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.
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.
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?
Addendum: One more thing. Stop telling me that the problem is vaccine distribution not supply. Guess what? I am thinking ahead.
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.
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.
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.
…researchers have just declared that there was a huge, hidden outbreak in the capital of Sudan. In the absence of a good death registration system, they used a molecular and serological survey and an online one distributed on Facebook, where people reported their symptoms and whether they’d had a test. The researchers calculated that Covid-19 killed 16,000 more people than the 477 deaths confirmed by mid-November in Khartoum, which has a population roughly the size of Wisconsin’s.
Here is the full NYT article by Ruth Maclean. The main theme of the piece is that Africa may not have escaped Covid by nearly as much as we had thought.
Total vaccine doses distributed: 388,100
Total vaccine doses administered: 75,288
Here is the link (which at some point will update), that is below 20 percent.
We need to do much better than this. As a nation, Israel is doing about 10x better than the United States. You might think for some intrinsic reasons Israel could do 2x or 3x better, but 10x? It is time to get our act together.
And here is (very poor) performance for the various German Bundesländer (in German).
The British approved the Pfizer vaccine, they approved the AstraZeneca vaccine, they moved to first doses first and now they are allowing (not yet encouraging they are running a trial) mix and match. Under the present circumstances, the British focus on doing what it takes to save lives is smart, admirable, and impressive.
As I wrote on Dec. 10, in Herd Immunity is Herd Immunity:
Mix and matching has two potentially good properties. First, mix and matching could make the immune system response stronger than either vaccine alone because different vaccines stimulate the immune system in different ways. Second, it could help with distribution. It’s going to be easier to scale up the AZ vaccine than the mRNA vaccines, so if we can use both widely we can get more bang for our shot.
Addendum: The CDC is projecting 80,000 COVID deaths in the United States over the next three weeks.
We are seeing our state governments doing a poor job — yes a very poor job –distributing the vaccine. You can take this as evidence for various theories of bureaucratic dysfunctionality and it is. But still at the end of the day, always ask about the cross-sectional variation!
Virginia runs prisons, schools, maintains roads, has a Medicaid program, and various state-level functions, such as hiring staff for the governor, some of those in conjunction with other levels of government. Maybe those services are not productivity marvels, but they work OK — I’ve lived here for a long time. So why the differences? Here are a few hypotheses, not all of which need be true:
1. Learning curves are steep. Most of what governments do is just terrible at the beginning, but eventually there is learning and improvement. What is different here is simply the hurry.
2. Interest groups make everything run. It is clear who benefits from state-level Medicaid programs, and those constituencies keep the programs on track. In contrast, the beneficiaries from rapid Covid vaccination are quite diffuse and are not represented by strong, exclusive organizations.
3. Too many layers of government (and society) are involved. The states are waiting for the local public health authorities, who are waiting for the counties, who are waiting for the Feds, and so on. The private sector is involved too, through CVS and the like. No one is picking up the ball and running with it. No one was told who moves first. In contrast, the lines of responsbility for running roads, schools, and the like are fairly clear.
4. The real problem is the citizenry. The lines to get these vaccines for the 1A group are not long. Government made one mistake of assuming the first round of take-up would be rapid, but the real problem is the sluggishness of the demanders. And things will be OK once we get past the 1A group and open up distribution more broadly.
5. Logistics mentality is lacking. Our state governments have specialized in Medicaid, while contracting our schools to the localities and road construction and repair to the private sector. There is perhaps not a strong enough core of logistic expertise and logistics culture in most state governments.
What else? And what are the relative weights on the truth of these hypotheses? To what extent can we use these and other hypotheses to explain cross-sectional variation across the states? Why are West Virginia and the Dakotas doing relatively well in vaccine distribution so far, when those are not typically considered the most effective state governments?
Again, always ask about the cross-sectional variation!
I was going to write a long blog post on the new strain but Zeynep Tufekci has written an excellent piece for The Atlantic. I will quote from it and add a few points.
One of the big virtues of mRNA vaccines is that much like switching a bottling plant from Sprite to 7-Up we could tweak the formula and produce a new vaccine using exactly the same manufacturing plants. Moreover, Marks and Hahn at the FDA have said that the FDA would not require new clinical trials for safety and efficacy just smaller, shorter trials for immune response (similarly we don’t do new large-scale clinical trials for every iteration of the flu vaccine.) Thus, if we needed it, we could modify mRNA vaccines (not other types) for a new variant in say 8-12 weeks. As Zeynep notes, however, the vaccines are very likely to work well for the new variant. It’s nice to know, however, that we do have some flexibility.
The real worry is not that the vaccines won’t work but that we won’t get them into arms fast enough. We were already going too slow but in a race against the new more transmissible variant we are looking like tortoises.
A more transmissible variant of COVID-19 is a potential catastrophe in and of itself. If anything, given the stage in the pandemic we are at, a more transmissible variant is in some ways much more dangerous than a more severe variant. That’s because higher transmissibility subjects us to a more contagious virus spreading with exponential growth, whereas the risk from increased severity would have increased in a linear manner, affecting only those infected.
Here’s a key example from epidemiologist Adam Kucharski:
As an example, suppose current R=1.1, infection fatality risk is 0.8%, generation time is 6 days, and 10k people infected (plausible for many European cities recently). So we’d expect 10000 x 1.1^5 x 0.8% = 129 eventual new fatalities after a month of spread. What happens if fatality risk increases by 50%? By above, we’d expect 10000 x 1.1^5 x (0.8% x 1.5) = 193 new fatalities.
Now suppose transmissibility increases by 50%. By above, we’d expect 10000 x (1.1 x 1.5)^5 x 0.8% = 978 eventual new fatalities after a month of spread.
…the key message: an increase in something that grows exponentially (i.e. transmission) can have far more effect than the same proportional increase in something that just scales an outcome (i.e. severity).
I argued that the FDA should have approved the Pfizer vaccine, on a revocable basis, as soon as the data on the safety and efficacy of its vaccine were made available around Nov. 20. But the FDA scheduled it’s meeting of experts for weeks later and didn’t approve until Dec. 11, even as thousands of people were dying daily. We could have been weeks ahead of where we are today. Now the epidemiologists are telling us that weeks are critical. As Zeynep notes holding back second doses looks like a clear mistake and the balance of the evidence also suggests we should move to first doses first:
All this means that the speed of the vaccine rollout is of enormous importance.
…Meanwhile, the United States was reportedly planning to hold back half the vaccine it has in freezers as a hedge against supply-chain issues, and some states may be slowed down by murky prioritization plans. Scott Gottlieb—the former FDA chief and a current board member of Pfizer—has argued that the U.S. should also go ahead with vaccinating as many people as possible right now and trust that the supply chain will be there for the booster. Researchers in Canada—where some provinces decided to vaccinate now as much as possible without holding half in reserve, and will administer the booster with future supplies—estimate that this type of front-loading can help “avert between 34 and 42 per cent more symptomatic coronavirus infections, compared with a strategy of keeping half the shipments in reserve.” (Note that this strategy, which is different from the one the United Kingdom just announced it will adopt in prioritizing the first dose, does not even necessarily involve explicitly changing booster timing protocols in order to maximize vaccination now; it just means not waiting to get shots into arms when the vaccines are currently available.) These were already important conversations to have, but given the threat posed by this new variant, they are even more urgent.
Perhaps most critically, the FDA should approve the AstraZeneca vaccine if not as part of Operation Warp Speed then on a right to try basis. We need every weapon in the arsenal. How many times must we learn not to play with exponential matches?
Addendum: See also this excellent Miles Kimball post, How Perfectionism Has Made the Pandemic Worse.
States and local public health officials have warned for months that they would need more than $8 billion in additional funding to stand up the infrastructure needed to administer vaccines. The Trump administration instead provided states $340 million in funding to prepare for vaccinations. Congressional lawmakers also balked for months at appropriating additional funding for vaccine distribution, although the coronavirus stimulus package signed by President Trump on Sunday included $8 billion in funding for that effort.
That is from a recent StatNews article. Now I gladly would have expanded the federal contribution, by several times over if need be. But people, let us put this in perspective. First, the states got the $8 billion they were asking for. Yes, the delay is very very bad, but let’s say they had come up with $8 billion on their own several months ago.
Total state and local spending is about $3.7 trillion, $2.3 trillion from the states alone. $8 billion is how much of that?
About one-third of one percent.
Our states cannot come up with one third of one percent of their budgets to meet the greatest emergency in my lifetime?
This has been a pandemic of outrages, but this undercovered issue is one of the very largest of those outrages. Heaven forbid that states should have to take a sliver of their budget away from deserving recipients. To so many people this is simply unthinkable, and I mean that word in a very literal sense.
(And yes I do know this year is especially tight on state budgets, etc. But even if those budgets were cut to a third of their normal level — hardly the case — that is still only one percent of state budgets.)
The other outrage is how few people have been willing to criticize the states for not having done better fiscal planning here. You will find many deserved criticisms of Trump on this, but there is more than one line of defense, or at least there is supposed to be. So yes, you should be mad at the states.
Here is the summary:
On this special year-in-review episode, producer Jeff Holmes sat down with Tyler to talk about the most popular — and most underrated — episodes, Tyler’s personal highlight of the year, how well state capacity libertarianism has fared, a new food rule for ordering well during the pandemic, how his production function changed this year, why he got sick of pickles, when he thinks the next face-to-face recording will be, the first thing he’ll do post vaccine, an update on his next book, and more.
Here is the full dialogue, with audio and transcript, here is one short excerpt:
I think the downside of state capacity libertarianism is simply realizing there are some very nice features to not being surveilled all the time, as they do in China. When I said a moment ago that the United States is not very good at trace, though it’s good at innovating — if you had stronger state capacity, presumably you should worry more about state surveillance, and I do. That, to me, is the best case against state capacity libertarianism as I envision it.
Even though having a good trace regime would have been fine in this instance, I’m not sure it would have been a good precedent.
I also tell you what I thought of the guests we had on for the year, and also which episode had the most downloads. Self-recommended.
And if you have enjoyed this year in Conversations, please consider donating here before the end of the year. Thank you!
The UK will move to a “first shot” strategy. The priority will be to give at-risk groups one shot of vaccine, even if it means delaying the second dose. That’s a massive change of strategy.
Here is further information. And here, via Peter Whittaker. C’mon American public health establishment get your act together, I don’t see that very many of you have had the stones to endorse such a change.
On December 12 I wrote:
We should vaccinate 6 million people with first dose NOW. It is deadly cautious to hold second dose in *reserve*. Supply chain will be ok and the exact timing of the second dose is not magical and likely not critical.
Modelling by a group at the University of Toronto confirmed.
Ashleigh Tuite, an epidemiologist at U of T’s Dalla Lana School of Public Health….said she and her colleagues projected that frontloading vaccine doses would avert between 34 and 42 per cent more symptomatic coronavirus infections, compared with a strategy of keeping half the shipments in reserve.
“It makes much more sense to just get as many people their first doses as soon as possible,” Dr. Tuite said.
…everyone should get the second dose on schedule, but if supply issues delay that injection by a week or two, it shouldn’t hamper how well the vaccines work.
According to Abigail Bimman at Global News, Ontario will now switch to getting as many first doses out as possible:
NEW: Ontario is changing its vaccine policy and no longer reserving second doses, but getting all of the initial 90k out the door- they expect to finish them in the “next several days” – Health Minister’s office tell @globalnew. Change due to confidence in supply chain.
It’s not all the way to first doses first but it’s a minimally risky, smart move. Indeed, Nova Scotia, Saskatchewan and British Columbia already have said that they won’t hold back first doses.
The United States should listen to the wise Canadians.
Latest CDC vaccine distribution and administration numbers are out. Doses Distributed: 11,445,175 Doses Administered: 2,127,143 18.6% of the doses distributed have been administered.
Here is further information. Here is my May Bloomberg column on auctioning off vaccines.