s willing to accept the 60% minumum baseline.

        1. DataWatcher says:

          Damn clumsy fingers! I meant, “. . . he’s willing to accept the 50% minumum baseline.”

      2. Anonymous Coward says:

        Not acceptable. Just better than nothing at all.

        1. jbosch says:

          Well, considering the efficacy of the RTS,S Malaria vaccine, 50% is much better already – and nobody complained about the ~30-35% efficacy and protection for about 6-12 months for the Malaria vaccine.

          1. Dark Day says:

            Is it possible (he asked cynically) that it might have had something to do with the fact that the malaria vaccine was targeted primarily toward Africam countries, and most of the putative “nobody” who had any complaints about it were located in relatively cushy/majority white European countries and the U.S.?

      3. Dark Day says:

        I admire Dr. Fauci, and I trust him very much, but I must say that his projections– regardless of whether he’s suggesting an “early” timeline or a more likely one, which would see approval occuring around the end of this year or the beginning of next year, with Phase I of the rollout to follow — seem to assume a level of efficiency in vaccine delivery and adminstration that seems extremely optimistic, even if we can assume that uptake somehow exceeds the level that most polls and interviews so far have predicted.

        https://wtop.com/coronavirus/2020/09/fauci-on-trump-cdc-vaccine-dispute-they-were-both-right/

        This hundreds-of-millions-of-doses rollout is unprecedented in its scope and complexity.
        Remember President Carter’s ill-fated 1980 hostage rescue mission in Iran ? Everything went as planned — until it didn’t. Maybe the old admonition that “there’s only one way for anything to go right is for nothng to go wrong” needs to be considered here.

  3. Matthew says:

    Where are the Congressional Committees?
    Surely they have a role.

    1. Fraud Guy says:

      The term coined by Steve Bannon is “flooding the zone with sh!t”.

      There is so much wrong going on through this maladministration that the House (as the Senate leadership cares little about what is happening) would have to spend 24/7/365 holding hearings (that administration members would boycott and/or misrepresent) to only fall behind that effort, let alone all the other oversight they would need to do.

      1. Matthew says:

        There’s some misconception that congressional hearings can only subpoena Executive branch members.
        They can call the executives and board members of companies, members of universities, researchers, etc.
        Waving this off and giving Congress a pass is disingenuous.

      2. Ol' Bone Spurs says:

        affirmative

  4. M says:

    I’m less concerned about the people in groups 1 and 2. Yes, they are loud, and it’s easy for me to ignore them, but not everyone does. But they are small in numbers.

    The groups in 3 & 4 are (probably) not “anti-vaxxers” and have legitimate concerns about the safety, efficacy and political underpinnings that are influencing vaccine development. And they are many in number. Exactly correct, Derek, that behavior like this doesn’t instill confidence in people who have legitimate questions about the process.

    Transparency is of utmost importance. But then, isn’t this usually the case? We can do better.

  5. Me says:

    I also just slipped into the pfizer trial. No reaction yet. The lady at the door said she had a fever that even. I will see. The lead doctor was Very upbeat. “When it is approved… good antibodies seen..etc.” my sister was in moderna trial and also had a 3 degree fever that even and a headache.

    1. David E. Young, MD says:

      I am in the Moderna trial. Had my first shot 3 and 1/2 weeks ago and my booster in two days. I had no reactions. None. Nada. Zilch. Of course, I could have received the saline placebo………

      1. PV=nRT says:

        Why the heck would they not use scrambled mRNA as a placebo?

        1. Mantis Toboggan says:

          Scrambled RNA id definitely a clear choice for in vitro experiments or even animal studies, but how would you design a scrambled mRNA that maximizes safety? Empty lipid nanoparticles seems like a good placebo to me.

          1. Riah says:

            Apparently a high proportion of people in the US have PEG antibodies and some might even be allergic – potential for anaphylaxis. So is that really a great idea? I don’t know much about this area so correct me if this is wrong anyone….

          2. Mantis Toboggan says:

            Riah I don’t know enough about the antibody levels to comment, but I think that since phase 1 and 2 have been done and safety seemed reasonable based on that data that you could use empty lipid nanoparticles as a placebo control. I guess the question would be what you learn from that, and as you pointed out, does that maximize safety?

            These general concerns are likely why there was a saline placebo control. I can see the argument some people made below for why you would use a different approved vaccine, but wonder if you would run into scalability issues. Are there 30,000 doses of a vaccine people don’t usually get? Could you use this years flu vaccine as a placebo?

          3. Marko says:

            ” Empty lipid nanoparticles seems like a good placebo to me. ”

            I agree , but I can understand why Moderna might prefer saline. Lipid nanoparticles are likely to induce some level of innate immune response , which might reduce the level of infections seen in your placebo group , at least for a while. If you’re hoping to show an efficacy signal as early as possible in the trial , saline is the safer bet for placebo.

          4. David E. Young, MD says:

            Who knows? I might get autoimmune hepatitis from scrambled mRNA? Or maybe hemolytic anemia? And even if it is a coincidence, I would still think it was the placebo arm scrambled RNA. And if so, I would ask… “did you really have to use that? You could have just used saline and here I am, sick, because you felt that you needed a placebo arm that makes my arm hurt and give me mild fatigued for a few days.” Some people would be litigious in that setting and both you and I know that there are hungry dog attorneys that would jump at that. Not in this country. Give the saline as a placebo and hope that the two groups are equally careful to avoid Covid (and not more because you got the placebo.). I have been very careful wearing masks, etc, but I would still be if I received the actually vaccine.

          5. Hopeful Layman says:

            @Mantis Toboggan — Remember, this is a double-blind test. If an actual active vaccine like the flu vaccine were used as the placebo, and then the person went on to actually get the flu vaccine for him/herself, wouldn’t that double dose be extremely dangerous?

          6. Thomas says:

            @Hopeful Layman, they could warn against that. and not use a common flu vaccine as control, but something else that is not regularly used in that age range. “You will be getting either the test vaccine, or a measles vaccine. You will likely not need to get a measles vaccine the coming 3 months, but if you had the need, you must drop out of the study.”
            Also, I do not think that repeat doses of vaccines are harmful in general?

          7. Hopeful Layman says:

            Thomas — you may be right about repeat doses over an extended period of time (e.g., someone who is now in his or her 30s got the measles vaccine while in elementary school) — I was thinking about someone who got the flu-shot placebo and then went to the pharmacy the next week to get his “real” flu shot. I was wondering if there might a problem with that.

        2. TabeaK says:

          Because scrambled RNA is going to give you a nice TLR mediated innate immune response that is difficult to predict and thus could be a safety problem.

        3. Thomas says:

          It makes more sense to use an existing veccine as a placebo.
          The placebo vaccine will have side effects too. And if the effect of the real vaccine is because of general immune system stimulation, the placebo vaccine will stimulate too.

          1. Marko says:

            Use the BCG vaccine as a placebo. You might find you don’t need any of these fancy-pants COVID vaccines at all.

          2. x says:

            Setting aside the caveat that these companies WANT to show efficacy as cheaply and strongly as possible, it would seem to be a good thing to be able to determine whether your COVID vaccine works better than a vaccine given for an unrelated disease.

          3. Thomas says:

            @Marko: it would be excellent to use BCG cvaccine as a control, as that could be “standard of vaccination” at this point in time.
            OTOH was BCG validated as (slightly) effective?

      2. Riah says:

        Are the Moderna and Pfizer really using only saline for the control group? I would really like to know as this will make the reason the Oxford trial gave me by email for using meningitis vaccine as the “placebo” very suspect

    2. Nick says:

      I’m in the Pfizer trial as well, I was one of the first 10 injected in my city! I’m <30 and I had fever and sore arm for a week, then joint/muscle pain and fatigue after injection 2. I'm not worried about safety at this point so much as I am young people prolonging the pandemic because they don't want side effects.

  6. Philip says:

    I am of two minds on the COVID-19 vaccines. I am looking into volunteering for a vaccine study at the same time I would not trust a vaccine coming to market this year. With Trump and his administration’s well documented lies about SARS-CoV-2 and the pressure they have put on the FDA and CDC how could anybody trust a rushed vaccine? For me to trust a vaccine, transparency is not going to be enough. When a vaccine is approved by a trusted FDA equivalent, then I will line up for a jab.

    Trump has done much worse than shoot a person on 5th Avenue. He has killed the public’s faith in the FDA and CDC. For those looking past the current pandemic, he has also murdered faith in the EPA, NOAA and other parts of our government. It will take decades to undo the damage Trump has done in just 4 years.

    I know this is a science blog and this is a political post, but when a politician like Trump actively tries to mute scientists and manipulate data for political purposes he has blurred the lines and must be called out along with his enablers (Scott Atlas for example: https://drive.google.com/file/d/1BLMrdGSsGEkuOvudxpm0iZPWOcTovKb_/view ).

    Derek, if this is over the top political, I apologize. If stating facts has offended a Trump supporter, good.

    1. M says:

      It’s hard not to be political on any topic in our current climate. I would be less pessimistic and say faith will be restored sooner than in decades, but who knows anymore. These things are as easy to predict as the stock market in a pandemic.

    2. Dark Day says:

      Philip, I concur 100%. Any vaccine that gets approved under Trump’s watch will be “claimed”
      by him as a victory — an immediate, probably fatal blow to its acceptance, especially in communities (e.g., the Black community, the Latino community) that have come to perceive him as virtually an existential enemy. For this reason, I honestly hope nothing is approved — in fact, I even hope the Phase III trials aren’t even close to completion — until Trump is gone. I realize that this would mean a couple more months (and, tragically, thousands more lives) lost, but the long-term alternative, I firmly believe, is even worse.

      1. Withheld says:

        >For this reason, I honestly hope nothing is approved — in fact, I even hope the Phase III trials aren’t even close to completion — until Trump is gone.

        What a fantastically bad and politically selfish take.

        1. Dark Day says:

          No, not “selfish” at all. I sincerely believe that’s the only way a vaccine will garner sufficient trust, especially among high-risk populations, for enough uptake to occur. Has nothing to do with politics, and that’s 100% sincere.

          1. MagickChicken says:

            Assuming Dark Day’s hypothesis is correct, I definitely agree with his conclusion – better that 50,000 die between November and January and we then get vaccines rolling out, than no one get vaccinated because they don’t trust it and 500,000 more die instead.

            It’s not selfish, it’s just math.

          2. Withheld says:

            Replying to (for some curious reason that thread is locked):
            “Assuming Dark Day’s hypothesis is correct, I definitely agree with his conclusion – better that 50,000 die between November and January and we then get vaccines rolling out, than no one get vaccinated because they don’t trust it and 500,000 more die instead.
            It’s not selfish, it’s just math.”

            But that’s not math. Those numbers are conjured out of thin air.

          3. Steven says:

            There are two sides to this. There are some people who will only trust the vaccine if Trump endorses it.

            I am fairly centrist politically. In my opinion, the pearl-clutching about Trump’s influence on the vaccine is largely a theatrical narrative promoted by his opponents. This is an emergency situation and it would have been a political issue no matter who was in charge. I wish it wasn’t Trump, but despite the number of stupid things he says he doesn’t actually do very much.

            It would be better for everyone if we all assume that CDC, drug companies, etc are acting with integrity until the results come out and we have some reason to suspect otherwise. Sowing suspicion at this stage is only growing the anti-vaxxer group.

          4. Dark Day says:

            Steven, I don’t doubt that in some cases you’re right about the pearl-clutching. But I can guarantee with 100% certainty that feelings such as I mention among the African-American community are very real and very pervasive. Folks already didn’t trust then U.S. medical system for reasons we all know; now, as I mentioned, many people have come to see Trump as virutally an existential enemy. That’s not political partisanship, it’s a deeply held conviction based on empirical evidence of things he’s said and done. So these remain things that need to be taken very seriously into consideration.

      2. blogreader09 says:

        You’re living in a dream world. Trump has unprecedented support in both the African-American and Latino communities. To count on “being rid” of him in a couple of months is a dubious-at-best appraisal of the situation.

      3. x says:

        You’re presuming that Trump loses in November. I wouldn’t count on it, considering his opponent. Do you want to wait four and a half years for a vaccine?

        Likewise, blaming Trump for an erosion of faith in government or scientific institutions is whitewashing the effect of gross mismanagement by members of both parties for years.

    3. Churlish says:

      Well stated and agreed.

      I used to regularly defend the FDA to highlight the importance of its reviews, and spoke very highly of its fundamental integrity. However, the clear evidence of its accelerating politicization during the pandemic means that I have very little faith in its decisions with anything regarding COVID, which is deeply troubling given that a minimally controlled epidemic is raging across the US.

      I now tell my friends and family to look to the actions of the EMA.

      1. Marko says:

        “I used to regularly defend the FDA to highlight the importance of its reviews, and spoke very highly of its fundamental integrity.”

        Let’s not kid ourselves here. “Fundamental integrity” hasn’t been fundamental at the FDA for a long time , at least since the PDUFA act in ’92 , when funding started coming from the pharma industry instead of from the US Treasury. Financial conflicts of interest have become rife on all the advisory committees since then , and are hidden from public scrutiny for the most part. The FDA works in the interests of Big Pharma , not in the interests of the people , because Big Pharma cuts their paychecks.

        Multiple whistleblowers have come forward to reveal this corruption over the years , and they’ve been treated like almost all other government whistleblowers have been treated , as Enemies of The State.

        The “old” FDA was indeed the world’s Gold Standard. No more. Trump has just accelerated a process of corruption that has been ongoing through Dem and Repub administrations alike , over decades.

  7. Harvey 6'3.5" says:

    Derek’s comment about seeing “detailed clinical trial protocols” and “the criteria for stopping any given trial for efficacy” really hit home. I think the companies could build a lot of good will by putting a few statisticians on TV to explain, with simple charts, how different scenarios might play out. Like, a 97% effective vaccine will likely require fewer data points than a 52% effective vaccine.

    1. Charles H. says:

      Unfortunately, that’s a problem. I don’t think a simple explanation that is honest is possible.

      Consider just the TM reaction. Nobody knows what causes most of the cases. But some reasons are known. Now a reaction occurs during a vaccine trial. How do you explain whether it’s related to the vaccine or not? The first one was called “caused by MS”. How certain is that, and how do they know? There are things involved there that have experts arguing with each other about at least the details and ISTM about the major causal elements.

      This is more suited to an article (or so) in a medical journal than to a TV show.

    2. loupgarous says:

      I just came through Hurricane Sandy. I, along with the rest of the Gulf South, was just treated to television broadcasts of a multiplicity of mathematical models for complex and ever-changing, highly-energetic phenomena that dwarf anything liable to happen inside a human body after injection with a vaccine. The “European models” of hurricanes and those generated by the US National Hurricane Center cannot fully be understood by lay on-onlookers.

      There are home truths, however, such as storm intensification as storms remain in one place that are more easily understood by lay audiences. It would be nice if CDC cultivated such more readily understood home truths and practiced presenting them to lay audiences.

  8. Eugene says:

    I keep getting the impression that people think Trump is actively reviewing the scientific data and ordering direct changes to the creation of the vaccines themselves for evil purposes. Like most politicians (and managers for that matter) when he asks questions, he will get a range of answers and will go with the most optimistic one available. The conclusion of any layman has to be after being told that the best solution to this crisis is the creation of a vaccine. The follow up to that conclusion is the sooner the better. Streamlining the process with multiple efforts and pouring money into it just makes sense. Any wasted money is a small fraction of the economic cost of the pandemic. You can also be sure that the FDA has teams of people on hand to review the data.

    1. Mariah says:

      Yes. Some people are against any hurried-up vaccine simply to spite Trump; as if Obama or Biden would never try to help get a Covid19 vaccine to market in less than five years.
      Derek is absolutely correct on the transparency points. And I was happy to see most of the major vaccine makers take a pledge not to apply for vaccine licensure before the science was done.

      1. Charles H. says:

        Pledges are nice, but they taste better when backed with evidence.

        So many organizations have been shown to be repeatedly lying, that words don’t convince. Evidence is needed. Preferably supplied by people who don’t have an iron in the fire. Transparency is a middle position. It still requires that you trust the honesty of the people providing the data, but it’s sure better than “trust me”.

    2. Withheld says:

      Right? It’s bizarre.

      FDA: “We may have a vaccine available by winter, or even fall at the earliest to combat this terrible pandemic thanks to an unprecedented effort by public and private institutions!”

      Scientific community: “OH NO!”

      1. Anonymous says:

        This is another example of trying to change the narrative to deflect from the real issues, Withheld. That’s not been the response of “the scientific community”. The response of those knowledgeable and experienced in such things has been “DESPITE an unprecedented effort by public and private institutions, reality does not work that you will know that your experimental treatment is effective and safe to use until you actually do the experiments, and no amount of railing will turn back time, make time go faster, or let you determine the likelihood of a 1 in 1000 event by counting 5 people.”

        1. Withheld says:

          You countered my “changing the narrative” by changing the narrative.

          No one in the FDA or CDC is trying to “turn back time, make time go faster, or let you determine the likelihood of a 1 in 1000 event by counting 5 people.” But there ARE many in the scientific community, and even in this very comments section, creating tremendous doubt in the FDA and CDC, and suggesting any vaccine should not be approved until a subsequent political administration. How exactly is that _more_ scientifically rigorous?

          1. Dark Day says:

            My own reasons for not wanting “this” administration to oversee the approval and rollout of a vaccine have nothing to do with my feelings about the FDA and the CDC; they have everything to do with the undeniable fact that a very significant percentage of Americans believe that Trump is trying to rush things for political purposes, and they believe that he will apply political pressure to get that done. Whether I, personally, think that the regulatory agencies will cave into that political pressure has nothing to do with the fact that many/most Americans seem to believe that they will — thus putting acceptance and uptake at a severe disadvantage.

    3. MagickChicken says:

      No, the impression we get is that Trump is *not* reviewing the data, just saying, “I don’t care what’s wrong with it or that you’ve only examined 10,000 of your 30,000 P3 recipients, get it out the door!”

      You know, like half the bosses in America. Hence our skepticism.

      1. Dark Day says:

        This is very, very real and needs to be taken seriously. If current trends continue, we could easiy end up with millions of unused doses of vaccine going bad on the shelves, as new cases and deaths continued to increase, and the economy — especially local economies –drifed further and further into freefall.

        https://news.yahoo.com/poll-number-of-americans-willing-to-get-a-vaccination-falls-as-fears-mount-that-trump-is-putting-politics-before-safety-203727770.html

        1. confused says:

          It’s possible.

          But I don’t believe these polls at all. Nothing about the actual polling… but what people say now about a decision they won’t actually be asked to make IRL for at least several months may not correspond with what they actually do when the time comes.

          Especially given that the media/social/political/etc. atmosphere in the US may be quite different in less than 2 months. We have a highly controversial election coming up after all…

          But more importantly, the vaccine will probably go to certain high-risk/high-exposure groups like healthcare workers first. So the “general public” is unlikely to be taking it totally ‘cold’ with only clinical trials.

          Also, I think the holidays will create a huge push for “normal life”.

          1. Dark Day says:

            . . . and a few weeks after the holidays, we’ll be paying for that “normal life” with new spikes in cases and deaths. The virus doesn’t care about our emotional, cultural, social, or spiritual needs; it’s a force of nature that just ACTS. And in this case, the things we need most in times of crisis — physical closeness, gathering together, etc. — are the very things that give it the opportunity to “act” with full virulence. I’m guessing the holiday season will set us back at least as seriously as Memorial Day and the July 4 weekend did.

          2. confused says:

            Sure – what I’m saying is that at some point the majority of people will collectively decide to live with the risk, and go on and do what they do knowing that there’s some % chance COVID will kill them (or someone else). We’re all aware we could die (or cause someone else’s death) in a car accident, but it’s rarely top-of-mind.

            Society used to function with much worse infectious diseases than COVID around, after all.

            And treatments will probably continue to improve (and the % of people with antibodies will continue to increase…)

            I am not sure how much Memorial Day/July 4th had a clear effect as distinguished from the general summer surge; in TX at least (my state) the summer surge is a pretty near-perfect bell curve, without clearly distinct peaks associated with specific events.

          3. Rudolf says:

            As you say, we will learn to live with risks which derive from the pandemic, as indeed we live with different risks across the whole of our normal life.
            The point is, is it more rational to accept the risk of potential but rare side effects or the risk of suffering death or long term harm from Covid.
            At the age of 73 although in good health, the answer is clear and a proper P3 involving several tens of thousand subjects and picking up an acceptable number of infections will reinforce that.
            We should be in that position with several candidates within several months.

      2. Dark Day says:

        Sorry about the dead-horsemanship, but once again, here is yet another example of how the current administration’s language and rhetoric has seriously impaired, and will continue to seriously impair, any kind of national initiative to get COVID under control. And, to be honest, even with a new administration in place in January, this could continue, with “red” states now being distrustful of any vaccine rolled out under a Biden / Harris administration.

        This is why I still believe that the best possible scenario is for no vaccine to complete Phase III, and certainly for no vaccine to be approved, until sometime after the November 3 election, if not the January 20 inauguration. That’s not political gamesmanship on my part; it’s just aknowledging a very unfortunate and very ugly reality.

  9. Steve Scott says:

    The Data Safety Monitoring Board in the U.S. reports to the NIH and is composed of an independent group of investigators.
    NIH’s Dr. John Mascola:

    “But the real important point is that for the phase 3 trial, there are no timesavers. One must enroll 30,000 people and watch them over months in a very rigorous, placebo-controlled environment. The NIH has stood up what’s called a Data Safety Monitoring Board for all the trials. That’s an independent group of investigators that will review all vaccine trial data periodically. They can see what the data are showing: Should the trial be stopped early because the vaccine is working? Is there a safety signal that raises concern?

    https://directorsblog.nih.gov/tag/data-safety-monitoring-board/

  10. Withheld says:

    The decline in folks who would not take a vaccine might not be so sinister as it seems.

    Aside from the traditional anti-vaxx crowd, many people might have determined by now that a) their personal risk is quite low based on age and health b) there is a decent enough chance of medicating out of a severe illness c) they may have already had it d) cases and death rates dropping nationwide infer less of a dramatic or escalating crisis than initially envisioned back in March.

    I figure a lot of folks aren’t really skeptical that it would work, or skeptical that it is safe, per se, more just skeptical that it is necessary to get to have a decent life, and might not be worth whatever rigamarole it requires to actually get the shots: (State Dept of Health: alright, first Monday in February we’ll start with the Latinx healthcare workers over the age of 80, next disabled veterans of color between 72-90, then NON disabled veterans, next all healthcare workers with conjunctivitis, ok now everyone over age 65 that does NOT like vanilla ice cream etc etc etc)

    1. Dark Dat says:

      But aren’t the results the same? Diminished uptake, less immunity, less chance to get control of the pandemic. In a way, the “reasons” don’t matter as much as the outcome.

      1. Withheld says:

        But this disease is not like Ebola/AIDS/MERS; it’s way less consistently deadly and transmits differently. This has been known since February; for some reason a lot of people get mild, barely recognizable illness that is recoverable in many folks. We can argue til blue in the face why, and about persistence of long term complications, and about herd immunity, but that is simply a fact.

        Another fact is that most humans are terrified of sudden death, but are ambivalent about long-term issues, whether it’s from eating too much red meat, alcohol, or any number of risky activities. One can read all about this inborn decision making process in Thinking Fast and Slow by behavioral psychologist Daniel Kahneman.

        Covid clearly has a massively massively worse effect on people 60+ and with certain preexisting conditions. I agree that such people should line up early and be prioritized for 100% vaccination. That way they will be protected from the 20-50yo who have chosen not to for whatever reason.

        1. grebs says:

          I agree. Until there is a bit of humility from those in goverment and scientific advisory positions who would rush to take the ‘magic bullet’ that allows everyone who hit the panic button to get away without admitting any mistakes whatsoever. The IFRs are trending towards seasonal flu, as I thought it might. FWIW i get my flu shot. Decicisons made in panic or to save face for those in power have proved this year to be bad decisions.

          In my opinion, the vaccines will no doubt be of low protective quality and the media will be watching for any adverse reaction/reinfection. This story will just go on and on until sanity prevails. The real risk here is a complete worldwide mistrust of vaccines and our business in general.

          1. Dark Day says:

            But the fact remains that until a vast majority of people — not just the elderly and other high-risk individuals — get vaccinated, we’ll continue to see high rates of new cases (some of which will, in fact, have serious health consequences even for the young and relatively heatlhy). As long as those number keep spiking (or even as long as they remain “stable” at high levels), Based on those numbers, mandatory restrictionjs will continue to impair virtually every aspect of our public lives and culture, to say nothing of the economy.

          2. WST says:

            “But the fact remains that until a vast majority of people — not just the elderly and other high-risk individuals — get vaccinated, we’ll continue to see high rates of new cases (some of which will, in fact, have serious health consequences even for the young and relatively heatlhy).”

            ..well, if people in risk groups get vaccinated, you will see in US what we seen in Europe, high infection rates (in <40) and practically no hospitalisations or ICU in this group, only very few elderly hospitalised in ICU and unfortunately also passing away.
            This builds an incredible pressure against the sanctions.
            In France, the quoted example is the aircraft carrier "De Gaulle" infection, 1700 seamen, 1200 infected, 20 with serious symptoms, no deaths.
            So, the proposed idea is that with elderly or weak populations protected (isolated or vaccinated), covid becomes a manageable disease with risks comparable to other everyday risks. Personally I think it's wrong, there are still too many unknowns and too many chronically ill, future mutations are also unknown, but there is a clear trade off that the politicians and society will be making.

          3. Dark Day says:

            WST, a lot of folks have predicted something similar in the U.S. That is, after all, more or less how we’ve approached the flu (anywhere from 12,000 – 60,000 deaths annually among the high-risk; mild-to-moderately severe symtoms in most others) until now.

            It’s difficut to know exactly how this will pan out here, since individual states have so much leeway, but I’m guessing that the public health attitude of “even one case is one case too many” may well prevail, and we’ll be masking and “distancing” and having a half-open economy, even if the vast majority of known cases are mild, until those numbers go down to diminishing levels. In fact, I wouldn’t be surprised at all if in coming years, we’ll be mandated to mask up and “distance” every flu season, as well.

          4. confused says:

            I really cannot see the US accepting masking and distancing for flu season.

            If some city/state did try to mandate that, they would soon have to stop because of economic pressures (since other cities/states wouldn’t).

            I think the same is likely to happen once a COVID vaccine is widely available (even if only flu-vaccine level efficacy &) and/or once deaths decline “below the epidemic threshold” and stay that way for a while.

            Fear of COVID will fade over time – new things are scarier than familiar ones. And very few people are really concerned about flu, and public health people won’t be able to *make* the public concerned about it.

          5. Dark Day says:

            Confused, even if “we” continue to accept the annual mortality rate from the flu, I can’t conceive of a similar thing happening with COVID. it may, as you suggest, depend on whether the very word “COVID” retains its power to terrify. But I also think that “mainstream” atttitudes toward public health have changed, and will continue to do so. It has become a moral, as well as a medical, issue to insist on protective behavior among those who aren’t at serious risk, because of the danger they could present to those who are. And unless we come up with a vaccine that’s 100% effective (an impossibility), at least a few elderly/at-risk people will continue to contract the disease, suffer excruciating symptoms, and die. These cases will be reported, and the pressure to eliminate or prevent as many of them as possible will continue to be extremely intense.

            If it’s a choice between a “new normal” of having our activities, our social gatherings, and our economies constrained, and a “new normal” of having significant numbers of elderly and frail people still getting sick and dying (or, alternately, being forced to “isolate” themselves), I think the first will be the one that’s chosen.

          6. confused says:

            I absolutely can conceive of it, and in fact think it is much more likely than the alternative.

            The word COVID will *not* retain its power to terrify. I give that 6 to 12 months maximum.

            Nor do I think there has been a *lasting* change in attitudes toward public health that will survive the end of a fear of COVID specifically — and if there did start to be one, applying the same thought process to flu would end it. There’s a reason that there’s been so much emphasis on distinguishing COVID risk from the flu… the public doesn’t care about flu, IIRC more than half the population won’t take half an hour to get a flu shot!

            More importantly, though… the COVID deaths that do continue to occur will *not* be reported in the same way current ones are. Once it’s no longer “new” it will no longer be “news”. In 2022, COVID deaths will not be any more visible than flu deaths.

            (I would actually expect a backlash, in the sense that the attitude will likely be that we over-reacted. I think when all is said and done there will not be a clear advantage in COVID deaths between nations with stricter vs less strict responses, at least outside East Asia/Oceania.)

          7. Dark Day says:

            There’s a real danger of social Darwinism coming into play here — “Oh, it’s just ‘those people’ dying, so how does thaf affect ‘us’?” And remember, it’s not “just” the elderly and people with pre-existing conditions who are at high risk. Communities of color and poor communities in general — areas which, by and large, are already ignored and shunned by most “mainstream” Americans — have been, and continue to be, devastated. America already looks the other way as gun violence, drug addiction, malnutrition, a vast array of chronic health problems, substandard housing and infrastructure, etc.etc.etc. plague “the ‘hood” and the “white trash” trailer park on the other side of the tracks — are we going to move toward adding COVID to the list?

          8. confused says:

            I don’t think that degree of disparate impact will be true once COVID is no longer “pandemic” but “endemic”. I think that has more to do with who is exposed than anything else – ie more in-person vs work from home jobs, # of people per household – and therefore is largely a factor of who can afford to self-isolate.

            So once no one is self-isolating…

            I mean, we don’t hear about that kind of thing happening with common colds or influenza. Everybody seems to be prone to get them.

          9. Michael says:

            Just want to echo Confused’s point about the future of “distancing” to fight the flu. There is just zero chance that holiday dinners/parties and winter spectator sports, to name two examples, will be banned forever post-pandemic to avoid the spread of the flu.

            Post-pandemic public health will instead focus on encouraging flu shots (and, if and when necessary, coronavirus booster shots). There will likely be messaging encouraging people to stay home when sick, and perhaps to wear a mask when symptomatically sick with the flu if one can’t stay home and needs to venture into an indoor public place.

            But there is no way that an ordinary flu season will lead to socialization bans. The ability to socialize in the future once the pandemic abates is going to be the #1 incentive for the vast majority of people to get a coronavirus vaccine (and the #2 incentive for the vulnerable). The upcoming vaccination campaign will fail utterly if the plan is for ongoing distancing to avoid the flue *even if* the vaccine defeats this virus.

          10. Dark Day says:

            Michael, I think you’ve hit on what should be the primary focus for any vaccination education campaign. Rather than finger-waving and “virtue signalling” (which, I believe, has often been how a lot of people have seen the masking and “distancing” mandates, whether fairly or not), the emphasis should be on what people have missed during all this.

            Do you miss holiday gatherings with your family? Do you miss going to see your son or daughter play basketball? Does your son or daughter miss playing in the school band? If you live near a professional sports stadium, do you miss seeing the games? Do you miss choir practice or sitting close together in church and shaking hands during the morning blessing? Do you miss your weekly bridge/poker/bid-whist club? Do you miss going out and having a drink and maybe dancing at a club after a hard week’s work? Do you miss sharing a friendly smile with a stranger, or with the bus driver, or with the person handing you a cup of coffee over the counter? (The list, obviously, is almost endless.) Want it back? Get vaxx’d! (And make sure the activities pictured, and people doing them, are 100% culturally diverse and/or appropriate for the specific audience you’re trying to reach.)

            A “carrot” approach will be much better than a “stick.”

          11. Marko says:

            If you want to use a “carrot” approach , just hand out a $100 bill to everyone who gets the vaccine. We’re going to need continued economic stimulus anyway over the next year or so , and none we come up with would likely be more equitable. If $3 trillion is too much , cut it by 2/3 and make it $1 trillion. Many , if not most , people who are now on the fence about receiving the vaccine would climb down for even just 35 bucks.

            Of course , you’d have to have a system in place to prevent abuse. Let’s see : I can go out and get a vaccine about once every hour , at 8 hrs/day and 7 days a week , that would be about………

          12. Marko says:

            Yes , $1000 makes more sense , when you do the math , which I botched in my post. At a thousand per , that would only be ~$330 billion for the entire country. Heck , in that case , make it $3000 per person.

            This country has been running on funny money and fumes anyway , so why not ?

          13. Dark Day says:

            It’ll never happen, but you’re right — it could work. (Just out of curiosity though, is there any historical precedence for something like this, either in the U.S. or elsewhere, where people were paid for doing something for the common good? I suppose returnable cans and bottles might be an example, but that was only a few cents per item — not really analogous to this.)

          14. Marko says:

            Well , energy companies are given big money subsidies to extract oil and gas for “the common good”. Many similar such subsidies exist , and the tax code is littered with such incentives that presumably contribute to that same worthy “common good” cause.

            However ,when you look for payments to the “common people” for doing the “common good” , the examples are fewer and farther between. Getting a nickle for a pop bottle may well be the most recent example.

          15. Dark Day says:

            CDC’s Robert Redfield said yesterday that mask-wearing will continue to be “more effective” than vaccines. Unless I’m misreading him, that seems to indicate that masking and “distancing” mandates may well remain in place indefinitely, even after the rollout of one or more vaccines next year. I suppose it could also have a negative effect on vaccine uptake, if enough people have come to accept masking and distancing as the “new normal” by then, and decide that it’s not wortht the risk getting a vaccine that isn’t as effective as what they’re already doing, anyway.

          16. Michael says:

            With all due respect, Dark Day, all evidence from every country in the world — from countries who have eliminated, or nearly eliminated, community transmission to countries completely swamped by the pandemic, and everywhere in between — is that people can’t or won’t accept distancing indefinitely. They immediately socialize when it’s safe, and some irresponsibly socialize when it’s not safe. All over the world.

            If a vaccine can be accurately and credibly demonstrated as safe and effective, and therefore can potentially be a ticket out of distancing, there’s no way that a critical mass of people will opt to keep on distancing. All evidence points to the fact that people everywhere are finding it harder, not easier, to distance the longer the crisis goes.

          17. Dark Day says:

            I hope you’re right, Michael. It may just be that I’ve been having conversations with the wrong people, but I have increasingly heard the argument that social media can, and will, increasingly replace real-world human interaction until eventually people won’t miss it at all. Here’s an excerpt from an e-mail that I received during one of these conversations:

            “People can still be physically together and they do. You just wear a mask and not be all up in people’s face. The Italians had a huge problem dealing with this thing, because they are so touchy feely. Being on Facebook a lot allows us to socialize anytime we want, at a distance. Just about everybody you know is on Facebook. It is a very very helpful way to stay connected to humans.”

          18. Dark Day says:

            More to the point, of course, is what will be mandated/required by public health policy makers. Predictions like this, from WHO’s Soumya Swaminathan, aren’t exactly the kind of thing to make us optimistic about the foreseeaable future (and, for what it’s worth, seem to challenge, if not contradict, a lot of what Dr. Fauci has been saying lately) —

            https://www.scmp.com/news/china/science/article/3101709/there-wont-be-enough-coronavirus-vaccines-return-normal-life

        2. wilhelm Cody says:

          A key difference is that, unlike with the origial SARS, a high percentage patients with SARS-CoV-2 have few or no disease symptoms while infectious. That makes taking temperature as a quick screen ineffective as a public health measure. It is performance art, not a winning strategy.

          While nucleic acid assays have become abundant, they not abundant enough nor rapid eough to catch most people with asymptomatic infections. They are unlikely to ever become so abundant. The solution is the approach promulgated by Dr. Mina: an inexpensive, rapid, easy assay with slightly less sensitivity but a much high probability of catching an infection while in transmission stage. Such an approach is the most effective way, short of barring everyone’s door with a officer outside, to controlling the spread until vaccines are available to build a herd immunity without killing as many people.

    2. Dark Day says:

      Also, to be honest, how many people are really “having a decent life” right now? Even people not directly affected (i.e., those who haven’t gotten sick, whose loved ones have remained safe, who haven’t lost jobs or housing, whose chidlren haven’t had their educations disrupted)
      have been seriously impacted in their everyday lives. Most places of public gathering (incl, houses of worship) are either closed or severely restricted; muzzling our faces and “distancing” ourselves from our fellow human beings remain a constant source of stress and emotional alienation (I’m guessing that the upcoming holiday season will be a time of terrrible depression, very possibly with tragic consequences, among people isolated away from family and loved ones); even if overall COVID case rates and death rates have leveled off or declined, the nonstop daily bad news takes a terrible mental and emotional toll. This has had a negative impact on people across the board; about the only ones who (arguably) haven’t been impaced are COVID deniers and the “Plandemic” tinfoil hat brigade. Look what happened to the Sturgis bikers — I’m betting that most of them aren’t in “denial” any longer!

      1. confused says:

        >>Look what happened to the Sturgis bikers — I’m betting that most of them aren’t in “denial” any longer!

        I don’t know that it’s that simple… or rather, I don’t think it’s helpful to divide it as “deniers” vs everyone else.

        Sure there are some genuine conspiracy theories out there, but there are a lot more people who acknowledge COVID is a real thing and in some cases deadly, but think that its severity for most people is too low to warrant the measures that have been taken.

        If people in the latter group get it and have a mild case (which the majority are), that might strengthen their view rather than disprove it.

        The secondhand “personal-experience” stories I’ve been hearing are largely ones that would make me less concerned, rather than more.

        That doesn’t really mean anything – it’s because I’m fairly young and know a lot more people close to my age than my parents’ or grandparents’ age. But people who haven’t looked at the statistics so much (and seen just how drastic the age effect is) might take similar stories as confirmation that it’s really no big deal.

        1. Dark Day says:

          ” . . . there are a lot more people who acknowledge COVID is a real thing and in some cases deadly, but think that its severity for most people is too low to warrant the measures that have been taken. . .[t]he secondhand ‘personal-experience’ stories I’ve been hearing are largely ones that would make me less concerned, rather than more. . . I’m fairly young and know a lot more people close to my age than my parents’ or grandparents’ age. But people who haven’t looked at the statistics so much (and seen just how drastic the age effect is) might take similar stories as confirmation that it’s really no big deal.”

          With all respect, Confused, please go back and see my comments about “social Darwinism” again.

          1. confused says:

            No, I’m not talking about that at all.

            What I’m talking about is that if someone gets COVID along with several of their close friends, and they’re all quite mild cases, they might decide that well it’s obviously no big deal… without really grasping just how *much* higher the risk is in *other* groups. People are often more strongly convinced by personal/social circle experiences than by statistics.

        2. Withheld says:

          Great points. Thank you.

      2. x says:

        I’ll commit the classic blunder of admitting to a “personal fault” on the internet…

        I have a very small social network, almost nonexistent, and have for years, due to a combination of night work, general curmudgeonliness, and the realization several years back that my friends and family were fools on their best day and assholes on all the other ones. I’ve felt alienated from society for much of my life and in recent years I’ve had little in the way of emotional support.

        Accordingly, I’ve observed the COVID-related emotional stress around me with a certain sardonic amusement. Is it so haaaaaard to not go to bars and parties, not see your friends and family? Welcome to my life – but I don’t remember anyone clamoring to make society more friendly and inclusive (to people in general, and particularly the various misfits and loners, I mean; not to certain lionized identities) before COVID, and I am sure I’ll see nothing of the kind afterward.

        In fact, living in the PNW, I see all sorts of sudden volunteerism and charitable donations of space and supplies for victims of the wildfires, whether they’re suddenly homeless, merely displaced by evacuation, or just in need of protection from smoke due to lung problems, etc. Someone lacking long term memory might be touched by the outpouring of help and sympathy, and be tricked into thinking that we are a kind and generous species that cares for one another – but I remember a time before COVID when the will to get the homeless into homes, the sick covered by universal healthcare, the poor supported and so on was tepid at best.

        When this is over, I believe society will go back exactly to the way it was, with no care for those who have no robust social network to bounce back into – or perhaps it’ll be even worse, since we will have been so charitable at this time that later we’ll have psychic license to be complete assholes and feel alright about it.

        Curiously, this will probably happen just about at the same time that we’re told that due to the economic effects of COVID and the cost of public spending, we’ll have to enter a long period of austerity, leaving the poor and disconnected to fend for themselves. And then no doubt another round of tax cuts and handouts to the “job creators”… it is a predictable cycle now.

    3. Kamil Pabis says:

      People may think that, but isn’t it nonsense? Not that we should expect lay people to make educated choices on such complex matters… The risk of getting COVID is high, at least in the US. The risk of COVID complications from the actual disease is many orders of magnitude higher than the risk of the vaccine .

      1. Withheld says:

        I’m not suggesting that the risk of Covid complications for the general population is somehow less than the risk of the vaccine. I’m suggesting that that’s not the only factor that goes into a rational person’s decision to get the vaccine or not. Most people could also give two shizas about whether the vaccine gets approved under by this administration or that administration. I would venture the _bulk_ of the decision is:

        “How can I get it? Where? Do I have to go to a hospital or special facility? Where is that? Is it out of the way of my commute? How expensive is it? Is it covered? Am I eligible? Oh, I’m not? Well when am I eligible? Why am I not eligible if this disease is super deadly to everyone….? Oh, I’m eligible next April? How do I make an appointment? Well, you know what, I realize it’s probably important, but the whole thing just sounds like a huge schlep and cases have been going down for 4 months now, so I guess I’ll just sit on it for now….?”

        Tons and tons of people DON’T get the flu vaccine even though it’s cheap, widely available, and extremely safe along the same lines of thinking. I’m not saying that’s “right” but it’s what people do.

        Contrary to some of the loudest voices here, most people _aren’t_ sitting in their basement cowering and waiting for a 100% Guaranteed Awesome Vaccine Approve By People I Like, they’re going about their lives as normally as they can because most people like their lives, and want to live normally. I don’t know why that’s so hard to grasp, but I suspect the quarantining has upended a lot of folks ability to conceive of what “normal” is supposed to look like.

        1. Dark Day says:

          Yes, both affordability and accessibility will be essential (as they already are for health care, and which is one reason so many Americans can’t don’t access health care easily).

          When a vaccine is finally rolled out, bringing it to people is essential to ensure compliance; we can’t assume that people will be able to get to the vaccine. I suggest that non-traditional venues such as church facilities, schools, fraternal organizations’ lodge halls, and other community-based locations should be repurposed as temporary vaccination centers whenever and wherever possible. (I seem to remember the gymnasium of my elementary school being used this way for either polio or measles vaccines when I was in second or third grade in the early 1960s, so this kind of thing is not entirely unprecedented.) This can also help reduce vaccine skepticism in communities where local institutions and venues are trusted more than “official,” often geographically remote, points of service. Also, we need to remember that it will take aggressive outreach and networking with local people to ensure that the most at-risk communities are included.

          Might I suggest that traveling mobile health clinics could also be a valuable part of the solution? They have been shown to be effective in other contexts, such as delivering health care to the homeless, and helping to provide medical and social services to at-risk mothers and children. In fact, if Bill Gates, Jack Dorsey, and other well-meaning billionaires are sincere in their protestations that they want to do all they can to assist in this crisis, they might do well to partner with the government in investing in, and equipping, a fleet of buses to serve as mobile health clinics to deliver vaccinations to poor rural communities in the U.S. They could also spur investments in clinics in underserved urban settings. The benefits could be immeasurable.

        2. Dark Day says:

          . . . and the point about eligibility is also a good one. We’re hearing that different populations — health care workers, the “frail” elderly, people with pre-existing conditions, and so on down to the “general” population — will be targeted for the various phases of the rollout. But, aside from licensed medical practitioners, let’s say, and people living in senior citizens’ facilities, how will in individuals know exacly when they’re eligible to partipate? Will a hospital orderly get first dibbs alongside the nurses and phsicians in the same hospital? If I’m over 60 and in good health, and someone else is 80 and in good health, will we both be grouped into the same “elderly” eligibility? Which pre-existing conditions will give one individual priority over another? Will otherwise healthy people in high-risk communities — poor communities, communities of color — also be prioritized? And then, after all this, at what point are all the “special” populations taken care of and the “general” population can be served? These abstractions and categories will have to be defined a lot more specifically than they have so far.

  11. AQR says:

    If someone participates in a Covid vaccine clinical trial (being dosed with the vaccine) and that vaccine ends up not being approved, does that mean that they will not be eligible to participate in the clinical trial of another vaccine candidate?

    Similarly, might participation in a clinical trial of an unsuccessful vaccine candidate compromise the efficacy of a subsequently approved vaccine in that individual? I can see that this might be the case if both the unsuccessful and the successful vaccines use the same adenovirus vector. What about other factors?

    1. debinski says:

      I am in the Pfizer trial and I know we are not allowed to get another investigational vaccine, nor would another trial accept you. I am also wondering about the second question but don’t know if there is any safety issue with getting another vaccine. I am pretty sure I got the placebo anyway (no side effects, not even a sore arm). The good news is that (according to what I read) people who are in a successful vaccine trial but got placebo are typically offered the real deal (on a priority basis) once the vaccine is approved.

      1. MrRogers says:

        Any insight on the timing for this? I might imagine that Pfizer et al would like to keep the trial going long enough to get a read on efficacy several months down the road, but it’s not clear to me if they’ll still have a placebo arm that long.

        1. debinski says:

          I don’t know what Pfizer thinks (perhaps they will continue to follow the placebo subjects for AEs after they get the active vaccine so they gain some safety data that way – but without a control group) but I found a draft plan for equitable COVId-19 distribution by the National Academies of Sciences, Engineering and Medicine that states “There is a long tradition in biomedical research of offering research volunteers priority access to interventions… Given this precedent the committee assumes that volunteer participants in vaccine trials will be vaccinated early regardless of the committees phased priority scheme because doing so is a typical standard of vaccine trial protocol.” It’s on page 80 of their report: https://www.nap.edu/read/25914/chapter/4#77

          1. debinski says:

            Make that “COVID-19 vaccine distribution” !

  12. Sulphonamide says:

    As per “anon” I’d be very grateful if anyone can shed more light on transverse myelitis…what I have read makes that sounds calamitously bad even as a 1 (or 2) in 30,000 event, at least for a disease that won’t (badly) harm (most) under 50s…?

    1. Marko says:

      Exactly , and there’s no way to pick up those low frequency , but important , adverse events if you stop trials too soon. Determining efficacy can be easy and fast if the effect size is large. Determining safety , especially for the low-COVID-risk younger age groups , requires elapsed time in large numbers of trial participants. There are no shortcuts.

      An EUA only for high–risk groups might make some sense , but only if it doesn’t compromise the continuation of the trials. I haven’t heard a good explanation of how that will be done.

  13. Alan Goldhammer says:

    The big question for me as a over 70 senior is which of the vaccines will be best for our age cohort. I got the double dose Shingrix vaccine over a year ago and get the high dose flu vaccine yearly. I also see the advantages of a vaccine/adjuvant combination. It is unclear right now which of the various delivery approaches is best. I live in a big metro area and cold chain storage is likely not to be an issue but I can see where it would be in more rural areas. I have some personal favorites among the different approaches but they won’t be available until early next year if everything goes right.

    Vaxart today announced FDA approval for their oral adenovirus vaccine construct which is good news. It is not part of ‘Operation Warp Speed’

    1. Marko says:

      The Vaxart candidate will be interesting to follow because it might provide some potent mucosal immunity. Plus , the oral tablet doesn’t require the sophisticated cold chain storage like some of the others. It might function as a nice “booster” for those who’ve already been vaccinated with one of the other candidates that are more likely to be first to market.

    2. Dark Day says:

      I’m over 65 and I share your questions/concerns, but according to an interview Dr. Fauci gave a few days ago, most of us probably won’t have the option of “comparison shopping” for a vaccine. It’s pretty much going to be a matter of which pharmaceutical chains in which parts of the country sign distribution deals with whom:

      “The companies are going to be advertising as to what the specifics and the specifications of their product [are]. I think it’s going to be more or less, Judy, something less sophisticated than — This one happens to be available in the supply place where you’re getting your vaccines, as opposed to you pick the one you want. It may be, if a certain pharmacy chain buys out and they become the ones that distribute it, fine, or if there’s another mechanism of distribution that the government is more deeply involved with, then that’s the one you’re going to get. I don’t think you’re going to be able to pick and choose like you would in a candy store.” (https://www.rev.com/blog/transcripts/dr-anthony-fauci-interview-transcript-september-8)

  14. Dark Day says:

    Marko, perhaps it’s the same with these?
    https://www.rev.com/blog/transcripts/dr-anthony-fauci-interview-transcript-september-8
    https://scitechdaily.com/single-dose-of-nasal-vaccine-against-covid-19-prevents-infection-in-mice-works-better-than-injection/
    . . . and this one I’m not clear about — I can’t tell from the news report whether they’re simply putting the already-existing vaccine in an inhaler of some kind and spritzing it into people’s noses and mouths, or whether they’re taking the same antigen and reformulating it into an entirely new compound. But at any rate, here it is: https://scitechdaily.com/single-dose-of-nasal-vaccine-against-covid-19-prevents-infection-in-mice-works-better-than-injection/

    1. Marko says:

      Yes , there seems to be increasing interest in the mucosal immunity strategy. This is from the link provided by Hopeful Layman in a comment below :

      “Imperial researchers are set to begin trials to assess the safety and effectiveness of two of the UK’s coronavirus vaccines in development, when inhaled into the lungs.

      The clinical team will compare COVID-19 vaccine candidates being developed by both Imperial College London and Oxford University, delivering the vaccines directly to the respiratory tract of human volunteers, by inhalation through the mouth.

      The UKRI-NIHR funded research, led by Dr Chris Chiu, head of the Imperial Network for Vaccine Research, aims to assess the safety and efficacy of administering the vaccines as airborne droplets inhaled by a volunteer, rather than an injection into muscle.

      The hope is that directly targeting the cells lining the airways – the typical point of infection for respiratory viruses – may induce a more effective immune response against the SARS-CoV-2 virus…..”

  15. Hap says:

    Getting a vaccine and thinking you’re protected from transmission might lead to more sickness and transmission if the vaccine doesn’t work, because you won’t be as concerned (as you would be if you knew that it didn’t work) about getting sick or getting others sick. If vaccine makers aren’t honest with other people about what is going on, there is less reason to trust that they are willing to be honest with themselves, and so more likely to circulate vaccines that don’t work so well. Dishonesty can thus get people killed both by people that won’t get the vaccine because of mistrust of the companies that make the vaccines and by people whose trust in the vaccine makers is misplaced.

    Either way, it ends the same – if people are not careful and honest (let alone actively dishonest) , lots of people get to die, both now (because of COVID) and later (because of all the other things dishonesty will break and make harder to repair).

    1. Dark Day says:

      At least to an extent, this will depend on the numbers. I can guarantee you that in the city where I live, even if there’s a widly available vaccine, until our case rate diminishes drastically, few (if any) of the restrictions on businesses and personal protective behavior will be modified. I don’t exactly know how low would be “low enough,” but simply having a vaccine on hand or even having proof that a majority of people got vaccinated will NOT be enough for any further “reopening” until those numbers drop.

  16. Withheld says:

    Why are some threads “locked,” without a reply button?

    1. Lappan says:

      I think it’s a limit on reply depth.

      1. Lappan says:

        …reply to a reply…

        1. Lappan says:

          …reply to reply to reply…

          1. Recursion says:

            …reply to reply to reply to reply…

  17. Bill says:

    I know Dr Fauci said in the event of multiple approved vaccines we won’t get to pick and choose. We will have to go with what the facility has chosen.

    I wonder. Currently I can get say a flu vaccine from the local hospital, any of several clinics and even chain pharmacies. In a world with four or five approved Covid vaccines, I’m guessing I should be able to do a little vaccine shopping.

    That possibility might prevent me from becoming an early adopter. Statistically unlikely the very first available vaccine is going to ultimately be the best for me. So maybe a little wait and see.

  18. HA2 says:

    Count me among group (4) here… I’m ok with vaccines in general. I’m even OK with an accelerated timetable on one, because of course we’re trying to rush things ASAP.

    But after what I’ve seen of the Trump administration, I 100% expect a mid-to-late-october announcement that a vaccine is ready – regardless of whether one actually is. I’ve also seen how no matter what nonsense Trump says, the apparatus of the US government immediately spins up to give it legitimacy, like the sharpied-on hurricane trajectory.

    So if Donald Trump announces a vaccine a few weeks before the election, and then the CDC or FDA back him up, I have to figure out what’s more likely – that the vaccine ACTUALLY passed trials, or that the CDC and FDA are now politically compromised. Or, rather… at this point I’m convinced that the CDC and FDA already are politically compromised – I have to judge whether they’re making the correct call in the case of this vaccine or not.
    And I just don’t know how I’d do that. I’m not an expert in this. I can’t read the trial results and figure out whether they’re adequate, whether the data’s been fudged or misinterpreted.

    I’m not planning on being first in line for this vaccine, I’ll probably wait for its approval in other countries first.

    1. Dark Day says:

      This is an honest question, because it concerns me, too: How will you react to a vaccine that completes Phase III and garners approval a few months AFTER the election, assuming that there’s a new administration in place by January? J&J, Novavax, and several others would potentially fit into this category. I’m hoping that even if a putatively “rushed” vaccine dies on the vine, others to follow might be more widely accepted. Or will the entire ambient atmosphere surrounding the very idea of “COVID vaccines” be so irrevocably sullied that no one will trust any of them? (This, by the way, is why I think it’s a very risky idea — simply in terms of good business, let alone the public health — for any company to even consider applying for approval, even EUA, before November is over. I think Bourla of Pfizer is making a serious mistake in promising results so soon.)

  19. DataWatcher says:

    I am increasingly distressed with AZ’s refusal to lay everything out on the table. Not only are they at risk of sabotaging their own efforts, they are fueling anti-vax fires that are already on the verge of burning out of control. Judging from the scientific response so far (at least as it’s being reported), their vaccine is probbly dead in the water already. They should get out before they pollute the entire pond.

  20. Hopeful Layman says:

    I know I’ve asked this question before, but I remain curious: What is the potential for these experiments with inhalable versions of some of the vaccines already under development?

    https://www.technologynetworks.com/tn/news/clinical-trial-will-test-inhalation-of-two-coronavirus-vaccines-in-development-340454

  21. Steve Scott says:

    UPDATE: This sheds a lot more light on the AstraZeneca trial halt in the U.S.

    https://www.cnn.com/2020/09/15/health/covid-19-vaccine-trial-astrazeneca-nih-fda-kaiser/index.html

    1. SteveM says:

      AZ no doubt is being evasive because they don’t want to scare away healthy trial volunteers as well as the general public if the vaccine is eventually registered and released.

      Would anybody here aware of the TM diagnosis now volunteer for the AZ trial?

      1. Dark Day says:

        Good point — nonetheless, I think it’s shortsighted of them to believe that this won’t have very negative consequences in terms of trust and uptake, if/when their vaccine is actually approved.

        It’s an unfortuate (posssibly even tragic) fact that in today’s world, we basically do our research (and everything else) under the glare of social media. In such an atmosphere, even legitimate and scientifically explainable anamolies can doom, or at least greatly hinder, an otherwise good and reliable research project. Imagine what would have been the fate of the Salk polio vaccine if Twitter et al. had been around when the Cutter Labs incident occurred.

        1. loupgarous says:

          Fortunately, Oveta Culp Hobby (SEC DHHS back then) made her neck available for political chopping after the Cutter fiasco. I honestly wonder if Alex Azar would Do The Right Thing under similar circumstances. To emphasize that that Mrs. Hobby was assuming responsibility in general terms and was not culpable (no pun intended) for the Cutter mess, Eisenhower urged her afterward to run for President on the GOP ticket in 1960.

          1. Dark Day says:

            Loupgarous, you are absolutely right. As difficult as it is to imagine a corporate “big-pharma” entity such as AZ (and, perhaps, given what’s being discussed in the “Monoclonal Antibody Data” thread, possibly Lilly as well) falling on its own sword for the common good, such a move would immediately restore a sense of legitimacy to the entire process. Let’s hope-against-hope that when the time comes, it will happen.

          2. loupgarous says:

            When I worked at Lilly, they generally didn’t minimize bad AEs. But I got there after the Oraflex fiasco, in which they couldn’t have behaved worse, having Lilly UK shove Oraflex fatalities under the run, so that people like my grandmother had to prove that Oraflex killed Americans, too.

  22. Jim Hartley says:

    Not an original thought, but Trump and Pence and their political appointees in FDA and CDC should receive the first doses of the first approved vaccine.

  23. DrivingInNeutral says:

    It’s quite possible I’m missing a clue here, but
    Is this not a sign of the trial being more, not less public than usual? I had thought that adverse or positive events don’t normally get released until the end of a trial?
    I will not be in a hurry to take a vx if I believe it was rushed, but what’s being rushed here?

    1. loupgarous says:

      Large “ethical” pharma firms publish AEs as they occur – generally, with little or no attempt to read the crystal ball. But there are those firms whose existence depends on one or two compounds in Phase III trials, the Sareptas of pharma commerce. For them, AEs aren’t all there is. There’s stock prices and albums filled with pictures of kids whose lives might at some point be improved by exon-skipping drugs and the like.

  24. Bill says:

    I’m personally not at all worried about Trump “having his way” with trials approvals. Not that it would be beneath him. But there’s just so much visibility on the subject the net effect will likely be the opposite. Good judgment may not be allowed to prevail even if justified. It could cost lives due to later than necessary availability.

  25. Marko says:

    It sounds like Caputo is kaput-o , so some good news , for a change.

  26. Rudolf says:

    Surely enough subjects will have been vaccinated for fairly solid data on the statistical incidence, or non incidence, of serious adverse side effects. At what stage the risk is justified will differ depending on the subject.
    For a fit 30 yr old in a non exposed environment, the risk of side effects would need to be closed down almost completely.
    For someone in the medical or care profession the calculation is very different. Unless we can vaccinate care workers we will probably see carnage again in care homes.
    Similarly with the active elderly, for whom Covid mortality rates are high, logic would argue for early vaccination.
    With regard to efficacy. Of course we want it to work. Hopefully better than the 50%.
    Surely this is a matter of deciding how many infections need to be seen across the P3 trial before unblinding it.
    Increasing the numbers, surely should reduce this time rather than increase it.

    1. Another Kevin says:

      I’m in an intermediate risk category. (It appears that the only real risk factor I have is age. I’m fit enough that a hike a week ago of 13 miles and 2500 feet elevation gained and lost was fun. No horrible habits (smoking, drinking more than about a drink a week, …). So while I’m no longer thirty, it’s quite possible that the risk of adverse events from the vaccine would be worse for me personally than the risk of contracting the disease.

      Still, I’d take it if there’s evidence that the risk of the vaccine in the population as a whole is lower than the risk of the disease. That’s because if I don’t take it, I’m running the risk of giving the disease to my high-risk wife, or to my daughter and through her to all her patients (and to some high-risk in-laws), and, Heaven forbid, to the members of my church (where I’ve suspended attendance for the duration of the emergency, even though there’s been a limited reopening).

      For me, killing someone else through my negligence would be a worse outcome than death from a vaccine adverse event.

      1. Dark Day says:

        I agree. For all the talk we’re hearing about how not wearing a mask is a sign of “selfishness,” I think it needs to be emphasized that eventual refusal to be vaccinated will be at least as selfish, if not more so. We owe it to one another — to the common good — to do everything in pur power to build up as much mass immunity as possible. Human lives; local, national, and global economies; and our overall mental/social/cultural health demand nothing less.

        1. confused says:

          I agree that it is selfish (assuming the vaccine shows sufficient efficacy), but I don’t know that that would be an effective argument.

          People who don’t think the vaccine will work, it’s just a political trick (or who think reported COVID deaths are mostly not actually caused by COVID and it’s just a cold/flu virus) wouldn’t *believe* that it was selfish… since they don’t believe it would actually prevent meaningful harm (to themselves *OR* others).

          The only other people that it might be meaningful to is young people who are at very low personal risk from COVID; but I think in general people who think the vaccine will actually work will be willing to take it.

          I think vaccine acceptance in the US will be a lot higher, when it actually becomes available, than current polls suggest. (I don’t see any way there will be mass distribution before December, even if an EUA does come out. After November I think the media/social climate will be different due to the election being over & having to do Thanksgiving w/social distancing.)

          The best thing local/state governments could do to encourage acceptance, IMO, is to commit to removing any distancing mandates after the vaccine rollout.

          1. Dark Day says:

            I agree it will probably be somewhat higher than the polls suggest, at least as they’re usually reported — the headlines normally frame the responses as a binary “Yes” / “No” — but then when you go into the data, you’ll fine a lot of “undecideds,” or you’ll discover that the question was whether the people would take the vaccine “now,” which isn’t the same as asking them whether they’d prefer to wait and see, first. From my own personal experience (hardly an official poll, I realize!) the “wait and see” feeling is pretty common, maybe even dominant. So if the first couple of phases of the rollout seem to be going well, the attitudes among the general population will probably improve.

            And although I stand by my “selfishness” argument, I also agree that self-interest, rather than “virtue signalling,” will be the best way to encourage uptake. Remind people of what they’ve lost, what they miss, what they want to get back to. (And for people with children, remind them of how much they’d like to see their kids want be able to get back to school in a “normal” way, including playing in the band, singing in the student choir, having proms and dances, etc.) Even people who don’t feel personally at risk will want to get their “normal” lives back, and if being vaccinated is the way, they’ll be more likely to do so.

  27. peter waldo says:

    What are the moral, ethical implications (and 500 other concerns!) of rushing to inject humanity with a DNA-altering vaccine (it is) and with nanotech components endorsed and research supported by DARPA? Is everyone under some kind of mind control lol? Really.

    1. Marko says:

      People have been wondering where you were.

    2. loupgarous says:

      Not to be snarky, but what, exactly is a live-virus vaccine but a DNA-altering device?

      1. Thomas says:

        I was on the understanding that a ‘normal’ RNA virus doesn’t touch the host DNA at all? and the BioNTech and Moderna RNA will definitely not have viral parts to to reverse transcripting and similar.

  28. loupgarous says:

    I can imagine Folger’s coffee and other flavorful beverages and foods commonly consumed in group settings being co-marketed with vaccines against SARS_2 in the same way as rationing was during WW2. As someone else here said, “carrot and stick”.

    1. Nanobodaddy says:

      Obvious choice for a marketing tie-in would be Corona beer.

    2. Hopeful Laymam says:

      Actually, at least in my city, Jewel-Osco supermarkets are offering a 10% discount on grocery bill totals to anyone who gets a flu shot at the store’s pharmacy. Might a similar incentive (maybe ratcheted up to 20% or so) work for COVID vaccines??

  29. An Old Chemist says:

    Pfizer sees ‘mostly mild to moderate’ safety profile in phase 3 COVID-19 vaccine study

    https://www.fiercepharma.com/vaccines/pfizer-sees-mostly-mild-to-moderate-safety-profile-phase-3-covid-vaccine-study

    1. Hopeful Layman says:

      Another “Layman’s” question (or two), RE: “Mostly” mild to moderate, with “rare” instances of severe side effects. When we’re dealing with an n of approximately 15,000, how is “rare” determined? Also, at what point does even the possibility of “rare” severe side effects become problematic when we take into consideration the fact that some of the people taking this vaccine will be elderly, medically frail, or otherwise unable to tolerate effects that younger, more robust individuals could probably handle? In other words, what’s “severe” for one might well be “life-threatening” or even “fatal” for another. How are questions such as these considered?

      1. confused says:

        Well, from my own (also lay) perspective, those same people are also at *overwhelmingly* higher risk from COVID. So a risk from side effects could be quite high compared to usual vaccines but still miniscule compared to the risk from COVID.

        IMO the real question about side effect risk is in the youngest age groups where the risk from COVID itself is very low so a large sample size would be needed to detect equivalent risks.

      2. a grad student says:

        I can at least address the classification of “rare” adverse events. The term ‘rare,’ along with everything from ‘very common’ to ‘uncommon’ all have specific thresholds for rate of occurrence.
        Rare = between 1/1000 and 1/10000
        Very common = 1/10 or greater
        The others fall in between those two in multiples of 10 (i.e. common is between 1/10 and 1/100). There’s also ‘very rare,’ which is fewer than 1/10000.

        I don’t feel qualified to answer the other part of your question about adjusting the risk/benefit analysis of said adverse effects on a patient-to-patient basis, although it is an excellent question imo. I think that ideally, a clinical trial will include that type of patient to determine exactly how serious a risk a given adverse event may be. If the risk is unacceptably elevated in a given group, the treatment (vaccine in this case) would be contraindicated in that population. Again, I’m out of my depth here, so take that with a grain of salt.

  30. Riah says:

    Sorry Derek this has nothing to do with this post but I can’t see where else to ask – so if you see this would you consider taking a look at the PCR test in a bit more detail? Or have you done that already ? If you do, the burning questions I have are 1.could a PCR test pick up people who are actually immune as cases because they may have viral fragments in their system still which the test then amplifies?
    2 If the answer to 1 is yes then how long can viral fragments survive?
    3 a higher number of amplification cycles could result in a higher number of covid positive “cases” so is there any standardisation between and within US states? If not it would be difficult to compare case numbers between states or places.
    4. As with 3 could some countries register fewer cases solely because they use fewer cycles?
    5. What number of cyles is appropriate? Virologists vary in their opinion between max of 30 and 35 with some saying that at 40 cycles virtually everyone will test positive!
    6. Is it feasable to use whole genomic sequencing (or culturing?) to carry out test samples so that you can quantify % of “false” positives (false in the sense there is actually no longer an active infection, no live virus but the test is positive). That way more accurate numbers comparable could be derived and comparisons would be more meaningful

    The UK government have just gone into meltdown over rising case numbers and it would be good to know how much of a solid basis there is for this using solely PCR tests.
    You probably have a whole list of your own to cover so no worries if this isnt near the top of your list……

  31. DrivingInTheSlowLane says:

    Wellll, it the risk of bringing some poly-ticks and its pathogen payload into the discussion, the preezydent made an announcement I’ll repeat:

    “We’ll have a vaccine by April”

    With phase III already started for several candidates, that’s 7 months out. That’s enough time for an honest phase III, data collection and interpretation.
    In other words, he just did the Right Thing.

    Color me surprised, and rethinking my previous assumptions.

    1. DataWatcher says:

      I’m not sure if he really did. I think he said that it will be available to “every American” by April, which isn’t as far off as his earleir guesstimates, but still two or three months earlier than most other predictions. But yes, I agree that he’s modified his message some. I’m sure he’s still assuming that he’ll be re-elected, and maybe someone got to him and made him realize that it wouldn’t look good for him if people thought a vaccine had been “rushed” under his watch, and so refused to take it.

    2. Marko says:

      Trump has no problem with the idea that a full-scale rollout will take until April , if not later. What he’s still going to push hard for is a pre-election announcement of approval for a limited rollout, via an EUA or “compassionate use” mechanism. I’m convinced this will happen. The rationalizations from the “experts” are starting to appear , even from Fauci , and will be coming at us fast and furious over the next month. Fauci was saying “12-18 months” back in the spring , now he’s saying Nov. or Dec. It’s only a matter of time before he accepts “end of Oct.” , setting up the October Surprise that surprises absolutely no one.

      1. Marko says:

        Per the NYT , today :

        “In a stunning declaration of authority, Alex M. Azar II, the secretary of Health and Human Services, this week barred the nation’s health agencies, including the Food and Drug Administration, from signing any new rules regarding the nation’s foods, medicines, medical devices and other products, including vaccines.

        Going forward, Mr. Azar wrote in a Sept. 15 memorandum obtained by The New York Times, such power “is reserved to the Secretary.” The bulletin was sent to heads of operating and staff divisions within H.H.S….”

        “…ormer senior officials with the F.D.A. and H.H.S. speculated that the intent was to remove rule-making power from Dr. Hahn, the F.D.A. commissioner, and to send a signal to President Trump that no surprises would come from the agency in the weeks before the election.

        “I can only conclude that this memorandum shows a lack of trust in the F.D.A. commissioner and other H.H.S. leaders,” said William B. Schultz, a former general counsel with H.H.S. and a partner at Zuckerman Spaeder, a law firm. ”

        https://www.nytimes.com/2020/09/19/health/azar-hhs-fda.html

        Trump is leaving no stone unturned. He’s going to get his vaccine announcement before Nov. 3 , and there’s nothing anyone can do about it.

        1. Dark Day says:

          I’m still convinced that this will absolutely annihilate any chance of sufficient uptake for the vaccine to do any good, even if it does turn out to be safe and effective. And if it greases Trump’s way into a second term, we can kiss goodbye any chance of a majority of Americans, especially “minorities,” accepting any subsequent vaccines that eventually come along. Fauci’s credibility will be shot to hell as well, so any reassurances from him will be pretty much ignored. We may have just been condemned to Covid Purgatory for the foreseeable future.

        2. Dark Day says:

          This will also put Biden in the untenable position of having to balance espressing distrust of the speeded-up approval process with his desire to encourage people to be vaccinated. If he does win the election, he’ll be confronted with the presence of one or more vaccines that he, himself, has expressed doubts about, but will now have to try to encourage Americans to take.

          1. DataWatcher says:

            Maybe I’m being naive, but it seems to me that the pharmaceutical companies must be keeping a close eye on this, and they realize that if they jump the gun and request early approval, they could end up with millions of doses of unused vaccines on their hands. It would be a wise business decision to hold off on any EUA request until after the election. Waiting another month and a half, until the end of December, might be the best plan. It will be unfortunate if this means that several thousand people who might have been vaccinated will get seriously ill or even die, but the alternative — tens of thousands, or more, getting sick and dying because they didn’t trust a vaccine they thought had been rushed out for political gain — would be even more horrible. There is no “best” alternative here, only the “least worst.”

          2. Marko says:

            The Pfizer CEO has said as recently as this week that they expect the first interim readout in October , and that if it indicates sufficient efficacy , they will file for regulatory approval. Then the decision falls to the Trump regulatory apparatus.

            It doesn’t matter how responsible or cautious the other vaccine companies are. It only takes one to give Trump his opportunity to declare himself “The COVID Slayer” , and if the Pfizer vaccine hits the numbers , he’s going to get that opportunity.

          3. confused says:

            I don’t think Biden will put himself in that position (especially as he seems pretty strongly favored to win). He can just say “we need to make sure a vaccine is safe” without going in the direction of calling any particular vaccine unsafe. He doesn’t need this issue to win the election.

            (IMO most people overestimate Trump’s election chances since 2016 was such a surprise. But that was a very different situation. 2016 was about frustration with the establishment, 2020 will be about a desire for return to stability.)

          4. Dark Day says:

            Marko, how do you think that would affect the public’s trust of subsequent vaccines? Would there be a lingering “Trump effect” leading to diminished uptake for quite some time (especially if Trump got reelected), or do you think it might not be as serious after January?

          5. Marko says:

            I think the public’s response will largely depend on how the media shapes their perceptions. Most people don’t follow vaccine developments like the readers of DL’s blog do. Still , I’m pretty sure a rushed approval will reduce confidence in general , to at least some degree , and that it may have a lasting effect , even beyond the COVID era.

            From my own perspective , any approval this soon , and potentially based on only 32 events , is lunacy in the context of a novel coronavirus and a novel vaccine technology like mRNA. I won’t be rushing to be first in line.

            Let’s say the interim look shows efficacy of 77% by meeting the target of 6 events in the vaccine group compared to 26 events in the control group. That means the vaccine will reduce your chances of symptomatic disease by a factor of about four. Now , suppose the vaccine causes a fatal outcome due to ADE in 1 of 20 ( or 50 , for that matter ) who are vaccinated but nevertheless acquire an infection. For most healthy people , the vaccine no longer makes any sense , and by looking at only 6 events in the vaccine group in the interim look , you’re not very likely to pick the ADE up. The PR would be a disaster once this became apparent after rollout.

            Admittedly , this is unlikely , but it’s not impossible. It’s why we do P3 trials , and why we don’t usually cut them off short in a situation like this.

      2. DrivingInTheSlowLane says:

        Instead of ‘Compassionate Use”, call it an Uber-Trial. That is, its rolled out to, say, 250,000 people max, who are in selected high impact groups. By that I mean people who can probably handle the vaccine (so maybe not the nearly-dead) or are likely to become super-spreaders should they catch it; that might be grocery store clerks or the church choir. The rollout size would be limited by how many can be monitored for side effects, and by risk containment.
        That would have the advantage of not undercutting the clinical trial.

        1. Dark Day says:

          We don’t even have church choirs right now, do we?

        2. confused says:

          To my entirely lay perspective, the obvious group of “relatively high-risk but not extremely poor health/extremely elderly” people would be healthcare workers.

          1. DrivingInTheSlowLane says:

            Of course, healthcare folks should be first, ahead of other categories. I just threw those out as examples of ordinary occupations which tend not to be noticed by the media but will have an outsize effect on increasing or diminishing virus transmission.

          2. Dark Day says:

            From what I understand, people in the meat and poultry packing industry are also among this number. And since a significant proportion of these idividuals are also people of color, if they were prioritized it might also make the beginnings of a dent in vaccine resistance in those communities.

  32. Hopeful Layman says:

    Looks as if the “mainstream” media are finally becoming aware of the refrigeration issue . . .

    https://www.nytimes.com/2020/09/18/business/coronavirus-covid-vaccine-cold-frozen-logistics.html

    Will the approval process take into consideration practical matters such as the logistics of shipping and distribution? If Pfizer or Moderna made it through Phase III successfully, might the powers that be wait a little while longer to see how their results stacked up against Astra Zeneca or maybe Novavax or J&J, , if their results were in by then, to try to ensure that an approved vaccine would also be as accessible as possible? Or will the decision be based solely on the data from the trials?

    For that matter, if one of the “Warp Speed” vaccines gets approved, and then another one gets approved a month or two later, is that later one basically out of luck? Or will the promised support still be there?

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