Canada Needs a New Vaccination Strategy
The US vaccination rollout has been deadly slow, inefficient, and chaotic. It has also been one of the best in the world. Canada, for example, is far behind the US on vaccination.
The Canadian deficit is mostly because they don’t have enough vaccine. Canada bought doses but they didn’t invest in capacity and a deal with China fell through. As a result, Canada won’t be getting lots of vaccine until March or April. Operation Warp Speed invested billions in the Modern vaccine and in early purchases of the Pfizer vaccine and thus got first dibs. The Americans are also not allowing vaccine to be exported to Canada. (We could at least give them access to our AstraZeneca factory!).
Regardless of blame, this puts Canada in a precarious situation. Death rates aren’t as high as in the United States but with new variants exploding, Canada is running a big risk. To get Canadians vaccinated more quickly–including my mother–Canada needs to find ways to stretch their vaccine supply–that means First Doses First, half dosing, intradermal delivery and other dose stretching strategies should be considered.
Many other countries are in a much more worse position than either the United States or Canada.
The Rot is Deep
It’s not just the FDA, or the CDC, or Trump. The rot is deep.
Defense News: Imagine that, for years, the U.S. intelligence community warns about a specific national security threat that could come to pass. One day, it finally does. International observers sound the alarm. The press picks up the scent. Within two weeks, the threat breaches U.S. defenses, and two weeks after that, Americans begin to die. But it takes six months for the U.S. Army to agree to fill the capability gap with a counter-weapon of its own design, and more than a year after the first American casualties, the Army rolls it out.
This, in fact, just happened. It’s the timeline of the Army’s response to the COVID-19 pandemic, an unambiguous threat to life and livelihoods.
It took a full year for the service to design, approve and distribute a face mask — called a Combat Cloth Face Covering, or CCFC — for its soldiers, an effort that required an additional $43.5 million in contracts to provide temporary solutions. That comes out to about $45 per mask, if you assume every active-duty, National Guard and Reserve soldier received one. A pack of 20 N95 masks at Home Depot costs about $20.
And yet, the Army congratulated itself on the “expedited” timeline, compared to the 18- to 24-month procurement cycle such an effort would normally take.
“The system worked as designed,” tweeted a former Marine.
And that is precisely the problem.
One Shot if You Have Been Infected
Here’s noted microbiologist Florian Krammer:
This is now the third paper to find a very very good immune response after one shot of mRNA vaccine in people who had a previous SARS-CoV-2 infection. Time to discuss policy changes, @DrNancyM_CDC@CDCDirector
Paper here.
In other words, as I wrote earlier, “for the 25 million to 100 million Americans who have already been infected by COVID it may be better for them personally to delay the second dose….[thus] a significant fraction of second doses have little to no value.”
It’s good that people like Krammer are signaling that it’s time for policy change. Still, I am frustrated. None of this is unexpected or surprising. It’s just that some people (n.b. I am not referring to Krammer in particular) do not have the training or the mindset to make cost-benefit decisions under uncertainty. That’s ok in ordinary times but during a war, pandemic or takeover fight it’s deadly.
Decentralized Finance and Innovation
Decentralized finance to date seems mostly to be about speculatively trading one cryptocurrency for another. I see little real investment. But in my post on Elrond, I also wrote, “The DeX’s or decentralized exchanges have shown that automated market makers can perform the services of market order books used by the traditional exchanges like the NYSE at lower cost while being easily accessible from anywhere in the world and operating 24/7/365. Thus, every exchange in the world is vulnerable to a DeX.”
One of the reasons that I think DeFi has a big future is that there is much more innovation in the space than in traditional finance. Decentralization is really not a big deal for consumers–it’s even a negative in some respects–but it’s a huge factor for producing innovation.
As an illustration the excellent Bartley Madden (note my biases!) has an interesting idea for reformulating order books on size rather than time.
- One patented concept is that at a specified limit price, priority is based, not on the time when the order was received, but on order size, which incentivizes placing larger orders.
- Additional issued patent claims concern variable prices on limit orders depending on the number of shares traded and other technical details for new ways to facilitate the matching of institutional orders with large retail orders.
- The reason this platform would actually build liquidity is because of the preference given to the largest orders. In operation, a slight price advantage is achieved by the larger investors while the counterparty smaller investors achieve a very quick fill of their entire order.
Or consider the Budish, Crampton, Shim idea for batch auctions to avoid resource waste (rent-seeking) from high-frequency trading. Are these good ideas? I don’t know. But what I do know is that there is little chance that either will be adopted by a major exchange–the transactions costs, including bureaucracy, fear and complacency (why rock the boat?) make it very difficult to innovate. But these ideas could be implemented very quickly by a DeX.
DeFi illustrates “the perennial gale of creative destruction,” and right now we are in the creative phase. New ideas about how to exchange assets are being rapidly deployed and destroyed but a few will prove robust and then watch out. The destruction phase has yet to be begin. Wall Street is unprepared for the onslaught.
Addendum: See also Tyler’s post Will the Future be Decentralized?
Larry Summers, Right Again
No surprise but in can case you were wondering, retail investors trade mostly on noise. A little bit more surprising is that the effect is to make markets less liquid since some models suggest that noise traders make markets more liquid and accurate by bringing in the sharks.
Contrasting with recent evidence that retail traders are informed, we find that Robinhood ownership changes are unrelated with future returns, suggesting that zero-commission investors behave as noise traders. We exploit Robinhood platform outages to identify the causal effects of commission-free traders on financial markets. Exogenous negative shocks to Robinhood participation are associated with increased market liquidity and lower return volatility among stocks favored by Robinhood investors, as proxied by WallStreetBets mentions. Platform outages are also associated with reduced high frequency trader (HFT) activity, indicative of payments for order flow. However, outages have the strongest effect on stocks neglected by HFTs, suggesting that zero–commission traders have direct negative effects on market quality.
Live and Work in Croatia With a Digital Nomad Visa
EuroNews: On January 1st, Croatia became one of a small handful of European countries welcoming digital nomads through the introduction of a long-stay visa. New legislation covering the residence of this category of foreign remote workers was introduced in December 2020 as part of reforms to the foreigners’ law….Under the terms, they are not allowed to provide services to Croatian businesses and are not subject to income tax.
I could work in Dubrovnik for 6 months. Details on how to apply here.
How to Double the Number of Moderna and Pfizer Factories
Theory and data both suggest that a much smaller dose–perhaps as low as 1/4 the current dose—of both the Moderna and Pfizer vaccines are as effective as a larger dose. Half doses of Moderna and Pfizer would be equivalent to instantly doubling the number of Moderna and Pfizer factories and would save hundreds of thousands of lives and be worth hundreds of billions of dollars in world GDP. Clinical data from adults 18-55 from the Moderna Phase II trial already suggest that quarter-doses are effective, which is why Operation Warp Speed chief, Moncef Slaoui has advocated for half-doses (leaving plenty of margin).
“We know that, for the Moderna vaccine, giving half of the dose to people between the ages of 18 and 55, two doses [at] half the dose … we know it induces identical immune response” to the currently authorized dose, Slaoui added.
Another way of putting this is that new clinical trials on dosing would be tremendously valuable. Ideally, we could use correlates of protection and do a bridging trial to infer the effectiveness of half-doses. The FDA has already said they will accept a bridging trial for new mRNA vaccines for variants, which is the right decision. The FDA should also accept a bridging trial for new dosing.
If new clinical trials are deemed necessary, dosing trials could be run as challenge trials but instead of comparing half-doses to placebo we would compare full-doses to half-doses. Thus, everyone in the challenge trial would be vaccinated, massively lowering risks. If we can’t do challenge trials even with vaccinated volunteers (!) then let’s get started on clinical trials. The NIH created the ACTIV program to speed clinical trials. Use it.
New clinical trials are valuable not just for dosing but also for approving new vaccines. Equivalence trials on the Sputnik and Sinopharm vaccines, for example, could be very valuable. In other words, we would trial Sputnik and Sinopharm against Pfizer and Moderna. A lot of people would be quite willing to join a trial in which the worst outcome is most likely getting a somewhat less effective vaccine–that’s much better than no vaccine!
The value of experiments, or let’s call them pilot studies, right now is immense. We can do pilot studies on half dosing for Moderna and Pfizer vaccines much faster and cheaper than we can build twice as many factories. So let’s do it!
Emmott Interviews Tabarrok for the Browser
Bill Emmott, former editor-in-chief of The Economist and now co-director of the Global Commission for Post-Pandemic Policy, talks to Alex Tabarrok, Professor of Economics at George Mason University and co-author of the blog Marginal Revolution, on lessons learned from the pandemic so far, and what lies ahead.
Self-recommending. I’d say it’s a very good interview but there was no question that I was outclassed by Bill Emmott’s zoom background, live from Dublin. Many thanks to the ever-excellent The Browser for hosting.
First Doses First, Now! – New Information
A lot of new information has dropped recently about the efficacy of First Doses First.
First, as I mentioned yesterday, we now have epidemiologists and vaccine researchers saying that for people previously infected with COVID a second dose is not necessary and may be “overkill.” Given how many people have had COVID, this increases the net benefit to First Doses First for everyone significantly.
Second, an important new study verifies that for the AZ vaccine a longer delay for the second dose is better because it generates a more powerful immune response (picture from the FT). This 
is a common finding for vaccines. The authors write:
ChAdOx1 nCoV-19 vaccination programmes aimed at vaccinating a large proportion of the population with a single dose, with a second dose given after a 3 month period is an effective strategy for reducing disease, and may be the optimal for rollout of a pandemic vaccine when supplies are limited in the short term.
In addition “Analyses of PCR positive swabs in UK population suggests vaccine may have substantial effect on transmission of the virus with 67% reduction in positive swabs among those vaccinated.” In other words, the vaccine cuts transmission risk.
As I have said before “the US failure to authorize the AstraZeneca vaccine in the midst of a pandemic when thousands are dying daily and a factory in Baltimore is warmed up and ready to run is a tragedy and dereliction of duty of epic proportions.”
Third, the New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG), a scientific advisory group to the British government, recently considered the risks of immune escape from the delayed second dose strategy and concluded that although the risk is real it is likely small, especially in comparison to other sources of immune escape such as therapeutics and natural infection. Moreover, the risk is outweighed by the measurable benefits of getting more does out quickly.
It is not currently possible to quantify the probability of emergence of vaccine resistance as a result of the delayed second dose, but it is likely to be small.The UK currently has more than 1,000 COVID-19 related deaths each day and has limited supplies of vaccine. In the current UK circumstances the unquantifiable but likely small probability of the delayed second dose generating a vaccine escape mutant must be weighed against the measurable benefits of doubling the speed with which the most vulnerable can be given vaccine-induced protection.
..a single dose of vaccine does not generate a new/novel risk. Given what we have observed recently with the variants B.1.1.7 and B1.351, it is a realistic possibility that over time immune escape variants will emerge, most likely driven by increasing population immunity following natural infection.
Fourth, the British health establishment has largely solidified around First Doses First. Consider this from the Four UK’s Chief Medical Officers.
The 4 UK Chief Medical Officers agree with the JCVI that at this stage of the pandemic prioritising the first doses of vaccine for as many people as possible on the priority list will protect the greatest number of at risk people overall in the shortest possible time and will have the greatest impact on reducing mortality, severe disease and hospitalisations and in protecting the NHS and equivalent health services.
Fifth, the US public health experts are beginning to come around to the economic point of view. Consider Experts tout delaying 2nd COVID vaccine dose as US deaths mount which notes:
“The maximum public health benefit would come from giving a single dose to as many people as possible, and following up with a second dose when supply improves,” said Neal Halsey, MD, of Johns Hopkins University, in an interview. Halsey and Stanley Plotkin, MD, co-authored a letter in Clinical Infectious Diseases last week explaining how delaying a second dose of vaccine would accelerate the US vaccine rollout.
Halsey said data from both companies show the first dose of the vaccine offers significant protection against COVID-19 in the short term, for at least 1 to 3 months after injection. He also said he and Plotkin believe this was the most beneficial public health strategy even before the arrival of new variants of the virus was discovered.
“There are a number of examples of changing [vaccination] course because ACIP takes into account public health impact,” Halsey said. “We asked the ACIP to review in depth this strategy to give one dose as rapidly as possible. Such a meeting should be scheduled as soon as possible.”
The University of Minnesota’s Michael Osterholm, PhD, MPH, said yesterday on “Meet the Press” that he believes the United States has to change direction on vaccine strategy in light of the possibility of a surge of new infections coming from variant strains.
I believe that the US will go to First Doses First. The only question is will we go to First Doses First soon, when it can still help, or will we be forced to do it later in an act of desperation and agony.
Had Covid? You May Need Only One Dose
The barriers are breaking. Step by step we move closer to First Doses First. New results from a small-scale study suggest that people who have had COVID have strong reactions to the first dose and may not need the second dose.
NYTimes: Based on these results, the researchers say, people who have had Covid-19 may need only one shot.
“I think one vaccination should be sufficient,” said Florian Krammer, a virologist at the Icahn School of Medicine at Mount Sinai and an author on the study. “This would also spare individuals from unnecessary pain when getting the second dose and it would free up additional vaccine doses.”
…People who have had Covid seem to be “reacting to the first dose as if it was a second dose,” said Akiko Iwasaki, an immunologist at the Yale School of Medicine. So one dose is probably “more than enough,” she said.
A study published earlier this month reported that surviving a natural infection provided 83 percent protection from getting infected again over the course of five months. “Giving two doses on top of that appears to be maybe overkill,” she added.
So for the 25 million to 100 million Americans who have already been infected by COVID it may be better for them personally to delay the second dose. In short, a significant fraction of second doses have little to no value. This (unsurprising) finding means that First Doses First is an even better strategy even if we can’t condition doses on previous infection.
Most important, First Doses First gets more people significant immunity faster which is good for the vaccinated and also drives down R which is good for society as a whole, even the unvaccinated.
The Biden administration has been more pro-active than the Trump administration on tests and vaccination and has already made some goods calls on getting more doses out faster. I hope they continue to be bold. We need quick, bold, and decisive action.
Just A Few Weeks Delay
NYTimes: Federal regulators could decide within a few weeks whether to allow Moderna, the Massachusetts biotech company that developed one of the two federally authorized Covid-19 vaccines, to increase the number of doses in its vials — which could accelerate the nation’s vaccination rate.
Moderna is hoping to raise the number of doses in its vials to as many as 15 from the current 10 doses, a potential 50 percent increase. The proposal reflects the fact that the company has been ramping up production of its vaccine to the point where the final manufacturing stage, when it is bottled, capped and labeled, has emerged as a roadblock to expanding its distribution.
The FDA will decide in a few weeks???! That is not quick, bold, and decisive action.
Thousands of people have already died over a few weeks delay–multiple times. It’s true that there are tradeoffs but the FDA has no special knowledge or ability to navigate those tradeoffs. Let Moderna make the decision in consultation with vaccinators on the front lines.
The Experts are Very Worried
Here is an interview with Dr. Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine and the lead developer of a COVID vaccine being produced in India. He thinks the AstraZeneca vaccine should be approved immediately, as I have long argued.
President Biden himself announced Tuesday that we’re going to have maybe enough additional doses of the mRNA vaccines to fully vaccinate 300 million Americans by the end of summer or fall.
I’m saying, “Well, no, that’s that’s not gonna work.” Telling us “by the fall” is like telling us “when the glaciers are gonna come back down from Quebec.” I mean, that’s not adequate.
We’re going to have to figure out a way to vaccinate the American people by late spring. That’s a tall order. To beat back the virus we need to give two doses to three-quarters of the population, to 246 million Americans. That’s half a billion immunizations. To get there, we’d need a rate of immunizations two or three times higher than what’s proposed.
….We need vaccinations now.
..things have been slowed down with the AstraZeneca-Oxford adenovirus vaccine. My understanding is that the FDA insisted that they conduct a full-scale Phase Three trial in the U.S., and we won’t have results for that until April. Meanwhile, the European Medicines Agency, the EMA, is going to make a ruling on the AstraZeneca Oxford vaccine on Friday based on studies done in Europe and also probably on data from Brazil and South Africa. [The EMA authorized, AT].
Those are large, reliable studies?
Yeah….Because of these new variants, there’s great urgency here in the U.S. So I’m saying that sometimes we have to do things that take us out of our comfort zone in order to save lives. That means, rather than focusing only on the new study that we’re doing in the U.S., we also look at the dossier presented to the EMA.
As a regulatory agency the EMA is up there with our U.S. FDA. They’re the two best regulatory agencies in the world. So if they sign off, I think we should say, “Look, let’s do it. Let’s use that vaccine.”
We’ve already bought 300 million doses of the AstraZeneca-Oxford vaccine. We’ve paid for it — over a billion dollars — so let’s use it.
…And there’s also the recombinant protein vaccine our lab has developed at Baylor College of Medicine and Texas Children’s Hospital. In India they’re scaling that up to a billion doses. Nobody from the White House has approached us to say, “Hey, Peter, what can we do to bring that vaccine in.”
There seem to be blinders: All they can see is getting the mRNA vaccines. I don’t quite know what’s driving that. We have to figure out a way to bring the other ones on board.
And soon! We’re in the eye of the hurricane.
Hat tip: Jim Ward.
What I Have Been Reading (Alex)
The Economics of Small Things–An Indian economist in the United States offers a sweet and gentle introduction to economics drawn from his personal and professional life. I enjoyed many of the essays though I have to disagree with one–it makes a difference whether you go to the mangoes or the mangoes come to you as Tyler and I showed!
Wretched Refuse?: The Political Economy of Immigration and Institutions–Kudos to Nowrasteh and Powell for doing the work that critics of immigration have never done–that is, actually test for the effect of immigration on culture and cohesion. I can do no better than quote The Economist, “Wretched Refuse?” is… full of charts and regression analysis. It is also highly original, and takes a chainsaw to the most intellectually respectable case against immigration. No serious economist denies that when people move from poor countries to rich ones, they become more productive and their wages soar. It seems likely, therefore, that more migration would make the world much richer. However, some scholars think that too large an influx from, say, Congo to Canada would make Canada more like Congo—ie, the immigrants would import Congolese habits, and gradually make Canadian institutions more like the corrupt and lawless ones that keep Congo poor. Yet remarkably little effort has been made to test this hypothesis. Messrs Nowrasteh and Powell do so as rigorously as they can.”
The Infinite Machine–I was disappointed in this history of Ethereum. It doesn’t try to explain any of the technical details of Ethereum which is ok but it also doesn’t go into great detail on the personalities, leaving one with a journalistic history of what happened with some short glosses on the people.
The Splendid and the Vile: A Saga of Churchill, Family, and Defiance During the Blitz–As the bombs fall on London, Churchill struggles to increase the production of aircraft, to diplomatically bring the United States into the war, to hold his government together even as British forces are defeated abroad. Meanwhile his teenage daughter falls in love, his son deals with a gambling problem and divorce and his aide looks for a wife. The Splendid and the Vile is a tremendous story of Churchill’s first year in office based on meticulous research and told at a thrilling, breakneck pace. A great read at any time. A poignant and apt read now.
Causal Inference: The Mixtape–an excellent introduction to causal inference. The Mixtape marks the beginning of the DAG era in econometrics.
The EU Failed the World’s Easiest Cost-Benefit Test
From early on in the crisis I was telling governments, “this is the world’s easiest cost-benefit test” because:
The EU response:
However, the EU approach came with strings. The commission, negotiating for the first time on vital medicines, felt that EU countries would demand value for money, so it dragged out the talks to secure better prices and product liability guarantees. That meant it signed the contracts with AstraZeneca in August, three months after the UK’s contract.
Hat tip: Arthur Baker.
Addendum: On the plus side the EU has authorized the AstraZeneca vaccine. The United States should immediately do the same. Get the Baltimore factory running.
Scott Sumner on Vaccine Nationalism
EconLib: Experts in the UK have looked at the AstraZenaca vaccine and found it to be safe and effective. And yet Americans are still not allowed to use the product. So if paternalism is not the actual motive, why do progressives insist that Americans must not be allowed to buy products not approved by the FDA? What is the actual motive?
The answer is nationalism. The experts who studied the AstraZenaca vaccine were not American experts, they were British experts. Can this form of prejudice be justified on scientific grounds? Obviously not. There has been no double blind, controlled study of comparative expert skill at evaluating vaccines. We have no way of knowing whether the UK decision is wiser than the FDA decision. Instead, the legal prohibition is being done on nationalistic grounds. We are told to blindly accept the incompetence of British experts, without any proof. (And even if you believed there was solid evidence that one country’s experts were better than another, it would not explain why each developed countries relies on their own experts. They can’t all be best!)
These debates always end up being like a game of whack-a-mole. Shoot down one argument and regulation proponents will simply put forth another. Their minds are made up. You say people shouldn’t be allowed to take a vaccine unless experts find it to be safe and effective? OK, the UK experts did just that. You say that only the opinion of US experts counts because our experts are clearly the best? Really, where is the scientific study that shows that our experts are the best? I thought you said we needed to “trust the scientists”? Now you are saying we must trust the nationalists?
…what’s wrong with the following three-part system of regulation as a compromise solution:
1. FDA approved drugs can be consumed by anyone in America.
2. Drugs approved by any of the top 20 advanced countries (but not the FDA) can be consumed by anyone willing to sign a consent form indicating that they understand the FDA has not approved this product. I’ll sign for AstraZeneca. (The US government puts together a list of 20 reputable countries.)
3. Drugs approved by none of the top 20 developed economies will still be banned.
This is what regulation would look like if paternalism actually were the motivating factor. But it’s not. It’s Trump-style nationalism that motivates progressives to insist that only FDA approved drugs can be sold in America. They may look down their noses at Trump, but they implicitly share his nationalism.
I agree, of course, and have long supported Pharmaceutical Reciprocity.