Comment by fasteddie31003 | Hacker News Reader

Comment by fasteddie31003 | Hacker News Reader

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I've been following Moderna's vaccine from the beginning. It was developed in 25 days from first virus DNA synthesis. https://www.modernatx.com/modernas-work-potential-vaccine-ag... but it's going to take maybe a year to be approved by the FDA. All phase 3 trials are looking good. I personally would take this vaccine right now but the FDA will not allow me to do this.

How is the FDA's reputation going to hold up when they approve all these vaccines a year or more after they were created and cost the lives of millions and trillions of dollars?

The FDA had no pandemic vaccine approval protocol which could have speed up the process. They could have used challenge trials with young healthy people. I can think of a pre approved process for mRNA vaccines where the delivery methods are approved but the only thing that changes is the mRNA payload.

I blame the government healthcare organizations for a lot of the impact from covid-19. First, they were anti-mask during the first major increase in the virus and now they are being overly cautious in approval of vaccines. They are way off on their cost - benefit math.

Unlike COVID-19 which is spreading a lot in the US (due to lack of coordinated government action) and which other countries have more or less stamped out and are controlling (Japan, Korea, New Zealand, Australia, Taiwan etc.), a vaccine will actually be given to something like 80-90% of the population.

So whereas the US has currently had a total of about ~10 million cases to date, this represents about 3.3% of the total population. There have been about 200,000 deaths so far, so the US case-fatality rate is about 2% - note, the mortality rate is most likely quite a bit lower overall since it's spreading so much. This is simply deaths vs. observed cases.

EDITED(got the math off by a factor of 10 here previously - at 0.01% fatality it's not 360,000 - that said, see comments below, actually establishing that in clinical trials is not easy): Let's suppose we rush through a vaccine that turns out to cause fatal complications in 0.01% of the population, and we give it 90% of the population. Straight up - we've just killed 36,000 people. But that's assuming that the complications are binary - but COVID-19's complications aren't binary, and neither would negative side-effects be. So we might kill a bunch of people, and injure tens of thousands more seriously. Or we might have inadequately diverse trials and miss a whole population of potential negative side-effects (a classic problem in a lot of trials: university aged students with the distribution of whichever university developed the product are over-represented in samples).

You cannot rush clinical trials. To even stand a hope of getting to 0.01% risks you need a population of at least several thousand in your trial. You need to monitor them aggressively because hopefully you have good data that whatever can go wrong will be slow enough you can intervene, but...there are always risks. Clinical trials can and do go badly wrong and people involved in them are taking a selfless risk for the betterment of the rest of us - and that's a very different proposition to declaring "this'll probably be fine" and not collecting the data.

I am all for finding a vaccine with the lowest possible fatality complications. I believe we should "rush" a vaccine during a pandemic by modifying testing protocols which will ultimately save more lives by speeding up the approval time. The FDA should have done challenge trials with a healthy population to better determine the vaccine's effectiveness.

I believe the silver bullet for future pandemics will be pre-approved mRNA vaccine pathways with the only change to the specific vaccine being the mRNA payload that targets the pathogen. Then testing could be a lot more straightforward and quicker which could end future pandemics.

I mean this would be the dream by AFAIK mRNA vaccines (like kind of a lot of this stuff) ended up not being as useful as it was hoped I believe?

> To even stand a hope of getting to 0.01% risks you need a population of at least several thousand in your trial.

Phase III trials don't run with enough participants to detect 0.01% effects with any confidence. These are generally found postmarketing, like Vioxx. In terms of vaccine harm, a badly behaved swine flu vaccine caused 3 cases of narcolepsy per 100k juveniles vaccinated. This effect simply would never be seen in Phase III trials.

Finally, beyond the raw CFR we need to consider other adverse outcomes from covid: cognitive impairment following mechanical ventilation and cardiac damage are two that really worry me.

Let's suppose we rush through a vaccine that turns out to cause fatal complications in 0.01% of the population, and we give it 90% of the population. Congratulations: you just killed more people to date then coronavirus has.

Might wanna check that math, dude.

Even with your preposterously deadly made-up vaccine, you’re only hitting about one month’s worth of COVID deaths.

Corrected the post above, but frankly, leaning straight on deaths wasn't my preference (just the numbers felt like they made the point clearly there). If you don't have the data, the reality is you don't have the data - you need thousands of test cases and time and monitoring to stand a hope of establishing it's not that lethal: The Oxford vaccine trial was paused in Phase II [1] when it looked "pretty good" because an extremely rare neurological condition showed up in two subjects.

[1] https://timesofindia.indiatimes.com/life-style/health-fitnes...

I think your math is off, if you gave a vaccine to 90+ percentage of people, say 300M, and killed 0.01% you’d be killing 30k people. This looks pretty attractive when your death toll is looking to rise to over 500k people. Eg if nothing changes until after January, 70 days , infection rate doubling every ~3 weeks, by then 300-400knew infections per day, lagging death rate of 5-6k per day, ~100k will die just in the 14 days of hard lock down assuming that happens day 1 of new president. Really hoping none of this happens and is just bad extrapolation but vaccine likely to save a lot of lives even with a 0.01% death rate.

You know I ran that through the calculator 3 times, before I posted it and did the wrong thing 3 times in a row...you're right (guess I shouldn't be posting at 3am).

I've amended the post's math - it's definitely not as hard a point, but the secondary consideration I didn't include was that it's also not an all or nothing proposition - a fatality rate from a vaccine is one thing, but even COVID-19 doesn't just have a fatality rate - it's got a much much higher "severe long term complications" rate. Which is also very much what you're looking for with trials.

Having things look good after 3 months in a vaccine trial doesn't tell you if they look good after a year necessarily - and all of this is really weighted against "a sensible response to limit the spread of the virus is possible, the US is just not doing it".

EDIT: The other possibility is that a vaccine that just straight up doesn't work very well would also make the situation worse - churn out millions of doses, get a limited amount of immunity in the recipient population, government is compelled to wind back "mechanical" spread prevention measures - and the epidemic cinders for a while and then rips through the population because everything thinks they're immune.

Regarding the effectiveness of the vaccine. A challenge trial where healthy people are deliberately infected after receiving the vaccine could very easily have answered this question. The FDA did not do this and should have IMO. I believe the UK is now taking the lead here and doing challenge trials.

I'd argue that doing that now, when we have a much better understanding of how to treat the virus, is quite a different proposition to the start of the year when we didn't.

Because if it doesn't work, you haven't had a doctor give someone something with unforseen side-effects: they injected them with a deadly virus and killed them (in the worst case).

Now we have treatments like Regeneron which the President received, which most likely made a very big difference in his fairly rapid convalescence - doing it when you have more plausible interventions if it doesn't work is quite different.

I mean all of this stuff is, relatively, going at lightning pace - if we have a vaccine early next year, that's what, 1.5 years between initial detection and immunization for a novel virus? That is breakneck pace.

Thalidomide.

Bah, I think that's a perfectly fair response. Arguing against drug trials is simply answered by history.

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