Category: Medicine

Sudan estimate of the day

…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.

Virginia fact of the day

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).

Hail Britannia!

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.

The *variation* of quality within a given state government

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!

The New Strain and the Need for Speed

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.

Blaming the states yes I do you should too

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.

Jeff Holmes does a CWT with Tyler

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 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!

Those reckless, reckless British, moving to a “first shot” strategy

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.

Wise Canadians

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.

Silvio Gesell’s “stamped vaccine” plan

There are now so many more vaccines distributed than injected into American arms.  How about a simple incentive scheme?  Let’s say you are in group 1A.  You have to come get your vaccine by Jan.3 (??), or otherwise you lose your place in line and are put back into the general pool.  (I’ve heard one report from Israel that non-vaccination leads to cancellation of your health insurance, but this I cannot confirm.)  We can then move onto group 1B more quickly.

And if you are willing to postpone your second shot for three months…

The Omission-Commission Error is Deadly

Britain will start a human challenge trial in January.

The Sun: Imperial College said its joint human challenge study involves volunteers aged 18 to 30, with the project starting in January – and results expected in May.

Initially, 90 volunteers will be given a dose of an experimental nasal vaccine.

They’ll then be deliberately infected with Covid-19.

But this is really just the first part of an excessively cautious study designed to “discover the smallest amount of virus it takes to cause a person to develop Covid-19 infection.” Moreover:

… it’s taken a few months to come to fruition, as before any research could begin the study had to be approved by ethics committees and regulators.

The omission-commission error is deadly. Notice that giving less than one hundred volunteers the virus (commission) is ethically fraught and takes months of debate before one can get approval. But running a large randomized controlled trial in which tens of thousands of people are exposed to the virus is A-ok even though more people may be infected in the latter case than the former and even though faster clinical trials could save many lives. Ethical madness.

How to improve and speed up vaccine allocation, from my email

One issue I haven’t seen discussed is slow throughput of the Vaccine administration, due to a combination of inefficient binning/allocation of distributed vaccines, hesitation to take the vaccine, lack of a central database of available appointments for vaccination, and those time slots potentially going empty if a front line worker misses their appointment, and when there’s no standby/waitlist for people to receive it.

These seems like a use case for a priority queue/heap, which would allow high priority folks to join the queue late but be bumped up to their appropriate priority if they wanted the vaccine, while also allowing those who want the vaccine but are not currently prioritized to get it if there are unallocated supplies.

If prioritization is done (cdc guidelines or not) by restricting who can get it during a particular time period, then it’s guaranteed that throughout won’t be maximized, as all appointment slots won’t be necessarily filled (given the hesitance I’ve heard from people across different levels of education and socioeconomic status) by the allowed demographics at each office where vaccines are available. Meanwhile, there will be those who would gladly take it in an instant who aren’t allowed.

I worry that slow throughput and bad prioritization vaccine administration will keep hospitals indefinitely full, hemorrhaging money, and will thus require a bailout, which I expect will come with medicare4all-style strings attached.

That is from Abhi C., a loyal MR reader.