The US needs more urgency on developing a covid vaccine - Printable Version
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The US needs more urgency on developing a covid vaccine - stupac2 - 04-27-2020
I'm interested in getting some reactions to the arguments in this article: https://www.vox.com/2020/4/27/21231717/coronavirus-vaccine-development
I think most would agree with the second argument, originally from Bill Gates, for building up facilities to manufacture multiple vaccine candidates knowing that some will fail and it will "waste" money, because the wasted money is relatively small and speed is so important.
I'm more curious about the arguments around challenge trials, which I've seen mixed ideas on previously. It seems pretty persuasive to me, but I'm not involved with medical ethics at all.
RE: The US needs more urgency on developing a covid vaccine - 2006alum - 04-27-2020
Seems pretty common-sense to me, given the weight of the ramifications of finding a working vaccine ASAP. I would think the government would be able to provide insurance along the lines of workers' comp that would compensate for any long-term complications or death, and that it would not be that difficult to find volunteers willing to do it given that we have 20+ million who are suddenly unemployed.
RE: The US needs more urgency on developing a covid vaccine - burger - 04-27-2020
I agree strongly with the article.
The medical community needs to get over its ethical objections to challenge trials. Yes, they could conceivably cost lives. But they could potentially save far more. And if everyone involved is a volunteer and fully aware of the risks, I don't see why it's a problem. Philosophical objections to these sorts of things should be saved for non-emergencies.
We need a Manhattan-project level commitment to developing and producing a vaccine. Because of the costs involved, this can only be accomplished at the federal level. So, I'm not holding my breath that we'll actually do anything in a timely manner given the White House's lack of leadership.
RE: The US needs more urgency on developing a covid vaccine - Farm93 - 04-27-2020
(04-27-2020, 02:17 PM)burger Wrote: I agree strongly with the article.The risk, as has been presented by medical experts, is that you can create a vaccine that doesn't actually work or worse a vaccine that causes the body to overreact when the body encounters the virus resulting in death. That happens in animal trials, so just jumping to human use is a non-starter as short cutting the testing process could bring that risk to humans.
The medical community needs to get over its ethical objections to challenge trials. Yes, they could conceivably cost lives. But they could potentially save far more. And if everyone involved is a volunteer and fully aware of the risks, I don't see why it's a problem. Philosophical objections to these sorts of things should be saved for non-emergencies.
We need a Manhattan-project level commitment to developing and producing a vaccine. Because of the costs involved, this can only be accomplished at the federal level. So, I'm not holding my breath that we'll actually do anything in a timely manner given the White House's lack of leadership.
Liability is such a big deal in the USA. It is really unlikely a company can take a lot of shortcuts, even if the FDA permits it, for fear of getting sued by patients for years to come. Most companies that could afford to create doses at risk would never then double up their risk by pushing an untested vaccine for fear of losing their entire business in lawsuits.
The early manufacturing has some appeal, but the government would need to underwrite the effort. Many may recall that a recent administration was skewered for loans to solar panel and electric car companies even though those efforts ultimately produced Tesla. A government would need to support multiple efforts anticipating that many vaccines would not ultimately prove viable.
The companies in question would likely get the go ahead from the Trump administration, but would POTUS46 keep paying the bills? That would be a real risk for a company. My guess is most companies would not be that eager to play the game understanding the PR risks. Company G is successful. 6 months later companies H-Q all submit expenses expecting they will still get reimbursed. They would have to know that money might never be delivered.
Worse though would be what if all of the companies and viruses that the government backs all fail. You'd hate to be that administration or political party if the administration is out of office.
Put it together and a miracle fast track vaccine feels a bit like...
A miracle season change ending the virus or a miracle drug used for a different application ending the virus or a miracle use of a poison in the body ending the virus. I get the love affair with Americans seeking the easy way out, but it sure would be awesome for the federal government to really prepare citizens for the more likely scenario. A 3-4 year stretch where life as we knew it in 2019 is not available because a vaccine is not readily available. Most wars are not won in a few weeks, and our war on this virus is likely a multi-year effort.
RE: The US needs more urgency on developing a covid vaccine - stupac2 - 04-27-2020
It seems to me like "let's spend a lot of money and do a lot of research and do it as fast as we can" is in a far different league from those other ones, which really would be miracles. It hardly seems like an easy way out to do things like research multiple lines of attack, build out facilities for those, test them rigorously, etc.
Also, the point of the challenge trial is that you need to get this data somehow, exposing people to the pathogen on purpose is mainly faster than merely allowing them to go about their lives and maybe get exposed. And if there was some kind of adverse reaction then you'd be able to concentrate that risk in a much smaller number of people, and perhaps even stop the trial early, because the statistics are so much easier when you know everyone was exposed.
As I said before, I don't see why we'd accept sending volunteers off to war, but not challenge trials.
RE: The US needs more urgency on developing a covid vaccine - dabigv13 - 04-27-2020
I posted about challenge trials the other day and had some messages with BC about them. I haven't read the posted article. They are interesting and probably have some potential to speed things up, but they are not a panacea. Probably the biggest problem is if you're only enrolling healthy 20-30 year olds, you don't know if the vaccine will be effective or safe for older patients or those with other comorbidities.
I think a challenge trial with several vaccine candidates could be useful in determining which candidates to proceed with more widespread testing. But it won't give you the data you need to feel good about giving this vaccine to a big population.
RE: The US needs more urgency on developing a covid vaccine - oregontim - 04-27-2020
Shades of the Manhattan project. During WWII. National urgency of a different type. The best scientists of the day, relative to that topic, were brought together to solve the big problem. It was secret of course, so public opinion didn't matter. But it was national agenda and whatever they did worked.
RE: The US needs more urgency on developing a covid vaccine - burger - 04-27-2020
As for challenge trials, this organization (or website, at least) has registered over 4,000 volunteers to take part in challenge trials: https://1daysooner.org/ I didn't see any information about the age distribution of the volunteers.
I'd recommend checking out their history section. Challenge trials have been used on a number of diseases, some of which can be fatal.
RE: The US needs more urgency on developing a covid vaccine - BostonCard - 04-27-2020
I think there is a role for challenge trials, and though there may be some ethical issues, you can probably achieve equipoise in a low-risk population. That being said, while they are informative, I don't think they are a substitute for broad clinical trials, since challenges won't fully replicate the real-world way that COVID is transmitted. Some issues that a challenge trial can't tell you:
* What is the performance of the vaccine over time (in a challenge trial you typically perform the challenge at peak immunity)?
* Does the vaccine work with repeated exposures?
* Does the vaccine work with different types of exposures (large particles deposited in the oropharynx, small particles deposited in the lower respiratory tract?
* What is the vaccine safety in high risk groups (you probably can't ethically test a challenge model in patients with comorbidities or higher risk of death from COVID-19)
* How does the vaccine risk compare to the benefit, particularly in low COVID-19 risk populations?
To give you an idea, COVID-19 doesn't yet have a well-characterized IFR, but it's probably somewhere between 0.1% and 1%. For low risk groups (those under 40), the IFR is probably lower, such that those patients die due to COVID at a rate of between 1 in 1000 and 1 in 10,000. In order to prove the vaccine is safe enough in those low risk groups, you would have to show that harm due to the vaccine was lower than the disease it is preventing. In order to do that, as a rough guide, you need to test 3 times as many patients as the proportion of the outcome (the so-called rule of three). So, if the number of deaths in low-risk populations is 1 in 5,000, you would need to test the vaccine in at least 15,000 people to establish its safety.
That's not to say that there isn't a role for something like this. You might, for example, use a challenge trial to ungate vaccine deployment in very high risk settings such as nursing homes or for healthcare workers. In parallel with that, you would start a large conventional trial to establish traditional efficacy, as well as an open-label safety study (everyone gets vaccine) to make sure rates of adverse events in lower risk populations before you deploy it broadly.
BC
RE: The US needs more urgency on developing a covid vaccine - JustAnotherFan - 04-27-2020
(04-27-2020, 03:03 PM)stupac2 Wrote: As I said before, I don't see why we'd accept sending volunteers off to war, but not challenge trials.
To be clear, we lie to kids to get them to sign up to go into the military and then send them off to (usually) unjustified and unconstitutional wars for corporate profit against their will, and then we throw them on their ass when they are finished with their tours of duty unless they choose to navigate a 20-year career where they're sent off to die on multiple more deployments.
Challenge trials are far more ethical, honest, beneficial to the ones whose lives are put in the balance, and beneficial to society. It should be a no-brainer.
(Former military officer who has been deployed to a war zone in SW Asia)
RE: The US needs more urgency on developing a covid vaccine - stupac2 - 04-27-2020
Just to be clear, I don't see any of this as a panacea, just that our only conceivable way out of this without mass mortality is a vaccine, so we should be doing whatever we can to speed up that process.
Also, BC, wouldn't exploration of adverse effects be for a normal trial (presumably run at the same time as the challenge trial)? You don't need to expose someone to live virus to see if they react poorly to the vaccine itself. So you could conceivably use much smaller numbers of young, healthy people for the challenge trial and then the normal size/age distribution for the standard trial.
RE: The US needs more urgency on developing a covid vaccine - dabigv13 - 04-27-2020
Phase I trials are ongoing to test for safety already. The first one in the US went in March 16th at Kaiser in Washington.
https://about.kaiserpermanente.org/our-story/health-research/news/first-covid-19-vaccine-trial-at-kaiser-permanente-washington
RE: The US needs more urgency on developing a covid vaccine - Mick - 04-27-2020
(04-27-2020, 06:27 PM)JustAnotherFan Wrote:(04-27-2020, 03:03 PM)stupac2 Wrote: As I said before, I don't see why we'd accept sending volunteers off to war, but not challenge trials.
To be clear, we lie to kids to get them to sign up to go into the military and then send them off to (usually) unjustified and unconstitutional wars for corporate profit against their will, and then we throw them on their ass when they are finished with their tours of duty unless they choose to navigate a 20-year career where they're sent off to die on multiple more deployments.
Challenge trials are far more ethical, honest, beneficial to the ones whose lives are put in the balance, and beneficial to society. It should be a no-brainer.
(Former military officer who has been deployed to a war zone in SW Asia)
+1
RE: The US needs more urgency on developing a covid vaccine - Farm93 - 04-28-2020
(04-27-2020, 08:35 PM)stupac2 Wrote: Just to be clear, I don't see any of this as a panacea, just that our only conceivable way out of this without mass mortality is a vaccine, so we should be doing whatever we can to speed up that process.I think everyone likes the idea of speeding up the process. The catch is the nation's collective understanding of the timeline, success rate and costs are all off.
Also, BC, wouldn't exploration of adverse effects be for a normal trial (presumably run at the same time as the challenge trial)? You don't need to expose someone to live virus to see if they react poorly to the vaccine itself. So you could conceivably use much smaller numbers of young, healthy people for the challenge trial and then the normal size/age distribution for the standard trial.
The all in effort probably is needed to get a vaccine before end of year 2021. That would be an epic accomplishment, but as the USA citizens have been told it could happen much earlier a Dec 2021 result likely would be seen as a political loser with hearings and audits for years.
The chances that the all-in effort works is not really 100%. People think Manhattan project, moon launch, etc. But this acceleration could land in flying car or underground freeway territory. Spend the money and get nothing is a possibility, and again I don't see this current administration walking the citizens through that possible result on the front end.
It is easy in April 2020 to say let's do everything when nothing seems to be available, but will taxpayers sing the same tune in 2022? Especially if other countries developed solutions for a fraction of the costs?
My guess is the GOP's preferred strategy will be to let private companies chart their own path with businesses conducting their own business risk assessment. The profit potential and PR benefits are clear enough for most companies without the government trying to pick winners.
RE: The US needs more urgency on developing a covid vaccine - Snorlax94 - 04-28-2020
Farm93 Wrote: My guess is the GOP's preferred strategy will be to let private companies chart their own path with businesses conducting their own business risk assessment. The profit potential and PR benefits are clear enough for most companies without the government trying to pick winners.
Gilead Sciences, makers of remdesivir, make about $22 Billion in revenue each year. A Merrill analyst sees remdesivir sales being $2.5 Billion for covid-19, total, for its lifetime. So, best case, it boosts revenues about 10% for one year — *IF* IT WORKS.
Additionally, drug firms don’t generally invest a ton inventing new drugs vs. marketing existing ones, and reformulating or repurposing existing ones. Given the federal deficit this year may be around $5 Trillion or more, it seems like they could spend a few million or billion to encourage more research to increase the odds of shortening the recession. If we can shorten the recession by just 1 quarter, that could boost 2021 gdp by hundreds of billions of dollars.
From the Motley Fool:
Some analysts, such as Geoff Meacham of Bank of America Merrill Lynch, said in February that the total upside for remdesivir isn't that impressive and won't do much to change Gilead's long-term financial outlook. He predicted that total COVID-19-related remdesivir sales would reach a one-time figure of just $2.5 billion.
The optimal dosing schedule for remdesivir is still uncertain, with current clinical tests experimenting with a five-day and 10-day treatment schedule, although doctors have had success in administered a single large dose of the drug as well. Analysts from Morgan Stanley predicted that the company could charge as little at $260 per treatment plan in China, which would be the main market for remdesivir (at least right now). If one assumes that the nearly 18,000 currently diagnosed COVID-19 patients in Hubei province all take a full treatment plan of remdesivir when (or if) it becomes available, that adds up to just $4.7 million in potential revenue if the virus doesn't drastically spread further.
RE: The US needs more urgency on developing a covid vaccine - BostonCard - 04-28-2020
(04-28-2020, 11:31 AM)Farm93 Wrote: My guess is the GOP's preferred strategy will be to let private companies chart their own path with businesses conducting their own business risk assessment. The profit potential and PR benefits are clear enough for most companies without the government trying to pick winners.
https://www.medicalcountermeasures.gov/app/barda/coronavirus/COVID19.aspx
$456,237,081.00 to Janssen (J&J) to "Support development to licensure of a vaccine to combat COVID-19 using Janssen’s established Adenovirus 26 platform."
$430,298,520.00 to Moderna for "mRNA based SARS-CoV-2 vaccine encoding a pre-fusion stabilized Spike protein"
$30,775,336.46 to Sanofi for "Recombinant SARS-CoV-2 spike protein with transmembrane region deleted produced using Sanofi’sFDA-licensed seasonal influenza vaccine Flublok® facilities"
That's just BARDA's funding of vaccine development. They are also funding diagnostics, therapeutics (disclosure, I work for one of the company's whose product is being funded).
BC
Some more news on vaccine development:
https://www.wsj.com/articles/pfizer-coronavirus-vaccine-could-be-ready-for-emergency-use-by-fall-11588094064
(might be behind a paywall)
Quote:Pfizer said Tuesday it will begin testing of its experimental vaccine in the U.S. as early as next week. On Monday, Oxford University researchers said their vaccine candidate could be available for emergency use as early as September if it passes muster in studies, while biotech Moderna Inc. said it was preparing to enter its vaccine into the second phase of human testing.
Specifically about Pfizer's effort:
Quote:New York-based Pfizer is working on vaccine candidates with Germany’s BioNTech SE. The shots are based on an emerging gene-based technology known as messenger RNA, or mRNA, which carry instructions from DNA to the body’s cells to make certain proteins.
Testing of a vaccine, which has already started in Germany, could start in the U.S. as early as next week if health regulators sign off, Pfizer’s Mr. Bourla said. Results from the study could come as early as next month, he said.
If further testing also proves successful, Pfizer could start distributing the vaccine on an emergency basis in the fall and receive approval for widespread distribution by year’s end, Mr. Bourla said.
BC
RE: The US needs more urgency on developing a covid vaccine - BostonCard - 04-28-2020
More on the Oxford vaccine.
https://www.nytimes.com/2020/04/27/world/europe/coronavirus-vaccine-update-oxford.html
Don't get too attached to any one effort, but with enough shots on goal, hopefully one will be successful.
BC
RE: The US needs more urgency on developing a covid vaccine - stupac2 - 04-28-2020
(04-28-2020, 06:36 PM)BostonCard Wrote: More on the Oxford vaccine.
https://www.nytimes.com/2020/04/27/world/europe/coronavirus-vaccine-update-oxford.html
Don't get too attached to any one effort, but with enough shots on goal, hopefully one will be successful.
BC
And that's the whole point behind parallel development of manufacturing, hopefully one of these works (we're pretty Fucked-with-a-capital-F if they don't) so you may as well bet on all of them. What do you think the shutdowns cost us, a few hundred billion a month? Every day you gain is worth billions. The ROI here is insane, we should be doing whatever we can to speed it up, if it's at all plausible it should be greenlit.
RE: The US needs more urgency on developing a covid vaccine - Goose - 04-28-2020
Possible interesting link
https://www.biospace.com/article/oxford-university-s-jenner-institute-ahead-of-the-curve-on-covid-19-vaccine/?utm_campaign=GenePool&utm_source=hs_email&utm_medium=email&utm_content=87086508&_hsenc=p2ANqtz-9CjGsw-QjyE_Z3G4SeBu7QKSpPMDfv__ibFy9vjfMZP3BEVCDXb9b8qRcd49tLQAPkKxo2w0DJzoq-MZqI_yIVz15kbg&_hsmi=87086508
RE: The US needs more urgency on developing a covid vaccine - chrisk - 04-28-2020
There is not likely to be much profit in a COVID-19 vaccine, because no one company would be in a position to hold Trump and the country hostage.
https://www.statnews.com/2020/04/21/vaccine-quenches-covid-19-what-will-pharma-want-in-return/
But this article points out the pharma industy would have tremendous leverage in discussions on price controls over the industry.