We keep arguing about the wrong things
Matt Yglesias has a very perceptive tweet:
There are various ways of reading this tweet, but here’s my take:
There are pros and cons of the herd immunity strategy.
There are pros and cons of challenge trials for a vaccine.
Perhaps we should do both, perhaps neither.
But the case for challenge studies is clearly far stronger than the case for herd immunity.
Every criticism of challenge studies applies 10 or 100-fold for herd immunity.
People like Alex Tabarrok keep banging the drums for challenge studies, but is anyone paying attention? (Maybe its too late.)
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19. October 2020 at 04:29
Scott,
it’s an agency problem. Herd immunity is, passively letting infections happen. No guilt assigned, no identifiable liability. Challenge trials is, actively designating who gets infected. Legally identifiable guilt and liability in case of a mishap. Compare, firebombing a city and killing 20,000 women and children. Act of war, not guilty. Pilot gets downed in enemy territory, sees a woman and child and kills them by throwing stones at them without provocation. War crime.
19. October 2020 at 06:17
I have to agree with the above reasoning. As an individual I can’t decide to do something like human trials. But I can decide it’s not worth sacrificing 18 months of life versus getting the virus – so when the government couldn’t speed things up we individually chose herd.
IMO this isn’t an American problem. Everyone I know I believe would support human trials. But no government would approve them.
19. October 2020 at 08:58
mbka, Yes.
Sean, Yes, but where are the “Great Barrington” groups calling for rationality on challenge studies?
19. October 2020 at 10:27
I have a hard time seeing maintaining isolation until we have a vaccine as “sacrificing 18 months of life.” It’s not.
Yes, I’d like to travel. Go to a restaurant. Go see the ballet. I can’t do any of these things right now. But the truth is, these are all mere wants, and there are plenty of other things I can do with the time instead; I’m writing fiction. I’m cleaning out the house of junk.
The sacrificing is greater on those whose livelihoods require the regular mingling of people, of course. But that’s where the government should step in to ensure that it’s not an undue hardship. But still, there’s plenty to do around the house with a bit of imagination; this is not lost time.
19. October 2020 at 11:31
A speculation—even as “cases” have quadrupled since May 15th—and many think active cases may be 10x or more than “confirmed”, it is rather interesting that 7 day moving average of “counted deaths” has a daily range of 4302 (May 30) to 5990 (Aug 14th). I don’t know the monthly range but mean appears to be around 5200 (estimating the area above and below 5000) and today it is 5261.
Maybe it goes lower—-maybe it takes another few years—-but this looks like “herd immunity”–in the sense the deaths are almost a constant.
Of course, the are dozens of offsets that exist, including seasonal effects. Some places may have hit their constant, others may not yet have reached it from above or below. But if 10x is close to true, than this may be where herd immunity lies.
Plus we need to actor in age—which is hard to do with 7 day averages. Without antibodies or vaccines, its hard to believe we will get much lower.
I also don’t think “shutting down” has any effect at all when we constantly open and close—-stay open
19. October 2020 at 11:42
Scott,
I didn’t fully understand this subject at the beginning either, but as I understand it today, challenge studies simply make not much sense. It’s not a relevant problem right now to test whether the most promising vaccines work or not, especially regarding a disease as widespread as Covid-19. Challenge studies simply aren’t needed right now.
Take the Phase III studies, for example. It’s not just about effectiveness, but also about rare but serious side effects. And for these rare but serious side effects, you need two things more than anything: a lot of people and quite some time.
Challenge studies won’t help you with these time-consuming trials at all.
I hope for challenge studies, if a pretty deadly virus becomes endemic. Then things might look different, because then rare but severe side effects simply won’t matter that much anymore.
Let us not forget that this disease would have been under control long time ago if American and European politicians had reacted correctly and if not so many people from the American and European continent refused to do really simple things such as wearing a mask every time they had contact to other people.
19. October 2020 at 12:19
Christian List gets it right in his post. I spent my working career in the pharma industry in regulatory affairs and drug safety. Human Challenge studies cannot address vaccine safety particularly for the ‘rare’ 1 in 10,000 adverse event. The major reason for large subject numbers in vaccine trials is to pull these side effects out. If there is widespread pathogen in the real world, it’s easy enough to take the trials to those areas (almost every company has trials in Brazil tight now). Chinese vaccine trials are in the Middle East and Indonesia. India have their own going on as well.
The Human Challenge Study effort was well meaning but unneeded effort.
19. October 2020 at 12:23
IVV, I’d add that even Swedes have some restrictions on things like large groups and international travel, whereas even here (in OC) we can go to restaurants and movies. So while there are differences, it’s not so extreme as between living and not living.
19. October 2020 at 12:26
I should have added that we have no idea what the infection rate is for herd immunity. We know from the anti-vaccine ‘experiments’ that whooping cough, measles, and chicken pox have a herd immunity requirement of about 90%. Certainly we hope this is not the case for SARS-CoV-2. We also don’t know what the true mortality rate is for the virus. I’ve read most of the herd immunity papers and there are estimates from 25-75%. I believe the mortality rate will settle down to at or slightly above what was seen in the 1957-58 Asian Flu outbreak (0.3% was observed in that case). If we assume 505 infection for herd immunity, it’s easy to do the mortality number if nothing is done: 330M people * 0.5 IR * 0.003 MR = 495K deaths. Anyone can play around with this equation because of its simplicity. Several of my epidemiologist friends and I believe that this is the likely real scenario.
It is a sobering number compared to the normal seasonal influenza mortality.
19. October 2020 at 12:27
Christian and Alan, You want to do both. I’ve read that this is being held up on efficacy grounds, not safety, and that as soon as the data clearly shows efficacy, countries will move ahead.
We certainly have enough safety data already to give it to the over 85 year old group, for God’s sake! And we won’t have enough vaccine to give it to everyone at first anyway.
19. October 2020 at 13:24
“We certainly have enough safety data already to give it to the over 85 year old group, for God’s sake!”
We don’t have that information. Individuals over the age of 60 have diminished immune systems and this is not addressed by HCTs which would be given to much younger subjects. From a HCT one would not know what the right dose is for older people or whether that higher dose leads to more and perhaps different side effects. Look at the seasonal flu vaccine. Those over 60 are supposed to receive the high dose vaccine. Similarly, the new Shingles vaccine in enhanced by both adding a dose and using a highly potent adjuvant. The RNA/DNA vaccines do not use an adjuvant and the one I’m looking forward to seeing the results is the Sanofi/GSK effort that uses the Spike protein and the GSK potent adjuvant.
The one vaccine that might be best is the inactivated virus vaccine that China is testing. It would be the height of irony is that turns out to be the best one.
19. October 2020 at 13:49
Scott,
I agree that the vaccines should be released for volunteers who want to be vaccinated. They must be openly informed about the benefits and risks, and then let people decide for themselves.
From how I interpret the reports, Russia and China have sometimes simply skipped Phase III. The West should not be so arrogant, there is no right or wrong here, it’s just a question of how much and what risk you want to take. The West always pretends not to take any risk, but of course it is also a risk if you vaccinate later.
As you as an economist know better than anyone, most Westerners are no longer able to factor in the price of not doing something. They count “not doing something” as “nature running its course”. With that mind trick they tell themselves that they are off the hook.
I don’t believe that efficacy is the problem at the moment. Some of the media reports are simply not well written. Efficacy should not be the problem. And safety, as demanded by the American and European authorities, takes time.
In Europe I am very sure that safety is the reason. The two vaccines from Germany, for example, are effective, but they still have to prove their safety for cases aboth 10,000.
You could do a challenge study, say 100-1000 people, vaccinate all of them, infect all of them, then you would have good data about efficacy. But if, for example, you infect 1000 people, you would also have to deal with, say, one dead test person and some people in intensive care. You have to test old people as well, so the death rate is going up even more. This is not ethical. And it does not give you the safety data that we need.
Phase III trials answer both questions together, you don’t kill anyone directly, and the time-limiting factor is safety, not efficacy. So I fully understand why they are not doing challenge studies right now, there is no benefit.
I was also not fully aware that there is a good enough alternative to challenge trials already: In Phase I and Phase II, you simply measure the antibodies, which give you pretty good indications of efficacy without even infecting people. It’s not perfect of course, but it’s good enough.
In case of a really disastrous mass-killer virus, comparable to the plagues of ancient and medieval times, they would (hopefully) skip several tests:
Create a vaccine with the new mRNA method, test the antibodies on 100-1000 people, and then basically just screw safety for now and run with it.
You can do this with several different vaccine lines. But again, you see that even in this extreme case one doesn’t even need a challenge trial. The “challenge trial” is simply all the volunteers in the population who are lucky enough to get the vaccine first. What would be the point of the challenge trial? Challenge trials seem to be obsolete right now.
I agree with Alan that the Chinese vaccine is interesting, because it is different. It follows a time-consuming, more risky regardings side effects, but well-established method, whereas the Western methods in Phase III so far mostly seem to be based on mRNA. A completely new method, really interesting, and maybe the future not only in the field of vaccines, but also for many drugs and therapies, but the method is so new that not a single mRNA vaccine has ever made it to market so far.
19. October 2020 at 14:31
Robin Hanson I believe called for challenge trials early and I believe there were some groups backing the idea. They do exists but maybe not as large of scale.
I have no idea why someone like Bill Gates didn’t back juman trials to speed up vaccine trials by 3-6 months.
Russia came closest with the earlier vaccination trials.
And Hanson also backed variolation for the young which I gladly would have participated in.
19. October 2020 at 15:32
Alan and Christian, As with everything else, you weigh costs and benefits. There are risks in vaccinating 85 year olds, and risks in not doing so.
Sean, The UK did some challenge studies.
19. October 2020 at 16:29
Christian,
really good and well-reasoned points.
To my earlier comment, I just realized that ethically speaking, “challenge trials vs herd immunity” is a trolley problem. Only difference is that the people sitting on the relevant train tracks have probabilities of death instead of certainty of death.
But other than that. Christian’s points explain well why the scientific community (presumably advising politicians) is not interested in challenge trials.
19. October 2020 at 23:21
How about we just say no to authoritarianism? You can’t order people not to leave their houses, and you can’t order them not to take drugs (vaccines). It’s pretty simple really.
20. October 2020 at 03:18
Cartesian,
I am pretty sure these measures enjoyed strong democratic support. Witness how nicely Ardern was re-elected in New Zealand. It’s not that simple: You can never just do what you want without considering others. You’re not going out into the woods. You’re going out into society, and that’s why society usually has a say in whether or not you’re going out. So if it’s authoritarianism… it’s the democratic kind.
20. October 2020 at 06:57
Believe it or not, although I am beginning to wonder why, I always value your opinion.
So you really do not think that a constant number of deaths, within a very narrow range, since May 15th is interesting enough to comment on? I never saw that said before. Or is it “obvious” and unworthy of comment. Or is it “if one has to explain it you are an idiot” —-or “you obviously cannot count”——or “if you actually think that is interesting you are even more stupid than I thought”
It’s a fact —-and I speculate on its meaning. Consistent with “we are arguing about the wrong things”—-as I am not arguing at all—-just presenting another anomaly—to me at least. Now, I could also speculate on its meaninglessness——-but it would just be a speculation too.
But you have never mentioned this——even that it does not matter. I am not looking for confirmation of my cleverness, I actually value your opinion—-
20. October 2020 at 07:20
I think that the game theory/incentive comment recently highlighted by Cowen is the main issue in vaccine timelines right now.
To parahrase: Drug companies have little to no incentive to quickly get a vaccine to market, especially in the highly polarized USA. First, the guaranteed production contracts mean that the companies do not need to be first to market to get their money. Second, since profiting greatly from a vaccine would induce a great deal of criticism, companies would not really be able to make a lot of money even if they were first or best to market (and there is a lot of competition for these prizes). Third, while companies stand to gain little financially from a successful vaccine, they stand to lose a lot reputationally from a vaccine perceived as rushed that turns out to have some problems in efficacy/side effects. Couple all of this with the FDA’s incompetence/intransigence/desire to avoid the appearance of Trump interference, and you get a horribly delayed US approval/trial process relative to UK/Japan/etc. We have several very likely vaccine candidates, at least one of which should pass trial within a month or two, at least in several other rich, fully developed, cautious economies. Hopefully, the US rollout will not be delayed by the slow US trial process.
20. October 2020 at 09:20
Cartesian, I agree. Fortunately, in Orange County people were never ordered not to leave their houses.
And I’d let people take whatever drugs they choose.
Derek, Our absurdly strict liability regime will cost us many lives.
20. October 2020 at 10:11
Thanks for your response—–no response is very clear!
20. October 2020 at 10:25
Michael, When you write comments in a totally convoluted and incomprehensible manner, I generally believe the most polite choice is to not respond. What do you think?
20. October 2020 at 15:49
mbka,
Sorry but the cat’s out of the bag here. Covid is no worse than the 1957 and 1968 pandemics. Remember those? Didn’t think so. the IFR was higher. Today, we have magical machines that can print out vaccines in a matter of a few hours. These vaccines are probably safe and probably effective. Given the risk level of Covid, it’s definitely not worth risking the vaccine if you’re young and healthy, especially with mRNA vaccines which are known to have lead to auto-immune problems in animal trials. If you’re old, it’s almost certainly worth it after basic safety is established. And those brave souls who want to charge ahead with unproven treatments–God bless their hearts.
But alas, we have failed on every single level. The medical dictatorship pre-determined very early that the only way forward was going to be through lockdowns + vaccines. This meant very little funding for therapeutics and zero funding for retrofitting existing therapeutics. So TDWSHNBN (The Drug Which Shall Not Be Named) was suppressed, along with others. The latest meta study shows P=0.000000049. Yes meta studies are often garbage, but this stuff is pretty straightforward. Similarly, a large British study showed vitamin D may reduce deaths by up to 50%. Do we rush to further study this claim? Do we advise everyone to take vitamin D while we verify it? Of course not. Just “hunker down”–as the man says–and wait for the great ones to deliver us an almighty vaccine.
This is but one slice of the complete and total failure. There were 30+ different testing kits available to us in January. We blocked all but two of them, and we still can’t test effectively. It’s a joke. Only an incompetent dictatorship can fail this badly. And yet we’re in a world where Fauci is praised. Nevermind the NIAID funding for HIV/AIDS by 38% in 2020 to 58% of the entire budget. It’s very clear–today’s dictators are driven by legacy. It’s a damn shame to see so many of our leaders wasting the podium.
In a saner world, those among us who are concerned are more than welcome to purchase a full-face micro-climate and the latest in disinfectant technology. Hell, we’ll subsidize it. Better yet, we’ll actually do science to prove they work. This is guaranteed to be far more effective than whatever mask mandate, because of course we still have ZERO RCTs on mask wearing. The data from Finland, Norway, Holland, Sweeden, etc. is quite clear. And the one and only mask RCT that’s been done? Oh, it’s being held up from publication. Again, lockdown and wait for the vaccine.
People have a right to share the air. We can do a lot to help those in danger, but for those among us who have been walking the earth for 80 damn years, for Christ’s sake let grandma play her bridge! And if misfortune befalls them and the virus turns bad, let them shut the lights off painlessly.
Covid is simply the nail in the coffin of humanities future. We have failed.
20. October 2020 at 16:40
Cartesian, You said:
“Covid is no worse than the 1957 and 1968 pandemics. Remember those?”
It’s just the flu? LOL, I stopped reading right there.
20. October 2020 at 17:03
Cartesian,
2 things – standards for acceptable losses have changed, and most importantly, the result you see is what you get with measures in place. Without any measures in place, things would be worse. What you see is already the attenuated result, not a free roaming pandemic. On another note, your view is very US-centric. All over the world, governments have enacted some kinds of restrictions to movement and business. Countries big and small, democratic or authoritarian, of liberal or tribal traditions. So if there was a dictatorship, it was done in worldwide collusion, Illuminati style. Well, maybe you believe that too.
But see, people worldwide have mostly accepted these measures because everyone understands this to be temporary and for the greater good. People actually enjoy doing the right thing for the greater good. So I think your pessimism is a bit overblown.
20. October 2020 at 20:02
Ssummer,
“No worse” was a wrongly phrased. Not worse in terms of estimated IFR if you correct for demographic change. Way to engage with your readers there.
Mbka,
I enjoy working for the greater good also. There are many ways to do that. Restaurants can start using uv disinfection techniques and study how they work. Do AI-driven, post-hoc cluster busting reseach on camera data in Walmart’s and Starbucks. We can produce highly effective micro-climate helmates. We can do good research on therapeutics, keep people up to date with the best dietary recommendations, and of course work on vaccines. I’m just saying I’m very against authoritarian measures for a virus like this. We seem to have become totally lazy and apathetic.
20. October 2020 at 21:23
meanwhile 10,000 scientists have signed the Great Barrington Declaration.
But surely and economist such as yourself, with zero background in the hard sciences (the real sciences), knows more than these great scientists????
social scientists are some of the dumbest people I know. The stuff that you write – it boggles the mind. I’d laugh, if people were not suffering from your policy ideas – but THEY ARE!
21. October 2020 at 10:26
Cartesian, Covid is far more deadly than the flu, don’t be silly. Without social distancing we’d have a million dead, vs. 60,000 in 1968.
Sorry, but I see no reason to waste time with these silly flu comparisons.
Xu, Finally we agree! Let’s go with the opinion of the majority of scientists on scientific question.
Two problems. Government policies are not a scientific question, and the majority of scientists disagree with you (and Great Barrington) in any case.
BTW, I’ve never advocated lockdowns.
21. October 2020 at 13:37
Scott,
Flue comparisons wasn’t my primary point. I favor taking strong actions. My points were
(1) Immediate voluntary vaccine trials were obviously the right thing to do.
(2) Therapeutics could have saved over 100,000 lives. Latest studies show HCQ helps with P=0.000000049. Vitamin D could cut deaths in half. We’re not rushing to further study these. Not to mention cocktails. Public officials barely recognize these.
(3) Fauci deserves a lot of scorn. He continues to overwhelmingly fund AIDS/HIV, even increasing relative funding in 2020. He wants a cure before he retires.
(4) We’re not researching face coverings scientifically. Should be recommending/researching/subsidizing micro-climate helmets for those concerned/at risk. Ditto for high-tech disinfection.
(5) First RCT on mask wearing is not being published (probably showed a negative result). Also data from Finland, Holland, Norway, Sweeden, etc. show masks are not a keystone variable.
(3) We’re not scientific about disinfection. We should have UV disinfection in restaurants. We’re not even doing research here.
(4) Let grandma play her bridge.
The obsession with masks as the problem without doing good research is just looney. Seriously small potatoes compared to testing, cluster busting, therapeutics, disinfection–all of which we failed at completely and utterly.
21. October 2020 at 13:44
Incidentally, yes for young healthy people the virus is comparable to the flu. We’re spending trillions and trillions of dollars and suffering massive loss in quality of life for something that isn’t a significant risk to us.