You may be surprised to learn that of the trio of long-awaited coronavirus vaccines, the most promising, Moderna’s mRNA-1273, which reported a 94.5 percent efficacy rate on November 16, had been designed by January 13. This was just two days after the genetic sequence had been made public in an act of scientific and humanitarian generosity that resulted in China’s Yong-Zhen Zhang’s being temporarily forced out of his lab. In Massachusetts, the Moderna vaccine design took all of one weekend. It was completed before China had even acknowledged that the disease could be transmitted from human to human, more than a week before the first confirmed coronavirus case in the United States. By the time the first American death was announced a month later, the vaccine had already been manufactured and shipped to the National Institutes of Health for the beginning of its Phase I clinical trial. This is — as the country and the world are rightly celebrating — the fastest timeline of development in the history of vaccines. It also means that for the entire span of the pandemic in this country, which has already killed more than 250,000 Americans, we had the tools we needed to prevent it.
This is from David Wallace-Wells, “We Had the Vaccine the Whole Time,” New York, December 7, 2020.
HT to my Hoover colleague John Cochrane, who hits home run after home run, but this one went out of the park.
If you do nothing else today, read his post.
Wallace-Wells writes:
To be clear, I don’t want to suggest that Moderna should have been allowed to roll out its vaccine in February or even in May.
To be clear, I want not only to suggest that but to advocate that.
John Cochrane explains why:
Even under operation Warp Speed — a truly commendable accomplishment of the Trump Administration that, maybe a year or so from now the TDS crowd might acknowledge — the only thing we have been waiting for is FDA certification: Randomized clinical trials to prove safety and efficacy, before anyone is allowed to take the vaccine.
What’s the free-market way? A drug company can sell a vaccine on January 14, and you can buy it, without fear of going to jail.
Sure, there is an FDA, and a Federal Trade Commission which monitors drug labeling. The vaccine has to say “this is totally untested, and has not been proven safe or effective in clinical trials” and offer a stack of paper about known risks. You sign a stack of consent forms. If you take it, you’re enrolled in our big national database — you just volunteered for the national non-random clinical trial. (We don’t collect much data on drugs that are out there). The FDA rapidly collects information. At the same time, randomized clinical trials are going on. Drugs can give more and more hopeful labels as the results roll in. At some point after Phase III and FDA review, a drug can get the official FDA seal of approval. No, insurance and medicare don’t pay for non-approved stuff. This is free-market nirvana, you pay for unapproved medicines if you want them (see part 1). There is an FTC and a tort system. Drug companies that sell things they know are unsafe or ineffective pay billions.
Sunk costs are sunk, of course. But wouldn’t it be great if we took some learning from this so that we could be more prepared for the next pandemic and not shut down the economy and lose lives both from the pandemic and from the shutdown?
READER COMMENTS
Scott Sumner
Dec 8 2020 at 2:10pm
Good post, but just one quibble:
“A drug company can sell a vaccine on January 14, and you can buy it, without fear of going to jail.”
The vaccine would not have been available in January even without any restrictions, as it takes a long time to manufacture a vaccine even after it is developed. I believe it took them about a month to produce even a small quantity for the NIH.
But yes, we could have had this much sooner, saving tens of thousands of lives, and helping the economy as well.
David Henderson
Dec 8 2020 at 3:45pm
Thanks, Scott.
Yes, I noticed that, which is why I titled my post the way I did.
Thomas Hutcheson
Dec 8 2020 at 2:45pm
Without approaching Libertarian Nirvana, we could have had human challenge trials which, because the do not have to have so many volunteers, can give results much more rapidly.
David Henderson
Dec 8 2020 at 3:45pm
Good point.
Alan Goldhammer
Dec 9 2020 at 9:26am
Not really. You would only have data on those accepted in to the HCT which was a restrictive age group comprised of health young people. You would not have any data on dosing needed for the elderly who usually require either a higher antigen dose or a booster from an adjuvant because their immune systems are not as robust. You also cannot extrapolate any of this data to children which is why companies are doing small follow up trials on that age group.
HCTs won’t give you much information about safety at all as the numbers projected from proponents of this approach are too small to reliably detect significant adverse reactions. Right now it appears that the mRNA vaccines are no different from any other vaccine regarding side effects and in some cases may be slightly safer (we won’t know this until the vaccines are used on large numbers of people).
J Mann
Dec 9 2020 at 11:13am
Even if we could only have gotten HCTs for healthy young people, wouldn’t it have been a good thing to have the virus available for healthy young people by Spring 2000?
1) It would have moved us closer to herd immunity, magnifying the effects of social distancing.
2) You could have vaccinated staff working in nursing homes and other high risk points.
3) It would have made clearing some of the other supply constraints easier once the vaccine was approved for other age groups.
Justin
Dec 8 2020 at 3:28pm
I wonder how Moderna would have operated in a free market though. Collectively we’d benefit if Moderna decides to sell the vaccine right away, but Moderna has its own reputation to worry about and the vaccine could be dangerous. Probably they do some rigorous testing on their own in the absence of regulation. I’m sure they get it out much quicker without the FDA involved, but I wonder how much quicker.
Also, other countries like Russia and China have approved vaccines. Were Moderna and Pfizer unable to sell the vaccines in other countries with lax regulations? The fact that they didn’t makes me somewhat suspicious.
Mark Z
Dec 9 2020 at 1:23am
Did Russia or China offer approval more generously across the board or did they just specifically approve their own sponsored vaccines?
Alan Goldhammer
Dec 9 2020 at 9:19am
to my knowledge the Chinese regulatory authorities have not given a full approval to any of the vaccines being developed there. I don’t know the status of the Russian vaccine.
Gordon
Dec 8 2020 at 6:27pm
One of the things covered by the basics of economics is the marginal cost of increasing production of any sort of good. What specifically was required by Moderna and Pfizer to scale up to production of hundreds of millions of doses? I’d love to hear from a biochemist on what’s needed to produce mRNA on an industrial scale or what’s involved in producing the nanolipid that encapsulates the mRNA. I’m assuming that a company which needs to produce mRNA on a mass scale can’t simply phone up an equipment supplier to meet their capital equipment needs given how relatively new this technology is.
Alan Goldhammer
Dec 9 2020 at 9:18am
It is always humorous when people write about things they have no knowledge about. I don’t write about economics because I am not an economist nor do I pretend to be one. Similarly, economists should not write about drug/vaccine development as they have no clue all that is involved. The big issue with the mRNA vaccines is that this is the first time they have been given to humans. They didn’t even have animal data for SARS-CoV-2 back in the spring because those models were not available until May/June at the earliest (golden hamsters and a couple of different monkeys) so there was only intuition that the vaccine would work.
It’s also not like this vaccine was unknown and arose sui generis in response to COVID-19. In fact, Moderna had done some lab R&D for a proposed Zika vaccine three or so years ago. When Zika disappeared as a public health threat that and other vaccine research stopped (it might have been nice had some safety studies been done to look at various issues with this type of vaccine using the Zika construct as a model, but that’s another failure that can be attributed to the research establishment who did not envision a pandemic coming along so soon).
Because so many of the new COVID-19 vaccines are new constructs and first in humans, FDA insisted on two months of safety data. THIS and not the efficacy data is what delayed approval. Now maybe the Libertarians are willing to accept a vaccine with unknown safety but a vaccine company would not. Say the side effect profile was significant, the only way a company brings this to the market with with some type of Federal compensation and liability waiver such as the one we have for childhood vaccines (and that took a lot of work to get it through Congress).
Going forward, things should be a lot different. Recent research has shown that COVID-19 vaccines can be profiled through their antibody response. There was a paper published on this last week on adaptive immunity and I suspect more testing of vaccine recipients will show a positive correlation to protection. This will do far more than any Human Challenge Trial approach to shortening the efficacy studies that are needed. At present, there is no easy way to study vaccine safety other than through large trials.
To Gordon’s point on manufacturing, there are bottlenecks in the production of these new mRNA vaccines (this is true for a lot of vaccines, witness the need for large numbers of eggs for the yearly influenza vaccine as it’s a complex manufacturing and supply chain process). It is not just a question of qualifying all the reagents that are needed for manufacturing but making sure the process can be scaled up without any compromise of potency. mRNA is a fragile biopolymer which is why the cold chain storage is so important (it is still unclear to me why the Pfizer/BioNTech vaccine requires much colder storage than the Moderna vaccine). Each manufacturing lot has to be qualified prior to release for safety, purity and potency which is not an insignificant task. We don’t know the full details of the manufacturing process for the two companies and what their criteria for lot release is. I hope that the large scale manufacturing goes well and that we get these and the other vaccines ASAP. I’ve been around the pharma industry for most of my working career (and before that had a research project on whooping cough at NIH that involved some work with vaccines jointly with FDA). There will be glitches along the way and there will be some manufacturing lots that may be disqualified for release but I expect this to be a very small number.
It’s worth remembering that this vaccine development has shattered the previous record of just over four years for the Merck mumps vaccine.
David Seltzer
Dec 9 2020 at 6:41pm
Alan. “Similarly, economists should not write about drug/vaccine development as they have no clue all that is involved.” All economists? How about economists who have the experience you claim they don’t. John Cochrane has an undergraduate degree in physics from MIT. He also is a well regarded economist. Should he never talk about time dilation or any other subject as it relates to physics?
Ken P
Dec 10 2020 at 10:08pm
The archaic egg platform for flu vaccine production is actually a great example of the way regulation holds back vaccine innovation. The regulatory cost to license a new vaccine keeps competition down and encourages firms to simply swap out strains for the new season and keep the manufacturing methods the same. There’s little competitive pressure to move beyond the 70 year old status quo. Production in eggs often results in adaptation of vaccine flu strains to the egg cells they replicate in, reducing the effectiveness of the vaccine.
J Mann
Dec 9 2020 at 11:16am
One interesting question is why didn’t any country approve faster release or more liberal trials of the vaccines?
Different countries experimented with a variety of options around privacy, travel controls, forced quarantines, masking, herd immunity, etc., but either no one was willing to roll the dice on vaccines or the manufacturers weren’t willing to work with countries who were.
David Henderson
Dec 10 2020 at 5:34pm
You write:
Good question to which I don’t know the answer.
Jaime L. Manzano
Dec 9 2020 at 5:06pm
Covid 19 may questionably double the deaths annually caused by the flu ….250,000 to 500,000. U.S. deaths annually are around 1 percent of the population…about 3.2 million a year. The Covid 19 increase represents 0.7 percent of the total. Note that Covid 19 deaths include deaths of associated illnesses….diabetes, coonary diseases, cancer, compromised immunity systems….deaths primarily caused by Covid 19 are likely fewer, a substantially lower percentage.
The cost to the response to Covid 19 to the nation, in terms of increased public expenses, and lost economic production, is estimated to be between $3 and $5 trillion. The cost of each additional Covid 19 death….250,000…turns out to be about $20 million each. One needs to consider whether the response was worth it…..Recall the quote from Stalin….”one death is a tragedy….a million deaths are a statistic.”
Phil H
Dec 10 2020 at 8:33am
The claim is that if Moderna had been allowed to sell its vaccine on January 13, without testing and approval, that we could have prevented the pandemic…
I don’t think Henderson or Cochrane have done what Tyler Cowen always urges us to do: solve for equilibrium. If companies are allowed to sell drugs without testing for efficacy or safety, what would actually happen is that thousands of companies would sell snake oil. We know this because it already happens – Alex Jones promotes silver colloids as a panacea, and dupes his listeners out of large amounts of money.
The effective vaccines would not be found, because drug testing is actually hard to do. A “market” can’t do it. So there would be zero incentive for anyone to do the hard work and manufacture real vaccines. Result: no vaccines.
Henry
Dec 10 2020 at 2:11pm
Excellent sapient comment
David Henderson
Dec 10 2020 at 5:32pm
You write:
Yes, drug testing is hard to do. But drug companies do it. Are you arguing that without the FDA’s safety (1938) and efficacy (1962) requirements, they wouldn’t test?
Also, it’s even more extreme to argue that without those requirements, they wouldn’t do the hard work of manufacturing. Why do you think that applies to drugs and no other products? If your claims are right, we should observe that zero safe effective drugs were produced and manufactured before 1938. Are you claiming that that’s true? Are you aware that aspirin came well before 1938?
Phil H
Dec 10 2020 at 10:49pm
Yep. I’m certainly claiming that we’ve had many, many more effective drugs, and much, much more good medical science done since those rules were imposed. And that’s obviously, empirically true.
It seems plain that when a rule requires safety and efficacy, companies work hard to follow that rule. When there is no such rule, they make much less effort. The kind of regime that most effectively promotes the development of effective, safe medicines is a regime that rewards effective, safe medicines. This is just basic economic thinking.
Ken P
Dec 11 2020 at 6:48pm
And I claim that have missed many more effective drugs had those rules not been imposed. We invent things in labs and then it takes 20 years to get them improved. Look at how long the development of immunotherapies have been delayed by requiring patients first try chemotherapies that typically wreak havoc on the immune system as a side effect. Instead of advancements, we end up with tiny changes that show barely statistically significant improvements to existing treatments but have a higher probability of approval.
Had a similar approach been applied to computers, we would all be waiting for the Federal Computer Administration to approve the next improvement to the 5 1/4″ floppy disk.
Phil H
Dec 12 2020 at 7:36am
“I claim that have missed many more effective drugs had those rules not been imposed.”
You can claim it, but it’s not true. If it were true, then we should be seeing many more drugs developed in (a) countries other than the USA, and (b) the USA before the adoption of the current regulatory regime.
Neither of those is the case. The USA is the source of most of the world’s medical breakthroughs. And the speed of medical progress has been much faster in the last 50 years than at any time before.
If your claim is that the FDA regime is actively harming medical development, that is an *extraordinary* claim, and would require *extraordinary* evidence.
Jens
Dec 14 2020 at 4:17am
Actually I find this train of thought (“The vaccine development/production/distribution would have gone faster without excessive regulation”) a lot more interesting and plausible (“It can not be scaled” is always weak for fungible goods) than the “The risks are very small (for you) and if it becomes more risk (e.g. through infection), it is someone’s fault who did something wrong (eventually not relevant for you) “- spin. The latter does not really invoke consequences (Or if it does then very indirectly through the consequences of bad or good norms in general and that is difficult).
Comments are closed.