Wednesday assorted links

1. How to run a simple and fairly quick clinical trial on First Doses First.  It is funny how you do not hear the critics suggest the merits of further investigation.

2. “American Chess Magazine Releases Their List of the Top 1 Shows of 2020.”  You should not need to click on the link.

3. The redone Joshua Gans calculations (great praise to him for trying to put numbers on everything) now favor a policy of First Doses First.  And another useful model supporting First Doses First.  The silence on the other side of the debate is deafening.

4. Is peer-reviewed work increasingly boring?

5. Making policy for a low-trust world (so far the year’s best short essay).

6. Hail Palau, it might soon have all its people vaccinated.

First Doses First and Herd Immunity

The simplest argument for First Doses First (FDF) is that 2*0.8>.95, i.e. two vaccinated people confers more immunity than one double vaccinated person. But there is more to it than that. Perhaps more important is that with FDF we will lower R more quickly and reach herd immunity sooner. Here’s an extreme but telling example.

Suppose you have a pop of 300 million, need 2/3 to get to herd immunity and you have 100m doses and can vaccinate 100m a month. Then with FDF you vaccinate 100m in first month and a new 100m in the second month and then you are “done.” i.e. you can then do 2nd doses more or less at leisure since you are at herd immunity (yes, I know about overshooting, this is a simple example). If instead you do second doses you vaccinate 100m in first month and the same 100m in the second month which leaves 100 million at risk for another month. Under second doses you don’t reach herd immunity until the third month. Thus, under FDF you save a 100m infection-month which is a big deal.

Now when you put this into a more sophisticated SEIR model you won’t get as strong a result but the result will be in the same direction. Note also that getting to herd immunity sooner is probably the best thing we can do to prevent further mutations.

See also Youyang Go’s thread where he discusses his modeling of similar ideas. He notes:

Reaching herd immunity two or three months sooner will have profound benefits throughout society, ranging from fewer cases & deaths to faster economic recovery.

Addendum: Please read Tyler’s post, FDF?-Show Your Work! before you comment.

“New York’s mass-vaccination plans are shelved as Cuomo takes different path”

County officials who have for years been planning for a mass vaccination said they are seeing that training and preparation — much of it funded by millions of dollars in federal grants — pushed aside as the administration of Gov. Andrew M. Cuomo has retained control of the state’s coronavirus vaccination program, including having hospitals rather than local health departments administer the doses.

Interviews with multiple county officials over the past week confirm that many are unclear why the governor’s administration has not activated the county-by-county system, a plan that included recent practice sessions in which members of the public received regular flu vaccines at drive-thru sites.

…In Albany County, officials have privately said they could vaccinate the population of the southern half of the county in a few days if they were given the coronavirus vaccines and allowed to mobilize their plan.

Here is the full, gory story.  It is clear they have just begun thinking about this.  I really do not understand why Paul Krugman has been praising the New York State response for so many months, they have gone from one disgrace to another.  Ross Barkan offers further commentary.  And here is de Blasio on Cuomo.

As a side note this is interesting: “The Times Union is not disclosing the [vaccination] location because county officials contend the vaccination sites should not be publicly disclosed for security purposes.”

To be clear, other states are messing up too, some of them worse than NY.

John Geanakoplos tells Yale to keep on spending on excellence

Putting things into some perspective, Geanakoplos also said that the $250 million Yale lost as a result of COVID-19 represents one day’s average fluctuation in the value of the endowment. The salary freeze that accompanied the hiring freeze, meanwhile, saved the Faculty of Arts and Sciences $5 million.

And:

Geanakoplos, for instance, said at an October Senate meeting, “I hope the Yale administration will listen to the science of financial crises and take the right calculated risk to deal with the COVID financial crisis.”

Yale, he continued, is “unlikely in the next 50 years to have so good an opportunity to make progress in faculty excellence and diversity as it has right now.” Many peer institutions, especially public ones, continue to face the financial fallout of COVID-19, and so Yale’s “opportunity is now huge,” Geanakoplos urged. “Seize it … Seeing an opportunity while having the money at the same time is truly extraordinary.”

Here is the full story, via Mike.

What should I ask Brian Armstrong?

I will be doing a Conversation with him, in case you do not know Brian is co-founder and CEO at Coinbase.

So what should I ask him?  And to be clear, this is the conversation I want to have with him, namely one that maximizes my selfish learning, not your mood affiliation.  Here is the Wikipedia page for Coinbase, here is Brian on Twitter, why does a major CEO and person with 410k Twitter followers have no Wikipedia page of his own?

The politics of Covid just got even more hellish

That is the title of my latest Bloomberg column, here is one excerpt:

Preliminary data indicate that the new strain in the U.K. allows the virus to spread from one person to another more easily. The practical upshot is that even the strict lockdowns of early 2020, such as the one just ordered in the U.K. by Prime Minister Boris Johnson, may not be enough to reverse the spread of the virus.

It is far from obvious that politicians will be able to sell voters on strict lockdowns if they still allow the virus to spread. Furthermore, vaccine distribution has been sufficiently slow that a full lockdown would have to last for many months, and that probably isn’t feasible or desirable. Yet not having lockdowns would lead to a much more rapid spread of the virus, overloading hospitals and public health facilities.

And:

The biggest moral dilemmas might come in those countries that to date have been fairly successful at containing the spread of the virus. Apart from restrictions on foreign travel, life in Taiwan has been normal for some time now, and Covid-related casualties have been miniscule. Other successful examples of virus containment can be found throughout Asia and the Pacific.

But how will those countries deal with the new strain? It has already appeared in both Taiwan and China. So far it has not taken over, but the previous tactics of quarantine and tracing may no longer suffice, should the new strain become more active. It is already spreading in Denmark, which did a good job against Covid-19 early on.

Imagine being a leader of a country that has successfully contained Covid, and now realizing that a single mistake could undo almost a year of very hard work. You also know that, precisely because your country has been so effective at fighting the virus, it is not on the verge of vaccinating your entire population. What if you let a single returning citizen pass through customs taking one Covid test rather than three? What if you then cannot control the subsequent spread of the strain that person is carrying?

When was the last time that stakes for such apparently minor decisions were so high? How will leaders deal with the extreme moral anxiety that their decisions will likely induce?

It is like we are living in a horror movie, and just when we think it’s over, the monster comes back, stronger than ever.

Important throughout.

The AstraZeneca Factory in Baltimore

Emergent BioSolutions has a factory in Baltimore that operates under an innovative long-term private-partnership agreement with BARDA. Essentially BARDA subsidized the factory in return for an option to use it in an emergency–Operation Warp Speed exercised that option and in June-July AstraZeneca signed a licensing agreement with Emergent for large-scale manufacturing of its vaccine.

According to the Baltimore Sun the AZ vaccine is already being made at the facility. I hope they are making millions of doses. I want the AZ vaccine approved in the United States immediately but if we won’t take it (yet) they can still export it to Britain and the many other countries which will approve the vaccine.

More generally, there are three vaccines in the near term pipeline. AstraZeneca, Johnson and Johnson and Novavax. If there is anything that we can do to speed these vaccines to people it would be worth billions. All of these vaccine manufacturers should be making and storing millions of doses now.

It’s important to understand that a policy like First Doses First works best when capacity is increasing rapidly so approving these additional vaccines is part of an integrated plan.

Here’s the factory in Baltimore. It’s capable of producing tens to hundreds of millions of vaccine doses a year. Isn’t it beautiful?

AstraZeneca’s coronavirus vaccine candidate is being manufactured at Emergent BioSolutions' facility in East Baltimore, shown in a 2017 photo.
The factory is ready to go. Are we?

Addendum: One more thing. Stop telling me that the problem is vaccine distribution not supply. Guess what? I am thinking ahead.

First Doses First? — show your work!

Alex has been arguing for a “First Doses First” policy, and I find his views persuasive (while agreeing that “halfsies” may be better yet, more on that soon).  There are a number of numerical attempts to show the superiority of First Doses First, here is one example of a sketched-out argument, I have linked to a few others in recent days, or see this recent model, or here, here is an NYT survey of the broader debate.  The simplest numerical case for the policy is that 2 x 0.8 > 0.95, noting that if you think complications overturn that comparison please show us how.  (Addendum: here is now one effort by Joshua Gans).

On Twitter I have been asking people to provide comparable back-of-the-envelope calculations against First Doses First.  What is remarkable is that I cannot find a single example of a person who has done so.  Not one expert, and at this point I feel that if it happens it will come from an intelligent layperson.  Nor does the new FDA statement add anything.  As a rational Bayesian, I am (so far) inferring that the numerical, expected value case against First Doses First just isn’t that strong.

Show your work people!

One counter argument is that letting “half-vaccinated” people walk around will induce additional virus mutations.  Florian Kramer raises this issue, as do a number of others.

Maybe, but again I wish to see your expected value calculations.  And in doing these calculations, keep the following points in mind:

a. It is hard to find vaccines where there is a recommendation of “must give the second dose within 21 days” — are there any?

b. The 21-day (or 28-day) interval between doses was chosen to accelerate the completion of the trial, not because it has magical medical properties.

c. Way back when people were thrilled at the idea of Covid vaccines with possible 60% efficacy, few if any painted that scenario as a nightmare of mutations and otherwise giant monster swarms.

d. You get feedback along the way, including from the UK: “If it turns out that immunity wanes quickly with 1 dose, switch policies!”  It is easy enough to apply serological testing to a control group to learn along the way.  Yes I know this means egg on the face for public health types and the regulators.

e. Under the status quo, with basically p = 1 we have seen two mutations — the English and the South African — from currently unvaccinated populations.  Those mutations are here, and they are likely to overwhelm U.S. health care systems within two months.  That not only increases the need for a speedy response, it also indicates the chance of regular mutations from the currently “totally unvaccinated” population is really quite high and the results are really quite dire!  If you are so worried about hypothetical mutations from the “half vaccinated” we do need a numerical, expected value calculation comparing it to something we already know has happened and may happen yet again.  When doing your comparison, the hurdle you will have to clear here is very high.

When you offer your expected value calculation, or when you refuse to, here are a bunch of things you please should not tell me:

f. “There just isn’t any data!”  Do read that excellent thread from Robert Wiblin.  Similar points hold for “you just can’t calculate this.”  A decision to stick with the status quo represents an implicit, non-transparent calculation of sorts, whether you admit it or not.

g. “This would risk public confidence in the vaccine process.”  Question-begging, but even if true tell us how many expected lives you are sacrificing to satisfy that end of maintaining public confidence.  This same point applies to many other rejoinders.  It is fine to cite additional moral values, but then tell us the trade-offs with respect to lives.  Note that egalitarianism also favors First Doses First.

h. “We shouldn’t be arguing about this, we should be getting more vaccines out the door!”  Yes we should be getting more vaccines out the door, but the more we succeed at that, as likely we will, the more important this dosing issue will become.  Please do not try to distract our attention, this one would fail in an undergraduate class in Philosophical Logic.

i. Other fallacies, including “the insiders at the FDA don’t feel comfortable about this.”  Maybe so, but then it ought to be easy enough to sketch for us in numerical terms why their reasons are good ones.

j. All other fallacies and moral failings.  The most evasive of those might be: “This is all the more reason why we need to protect everyone now.”  Well, yes, but still show your work and base your calculations on the level of protection you can  plausibly expect, not on the level of protection you are wishing for.

At the risk of venturing into psychoanalysis, it is hard for me to avoid the feeling that a lot of public health experts are very risk-averse and they are used to hiding behind RCT results to minimize the chance of blame.  They fear committing sins of commission more than committing sins of omission because of their training, they are fairly conformist, they are used to holding entrenched positions of authority, and subconsciously they identify their status and protected positions with good public health outcomes (a correlation usually but not always true), and so they have self-deceived into pursuing their status and security rather than the actual outcomes.  Doing a back of the envelope calculation to support their recommendation against First Doses First would expose that cognitive dissonance and thus it is an uncomfortable activity they shy away from.  Instead, they prefer to dip their toes into the water by citing “a single argument” and running away from a full comparison.

It is downright bizarre to me — and yes scandalous — that a significant percentage of public health experts are not working day and night to produce and circulate such numerical expected value estimates, no matter which side of the debate they may be on.

How many times have I read Twitter threads where public health experts, at around tweet #11, make the cliched call for transparency in decision-making?  If you wish to argue against First Doses First, now it is time to actually provide such transparency.  Show your work people, we will gladly listen and change our minds if your arguments are good ones.

Does soil heterogeneity induce greater individualism?

Itzchak Tzachi Raz says maybe so:

This paper studies the impact of social learning on the formation of close-knit communities. It provides empirical support to the hypothesis, put forth by the historian Fred Shannon in 1945, that local soil heterogeneity limited the ability of American farmers to learn from the experience of their neighbors, and that this contributed to their “traditional individualism.” Consistent with this hypothesis, I establish that historically, U.S. counties with a higher degree of soil heterogeneity displayed weaker communal ties. I provide causal evidence on the formation of this pattern in a Difference-in-Differences framework, documenting a reduction in the strength of farmers’ communal ties following migration to a soil-heterogeneous county, relative to farmers that moved to a soil-homogeneous county. Using the same design, I also show that soil heterogeneity did not affect the social ties of non-farmers. The impact of soil heterogeneity is long-lasting, still affecting culture today. These findings suggest that, while understudied, social learning is an important determinant of culture.

Here is the full paper.  See also his paper on homesteading: “…we find that areas with greater historical exposure to homesteading are poorer and more rural today.”

Monday assorted links

1. Did irrigation entrench the patriarchy?  By Alice Evans.

2. Casey Mulligan measures deaths of despair.

3. “We create a novel reign-level dataset for European monarchs, covering all major European states between the 10th and 18th centuries. We first document a strong positive relationship between rulers’ intellectual capabilities and state-level outcomes…We also show that rulers mattered only where their power was largely unconstrained. In reigns where parliaments checked the power of monarchs, ruler ability no longer affected their state’s performance.”  Link here.  And Ian Bremmer’s Eurasia Group on the top risks for 2021.

4. The Military Health System: “We find evidence that off-base care is associated with slightly greater resource intensity, but also notably better outcomes, suggesting marginal efficiency gains from care privatization.” That’s from Jon Gruber and co-authors, not the Heritage Foundation.

5. “Countries with higher death rates in the war [WWII] saw lower death rates in the first wave of the COVID pandemic, though the effect faded in the pandemic’s second wave.

Half-Doses as Good as Full?

NYTimes: A top official of Operation Warp Speed floated a new idea on Sunday for stretching the limited number of Covid-19 vaccine doses in the United States: Halving the dose of each shot of Moderna’s vaccine to potentially double the number of people who could receive it.

Data from Moderna’s clinical trials demonstrated that people between the ages of 18 and 55 who received two 50-microgram doses showed an “identical immune response” to the standard of two 100-microgram doses, said the official, Dr. Moncef Slaoui.

Dr. Slaoui said that Operation Warp Speed was in discussions with the Food and Drug Administration and the pharmaceutical company Moderna over implementing the half-dose regimen. Moderna did not respond immediately to a request for comment.

Each vaccine would still be delivered in two, on-schedule doses four weeks apart, Dr. Slaoui said in an interview with “CBS’s Face the Nation.” He said it would be up to the F.D.A. to decide whether to move forward with the plan.

Half dosing would double Moderna doses permanently rather than temporarily (as with First Doses First). Thus, I would be very happy to see half-dosing and it would obviate the need for FDF.

I and a handful of others started to discuss and advocate First Doses First on Dec. 8 and many times since then. The advocacy was then joined by Tony Blair and by many epidemiologists, immunologists, vaccine researchers, physicians and public health experts as well, of course, by the British experts on the Joint Committee on Vaccination and Immunisation. It’s clear that the FDA and Operation Warp Speed are now feeling the pressure to take some serious actions to increase supply. If so, my small efforts will have had a very high return.

Keep the pressure on.

Addendum: By the way, the British have yet to approve the Moderna vaccine (probably because they can’t get doses for some time anyway) and the AstraZeneca vaccine appears to work better with a longer dosing interval. So FDF makes sense for the British and we can do half-dosing on Moderna, potentially setting a new and beneficial standard for the entire world.

How will we interpret data on the new strain?

Instead of exploding relative to a baseline of 0 cases (like in March), the new strain will be exploding relative to a baseline of around 200,000 cases per day. As a result, day-to-day random noise will completely mask any increase in infections from the new strain until it becomes dominant — around day 40 in the above chart. This means that if people use the overall numbers to guide their levels of precaution, our reaction time could lag by two or three weeks compared to March — as if we had locked down in early April instead of mid-March.

Now, this isn’t entirely a correct comparison because the rate of exponential growth will be much below 1.36; a reasonable guess might be 1.12. (You can get this by assuming R = 1.6 and assuming a generation time of 4 days.) But the overall point is the same: because any increase in the prevalence of the new strain will be masked by noise in current COVID levels, the new strain won’t be evident in overall numbers until it starts contributing hundreds of thousands of daily infections.

That is from Eric Neyman, good points thought note we will have independent measures of the spread of the new strain, with shorter lags than is currently the case.

Globalization is older than you think

Asian spices such as turmeric and fruits like the banana had already reached the Mediterranean more than 3000 years ago, much earlier than previously thought. A team of researchers has shown that even in the Bronze Age, long-distance trade in food was already connecting distant societies…

Working with an international team to analyze food residues in tooth tartar, the LMU archaeologist has found evidence that people in the Levant were already eating turmeric, bananas and even soy in the Bronze and Early Iron Ages. “Exotic spices, fruits and oils from Asia had thus reached the Mediterranean several centuries, in some cases even millennia, earlier than had been previously thought,” says Stockhammer. “This is the earliest direct evidence to date of turmeric, banana and soy outside of South and East Asia.” It is also direct evidence that as early as the second millennium BCE there was already a flourishing long-distance trade in exotic fruits, spices and oils, which is believed to have connected South Asia and the Levant via Mesopotamia or Egypt.

Here is the full account, I strongly suspect globalization is much older than is commonly believed. Via Bruno M.