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My Congressional Testimony

I thought the meeting went well. I made four points.

  • It is not too late to do more.
  • We should invest in nasal and oral vaccines.
  • We should vaccinate the world.
  • We should stretch doses through fractional dosing and delaying the second dose, this will be important to vaccinate the world quickly.

One observation. Lots of people are talking about vaccine hesitancy but I am one of the few people who have been talking about nasal and oral vaccines which are the only really solid approach to the issue that I have seen.

My best line:

The unvaccinated are the biggest risk for generating mutations and new variants. You have heard of the South Africa and Brazilian variants, well the best way to protect your constituents from these and other variants is to vaccinate South Africans and Brazilians.

I also got in the last word in Q&A when discussing the pause of J&J:

For the rest of the world it is important to underline that it is most important to get vaccinated now. Use the AstraZeneca vaccine, use the Johnnson & Johnson vaccine…don’t wait for Moderna or Pfizer, it is going to take too long…start your vaccination program early…vaccinate as quickly as possible, that is the route to health and wealth.

See Western Warnings Tarnish Vaccines the World Badly Needs for the beginnings of a disaster. Note that if J&J and AZ are tarnished or knocked out of the vaccine arsenal then dose stretching and investing in more capacity are going to be even more important.

I also submitted five excellent and important pieces to Congress:

Canadian statement on delaying the second dose.

National Advisory Committee on Immunization (NACI) Canada. 2021. “COVID-19 Vaccine Extended Dose Interval for Canadians: NACI Recommendation.” Government of Canada. March 3, 2021. https://www.canada.ca/en/public-health/services/immunization/national-advisory-committee-on-immunization-naci/rapid-response-extended-dose-intervals-covid-19-vaccines-early-rollout-population-protection.html.

Value of vaccine capacity and additional investments.

Castillo, Juan Camilo, Amrita Ahuja, Susan Athey, Arthur Baker, Eric Budish, Tasneem Chipty, Rachel Glennerster, et al. 2021. “Market Design to Accelerate COVID-19 Vaccine Supply.” Science, February. https://doi.org/10.1126/science.abg0889.

Efficacy of the first dose from NEJM.

Skowronski, Danuta, and Gaston Serres De. 2021. “Letter to the Editor on Safety and Efficacy of the BNT162b2 MRNA Covid-19 Vaccine.” New England Journal of Medicine, February 17, 2021. https://doi.org/10.1056/NEJMc2036242.

Overview of dose stretching policies (with links in the online version).

Tabarrok, Alex. 2021. “What Are We Waiting For?” Washington Post, February 12, 2021, sec. Outlook. https://www.washingtonpost.com/outlook/2021/02/12/first-doses-vaccine-rules-fda/

A plan to vaccinate the world.

Agarwal, Ruchir, and Tristan Reed. 2021. “How to End the COVID-19 Pandemic by March 2022” SSRN. 2021. https://documents.worldbank.org/en/publication/documents-reports/documentdetail/181611618494084337/how-to-end-the-covid-19-pandemic-by-march-2022

The whole thing is here. My written testimony is here.

Monday assorted links

1. The FATF crypto recommendations.

2. Markets in everything.

3. “The swan in question has been terrorizing the neighbourhood with its persistent door-knocking over the last five years, residents say.

4. Survey on body-worn police cameras, mostly positive results.

5. Funny (yet sort of true?) that I (along with @pmarca!) am viewed as the big socializer on this list.

6. Vaccinated people should return to greater socializing.  And good news on the South African strain.

Dose Stretching Policies Probably *Reduce* Mutation Risk

One objection to dose-stretching policies, such as delaying the second dose or using half-doses, is that this might increase the risk of mutation. While possible, some immunologists and evolution experts are now arguing that dose-stretching will probably reduce mutation risk which is what Tyler and I concluded. Here’s Tyler:

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.

(See my Washington Post piece for similar arguments and additional references.).

Now here are evolutionary theorists, immunologists and viral experts Sarah Cobey, Daniel B. Larremore, Yonatan H. Grad, and Marc Lipsitch in an excellent paper that first reviews the case for first doses first and then addresses the escape argument. They make several interrelated arguments that a one-dose strategy will reduce transmission, reduce prevalence, and reduce severity and that all of these effects reduce mutation risk.

The arguments above suggest that, thanks to at least some effect on transmission from one dose, widespread use of a single dose of mRNA vaccines will likely reduce infection prevalence…

The reduced transmission and lower prevalence have several effects that individually and together tend to reduce the probability that variants with a fitness advantage such as immune escape will arise and spread (Wen, Malani, and Cobey 2020). The first is that with fewer infected hosts, there are fewer opportunities for new mutations to arise—reducing available genetic variation on which selection can act. Although substitutions that reduce antibody binding were documented before vaccine rollout and are thus relatively common, adaptive evolution is facilitated by the appearance of mutations and other rearrangements that increase the fitness benefit of other mutations (Gong, Suchard, and Bloom 2013; N. C. Wu et al. 2013; Starr and Thornton 2016). The global population size of SARS-CoV-2 is enormous, but the space of possible mutations is larger, and lowering prevalence helps constrain this exploration. Other benefits arise when a small fraction of hosts drives most transmission and the effective reproductive number is low. Selection operates less effectively under these conditions: beneficial mutations will more often be lost by chance, and variants with beneficial mutations are less certain to rise to high frequencies in the population (Desai, Fisher, and Murray 2007; Patwa and Wahl 2008; Otto and Whitlock 1997; Desai and Fisher 2007; Kimura 1957). More research is clearly needed to understand the precise impact of vaccination on SARS-CoV-2 evolution, but multiple lines of evidence suggest that vaccination strategies that reduce prevalence would reduce rather than accelerate the rate of adaptation, including antigenic evolution, and thus incidence over the long term.

In evaluating the potential impact of expanded coverage from dose sparing on the transmission of escape variants, it is necessary to compare the alternative scenario, where fewer individuals are vaccinated (but a larger proportion receive two doses) and more people recover from natural infection. Immunity developing during the course of natural infection, and the immune response that inhibits repeat infection, also impose selection pressure. Although natural infection involves immune responses to a broader set of antibody and T cell targets compared to vaccination, antibodies to the spike protein are likely a major component of protection after either kind of exposure (Addetia et al. 2020; Zost et al. 2020; Steffen et al. 2020), and genetic variants that escape polyclonal sera after natural infection have already been identified (Weisblum et al. 2020; Andreano et al. 2020). Studies comparing the effectiveness of past infection and vaccination on protection and transmission are ongoing. If protective immunity, and specifically protection against transmission, from natural infection is weaker than that from one dose of vaccination, the rate of spread of escape variants in individuals with infection-induced immunity could be higher than in those with vaccine-induced immunity. In this case, an additional advantage of increasing coverage through dose sparing might be a reduction in the selective pressure from infection-induced immunity.

…In the simplest terms, the concern that dose-sparing strategies will enhance the spread of immune escape mutants postulates that individuals with a single dose of vaccine are those with the intermediate, “just right” level of immunity, more likely to evolve escape variants than those with zero or two doses (Bieniasz 2021; Saad-Roy et al. 2021)….There is no particular reason to believe this is the case. Strong immune responses arising from past infection or vaccination will clearly inhibit viral replication, preventing infection and thus within-host adaptation…. Past work on influenza has found no evidence of selection for escape variants during infection in vaccinated hosts (Debbink et al. 2017). Instead, evidence suggests that it is immunocompromised hosts with prolonged influenza infections and high viral loads whose viral populations show high diversity and potentially adaptation (Xue et al. 2017, 2018), a phenomenon also seen with SARS-CoV-2 (Choi et al. 2020; Kemp et al. 2020; Ko et al. 2021). It seems likely, given its impact on disease, that vaccination could shorten such infections, and there is limited evidence already that vaccination reduces the amount of virus present in those who do become infected post-vaccination (Levine-Tiefenbrun et al. 2021).

I also very much agree with these more general points:

The pandemic forces difficult choices under scientific uncertainty. There is a risk that appeals to improve the scientific basis of decision-making will inadvertently equate the absence of precise information about a particular scenario with complete ignorance, and thereby dismiss decades of accumulated and relevant scientific knowledge. Concerns about vaccine-induced evolution are often associated with worry about departing from the precise dosing intervals used in clinical trials. Although other intervals were investigated in earlier immunogenicity studies, for mRNA vaccines, these intervals were partly chosen for speed and have not been completely optimized. They are not the only information on immune responses. Indeed, arguments that vaccine efficacy below 95% would be unacceptable under dose sparing of mRNA vaccines imply that campaigns with the other vaccines estimated to have a lower efficacy pose similar problems. Yet few would advocate these vaccines should be withheld in the thick of a pandemic, or roll outs slowed to increase the number of doses that can be given to a smaller group of people. We urge careful consideration of scientific evidence to minimize lives lost.

Sunday assorted links

1. Rohit Krishnan reviews Stubborn Attachments.

2. “South Korea was the only country in the Organization of Economic Cooperation and Development (OECD) that had total fertility rate below 1 for two consecutive years.

3. Israel-Syria barter markets in everything prisoners for vaccines (NYT).

4. “Mary Beard, a professor of classics at Cambridge University, posited that while Caligula might have been assassinated because he was a monster, it is equally possible that he was made into a monster because he was assassinated.” (NYT)  How much do we really know about the ancient world anyway?

5. Good news on the South African strain.

6. Gelassenheit.

Monday assorted links

1. NYT tech coverage still a train wreck.  And reporters using aliases to stalk non-criminal subjects?  Isn’t that against NYT rules?

2. Scott Sumner on the Romney child plan.

3. Update on South African strain, vaccines, and confidence intervals.

4. Monopsony it ain’t.

5. “The average EV increases overall household load by 2.9 kilowatt-hours per day, less than half the amount assumed by state regulators. Our results imply that EVs travel 5,300 miles per year, under half of the US fleet average. This raises questions about transportation electrification for climate policy.”  Link here.

6. Vaccine efficacy update.

Tuesday assorted links

1. Is the English strain picking up some features of the South African strain? And the new strains do seem somewhat more dangerous.

2. Joe Stiglitz comes perilously close to the Austrian theory of the business cycle.

3. Update on the Russian vaccine (New Yorker).  And this WSJ piece.  It seems to work?  And yet more.

4. ““What we didn’t anticipate was that they would break the law,” Goldenfeld said — that some students, even after testing positive and being told to quarantine, would attend parties anyway.”  A look at some of the models.

5. “Dubai announced Monday the creation of a “space court” to settle commercial disputes, as the UAE — which is sending a probe to Mars — builds its presence in the space sector.”  Link here.

6. My on-line talk to PayPal.  Mostly Q&A, and they did ask me about Nirvana’s “Aneurysm.

7. Incoming vaccine data from Israel.

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.

Sunday assorted links

1. Fauci.  Compare that to revisiting the Balaji thread.

2. Why are grandiose narcissists more effective at organizational politics?

3. Angus and I joke around.

4. What is the quality of CDC software?

5. Migrants to the U.S. are much more productive than migrants to other locales.

6. Atif Mian is still caught up in the Junker Fallacy.

7. Why the South African strain may not become dominant in the U.S.

Friday assorted links

1. The next Michael Lewis book (NYT).

2. Novovax data, including against the South African strain.  And wide confidence intervals.

3. Carolyn Hopkins.

4. Chinese government is collecting Americans’ DNA.

5. John Cochrane on GameStop, etc.

6. And how Robinhood ran out of cash (NYT).  The misinformation in the MR comments section and elsewhere on this is egregious.  Here is yet more common sense, though I don’t quite agree with all the framing.

It is a marathon, not a sprint

For all of its achievements, we still do not know if New Zealand will have ended up doing a good job against Covid-19:

New Zealand’s “go hard, go early” strategy to combat Covid-19 attracted global praise and eliminated local transmission of the virus. But the country’s slow rollout of vaccines is putting people at unnecessary risk and threatens to delay its economic recovery, critics warned.

Wellington plans to start vaccinating frontline workers in April and the general public from July under a cautious strategy that avoids the emergency authorisation of vaccines pursued by crisis-stricken nations such as the US and UK.

And note this:

There are at least 19 cases of the coronavirus variants first identified in the UK or South Africa in managed quarantine facilities in New Zealand for overseas arrivals, according to government data.

And this:

Mr Hipkins said there was “absolutely no complacency” in the government’s response.

Here is the full FT story.

Friday assorted links

1. SinoVac vaccine looking pretty good, and 300 million doses already sold (NYT).  And Pfizer-Biontech seems to work against the South African strain.

2. “Marginal-utility neglect.”

3. Covid in Zambia.

4. Alex redux: why do experiments make people uneasy?

5. Cocanha.

6. Sperm markets in Covid times, and disintermediation (NYT).  Recommended.  But a 1400 chess rating is nothing to boast about!

7. Angry people are more vulnerable to misinformation — Serenity Now!

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.