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Against alcohol, part #6437

Utah’s shift to lower the legal limit for a driver’s blood-alcohol concentration successfully reduced car-crash deaths in its first year of adoption, according to a new report from the National Highway Traffic Safety Administration.

The law, which took effect on Dec. 30, 2018, made Utah the only state in the country in which a driver can be arrested for having a blood-alcohol concentration between .05% and .079%.

NHTSA’s report found that fatal car crashes in Utah were down 5.1% in 2019 from the year before the law went into effect. Nationally, fatal car crashes fell 2% in the same period. Fatal crashes in which alcohol was detected dropped to 38 from 56 in 2019, the first time such crashes declined in three years, Utah Highway Safety Office data shows.

Here is more from the WSJ, via Tim Gillespie.

Writers and status

The problem isn’t that writing generates status, but rather that this status is grossly out of proportion to the wages they are earning in the market. Amongst other problems, this selects for people who value status over wages (often because they are independently financially secure). In this light it’s not surprising the community has become so geographically concentrated – there are enormous rewards to living with the people the most recognize and grant this status. This is not unto itself a problem until that concentration is part of greater demand for what is already some of the most expensive real estate in the world. I’d wager there are more than a few writers with non-trivial followings out there whose Brooklyn lifestyle is a net monetary loss every month. Thats bad, but honestly I think its even worse than it sounds.

And:

Status rewards incentivize geographic concentration, which will in turn intensify herding behavior. If the bulk of your compensation is in-group status, you’re going to want to spend as much time with that group as possible. Your social life will become more important than ever. That also means, however, that anything that might risk disdain or ostracism within the group is to be avoided whenever possible. This means opinions, particularly on subjects that don’t directly impact your life, will tend to become more and more homogeneous over time. It also means hypotheses born of motivated reasoning i.e. the next mayor will be super progressive or want to “defund the police” can acquire a life of their own and quickly evolve from idea spoken aloud in a Brooklyn cocktail bar to universally accepted truth within an insular community. This classic herding phenomenon is relative to the broader world in this case because this particular community spends its working hours delivering the news to us.

Here is more of interest from Michael Makowsky.

Saturday assorted links

1. Engineering milestones for 2022?

2. All of this happened in greater China this week.

3. “…changes in the return to human capital caused by shifts in the supply and demand for educated and skilled labor have played a crucial role in the rise in income inequality since the 1970s – rising corporate concentration and employer market power (monopsony) do not appear to be a key culprit.”  Link here.

4. “Meet the man who runs a moist towelette museum out of a planetarium.

5. Met Opera sings through Omicron (NYT).

6. German trade surplus trending down since 2017.  Are there still people out there who think this is good news?  Remember the bizarre obsession over this issue?  Never reason from a trade surplus!

*The Last King of America*

This biography of King George III is a new and excellent book by Andrew Roberts, who also wrote a great biography of Napoleon. The subtitle of this one is The Misunderstood Reign of George III, and here is one excerpt:

The war was not unwinnable for the British, but they helped to make it so by refusing to change their basic military doctrine and almost anything fundamental at home, in terms of finances, commercial arrangements, conscription and tax levels.  Had Germain possessed the concentration of powers that William Pitt had enjoyed during the Seven Years War, he might have imposed his will on the whole governmental structure, but an overdevolving of competencies between ministries was rife for the first two years of the struggle.  Until 1777, for example, the responsibility for transporting men and their supplies across the Atlantic was divided between the Ordnance Board (responsible for artillery, engineers, guns and gun powder), the Navy Board (men, horses, uniforms, tents, medicine and camp equipment) and the Victualling Board (food), the Treasury being responsible for all other supplies.  This inevitably led to vast amounts of bureaucracy; Germain and Barrington even corresponded over the selection of a single doctor for Howe’s command.  This Whitehall system of waging war had been successful in the Seven Years War at a distance of over 3,000 miles across the ocean, but this was to be much harder without a single leader like Pitt; indeed it has been described as ‘an effort without parallel in the history of the world.’

I found this book especially good for giving the reader a realistic sense of the American Revolution from the British perspective.

Air Pollution Reduces Health and Wealth

Great piece by David Wallace-Wells on air pollution.

Here is just a partial list of the things, short of death rates, we know are affected by air pollution. GDP, with a 10 per cent increase in pollution reducing output by almost a full percentage point, according to an OECD report last year. Cognitive performance, with a study showing that cutting Chinese pollution to the standards required in the US would improve the average student’s ranking in verbal tests by 26 per cent and in maths by 13 per cent. In Los Angeles, after $700 air purifiers were installed in schools, student performance improved almost as much as it would if class sizes were reduced by a third. Heart disease is more common in polluted air, as are many types of cancer, and acute and chronic respiratory diseases like asthma, and strokes. The incidence of Alzheimer’s can triple: in Choked, Beth Gardiner cites a study which found early markers of Alzheimer’s in 40 per cent of autopsies conducted on those in high-pollution areas and in none of those outside them. Rates of other sorts of dementia increase too, as does Parkinson’s. Air pollution has also been linked to mental illness of all kinds – with a recent paper in the British Journal of Psychiatry showing that even small increases in local pollution raise the need for treatment by a third and for hospitalisation by a fifth – and to worse memory, attention and vocabulary, as well as ADHD and autism spectrum disorders. Pollution has been shown to damage the development of neurons in the brain, and proximity to a coal plant can deform a baby’s DNA in the womb. It even accelerates the degeneration of the eyesight.

A high pollution level in the year a baby is born has been shown to result in reduced earnings and labour force participation at the age of thirty. The relationship of pollution to premature births and low birth weight is so strong that the introduction of the automatic toll system E-ZPass in American cities reduced both problems in areas close to toll plazas (by 10.8 per cent and 11.8 per cent respectively), by cutting down on the exhaust expelled when cars have to queue. Extremely premature births, another study found, were 80 per cent more likely when mothers lived in areas of heavy traffic. Women breathing exhaust fumes during pregnancy gave birth to children with higher rates of paediatric leukaemia, kidney cancer, eye tumours and malignancies in the ovaries and testes. Infant death rates increased in line with pollution levels, as did heart malformations. And those breathing dirtier air in childhood exhibited significantly higher rates of self-harm in adulthood, with an increase of just five micrograms of small particulates a day associated, in 1.4 million people in Denmark, with a 42 per cent rise in violence towards oneself. Depression in teenagers quadruples; suicide becomes more common too.

Stock market returns are lower on days with higher air pollution, a study found this year. Surgical outcomes are worse. Crime goes up with increased particulate concentrations, especially violent crime: a 10 per cent reduction in pollution, researchers at Colorado State University found, could reduce the cost of crime in the US by $1.4 billion a year. When there’s more smog in the air, chess players make more mistakes, and bigger ones. Politicians speak more simplistically, and baseball umpires make more bad calls.

As MR readers will know Tyler and I have been saying air pollution is an underrated problem for some time. Here’s my video on the topic:

How do low real interest rates affect optimal tax policy?

Alan Auerbach and William Gale have a new paper on this topic:

Interest rates on government debt have fallen in many countries over the last several decades, with markets indicating that rates may stay low well into the future. It is by now well understood that sustained low interest rates can change the nature of long-run fiscal policy choices. In this paper, we examine a related issue: the implications of sustained low interest rates for the structure of tax policy. We show that low interest rates (a) reduce the differences between consumption and income taxes; (b) make wealth taxes less efficient relative to capital income taxes, at given rates of tax; (c) reduce the value of firm-level investment incentives, and (d) substantially raise the valuation of benefits of carbon abatement policies relative to their costs.

One core intuition here is that as the safe return goes to zero, capital taxes are not especially burdensome compared to consumption taxes.  Of course “the safe return” may not be entirely well-defined within a corporate context, and capital taxes often hit returns to risk as well, so this is a bit more complicated than the abstract alone would indicate.

The authors also offer this intuition, which I do not quite follow:

In simplified environments, a wealth tax can be written as an equivalent tax on capital income. As the rate of return falls, the equivalent income tax rate of any given wealth tax rises. That is, a given wealth tax rate becomes more distortionary relative to a given capital income tax as the rate of return falls.

One of my biggest worries about a wealth tax is that it takes resources away from people who at the margin seem to be good at generating extra-normal returns.  That comparative advantage might be more important as the safe rate goes to zero.  So I am fine with the conclusion of the authors, but not sure if their intuition is equivalent to mine (I suspect it is not).

This one is clearer to me:

A major focus of potential tax reform has been the treatment of capital gains, given their tax-favored status, their high concentration among the very wealthy, and the distortions that the current method of taxation causes. A key element of the current system of capital gains taxation
is the lock-in effect, which discourages the realization of gains to take advantage of deferral of taxation. With very low interest rates, the deferral advantage loses much of its relevance, and this can make relatively simple reforms (such as taxing capital gains at death) achieve results very similar to more complicated schemes (such as taxing capital gains on accrual, even when not realized).

Overall this paper is very interesting and thought-provoking.  Nonetheless, until we understand better why the safe rate of return has diverged so radically from “typical” (but still risky) corporate rates of return, I am not sure what implications we can draw from the model.

The NYTimes on the FDA and Rapid Tests

In July of 2020 I wrote in Frequent, Fast, and Cheap is Better than Sensitive:

A number of firms have developed cheap, paper-strip tests for coronavirus that report results at-home in about 15 minutes but they have yet to be approved for use by the FDA because the FDA appears to be demanding that all tests reach accuracy levels similar to the PCR test. This is another deadly FDA mistake.

…The PCR tests can discover virus at significantly lower concentration levels than the cheap tests but that extra sensitivity doesn’t matter much in practice. Why not? First, at the lowest levels that the PCR test can detect, the person tested probably isn’t infectious. The cheap test is better at telling whether you are infectious than whether you are infected but the former is what we need to know to open schools and workplaces.

It’s great that other people including the NYTimes are now understanding the problem. Here is the excellent David Leonhardt in Where are the Tests?

Other experts are also criticizing the Biden administration for its failure to expand rapid testing. Even as President Biden has followed a Covid policy much better aligned with scientific evidence than Donald Trump’s, Biden has not broken through some of the bureaucratic rigidity that has hampered the U.S. virus response.

In the case of rapid tests, the F.D.A. has loosened its rules somewhat over the past year, allowing the sale of some antigen tests (which often cost about $12 each). But drugstores, Amazon and other sellers have now largely run out of them. I tried to buy rapid tests this weekend and couldn’t find any.

The F.D.A.’s process for approving rapid tests is “onerous” and “inappropriate,” Daniel Oran and Dr. Eric Topol of Scripps Research wrote in Stat News.

For the most part, the F.D.A. still uses the same cumbersome process for approving Covid tests that it uses for high-tech medical devices. To survive that process, the rapid tests must demonstrate that they are nearly as sensitive as P.C.R. tests, which they are not.

But rapid tests do not need to be so sensitive to be effective, experts point out. P.C.R. tests often identify small amounts of the Covid virus in people who had been infected weeks earlier and are no longer contagious. Rapid tests can miss these cases while still identifying about 98 percent of cases in which a person is infectious, according to Dr. Michael Mina, a Harvard epidemiologist who has been advocating for more testing

Identifying anywhere close to 98 percent of infectious cases would sharply curb Covid’s spread. An analysis in the journal Science Advances found that test frequency matters more for reducing Covid cases than test sensitivity.

As I said on twitter what makes the FDA’s failure to approve more rapid antigen tests especially galling is that some of the tests being sold cheaply in Europe are American tests just ones not approved in the United States. If it’s good enough for the Germans it’s good enough for me!

Growing Oligopolies, Prices, Output, and Productivity

The real monopoly problems in our economy are not the firms that push up some very particular concentration indices, rather they are the small, local monopolies, hospitals, and the public education system.  Here is a new investigation (AEA gate) from Sharat Ganapati, you will note that the bold emphasis has been added by yours truly:

American industries have grown more concentrated over the last 40 years. In the absence of productivity innovation, this should lead to price hikes and output reductions, decreasing consumer welfare. With US census data from 1972 to 2012, I use price data to disentangle revenue from output. Industry-level estimates show that concentration increases are positively correlated to productivity and real output growth, uncorrelated with price changes and overall payroll, and negatively correlated with labor’s revenue share. I rationalize these results in a simple model of competition. Productive industries (with growing oligopolists) expand real output and hold down prices, raising consumer welfare, while maintaining or reducing their workforces, lowering labor’s share of output.

That is from the new issue of American Economic Journal: Microeconomics.  Rooftops!  Other research has pointed in the same direction.  Pennsylvania, Ave.: please do not split up America’s best and most productive firms.

The Biden Executive Order on promoting competition

Here is the text, I won’t attempt a summary but here are some running comments:

1. The beginning of the piece suggests that concentration is rising in the American economy.  But this probably isn’t true.  See also these comments by me.

2. Industry concentration has not driven wages down by “as much as 17%” — that’s a porky!  OK, they say “advertised wages,” but come on…

3. I am happy to see the document take on occupational licensing.

4. Contra to the recommendation, we should not ban non-compete agreements outright.  Many non-compete agreements are perfectly normal institutions designed to protect corporate assets against IP theft, client lists for instance.  We should restrict non-compete agreements in some more sophisticated manner, still to be determined.

5. Lower prescription drug prices?  Maybe.  Do they estimate the elasticity of supply?  No.  Thus this discussion would fail my Econ 101 class.  We do know, however, that prescription drugs are one of the very cheapest ways our health care system saves lives, so this is not obviously a good idea.

6. Right to repair laws?  Again, maybe.  But show me the trade-off and cite a cost-benefit analysis.  If software gives more consumer surplus to consumers (again, a maybe), should we be wanting to tax it with contractual restrictions?  Should we be wanting to tax Tesla right now?

7. Portability of bank account information is a good idea.

8. “Empower family farmers…” — do you even need to know what comes next?  Aarghh!!!

9. The order “encourages” the DOJ and FTC to take various actions.  I won’t blame Biden for this, but we’ve way overstepped what executive orders should be doing, some time ago.  The net feeling the honest reader of this section receives is that our antitrust policies toward the large tech companies are not based in much of a notion of rule of law.

10. Should HHS “standardize plan options” in the NHIM to make price shopping easier?  Makes me nervous — diverse market offerings can be good.

11. Lots of tired and not typically true claims and insinuations about concentration in airline markets; see my book Big Business or read Gary Leff.  And shouldn’t airlines charge for bags?  Maybe yes, maybe no, but prices per item are not in general a bad thing.

12. We are warned that farmers and ranchers take in an ever-smaller share of the food dollar spent — thank goodness!  And there are a bunch of other selective, scattered observations about food prices (“corn seed prices have gone up as much as 30% annually…”), but nothing close to systematic or showing an actual market failure (corn prices by the way have been plummeting since 2012).

13. Broadband policy should indeed be improved, but this section reads as messy, should do more to emphasize the notion of competition and common carrier platforms, and how about a mention of StarLink?

14. There’s not really any point in marching through a discussion of the “Big Tech” section.

15. Is there a problem with bank concentration in this country?  Not where I live.  Maybe in some rural areas?

16. YIMBY > NIMBY would do more to limit market power than just about anything else, by the way.

17. Is there even a peep about this country’s biggest and worst-performing monopoly in K-12?  Of course not.  It is Amazon you have to worry about!

So overall this is not great economics.  It is good to see the Biden administration pick up on a few pro-competition issues, but much of the document is not clearly pro-competition either.  The reasoning and evidence are pretty much politicized from start to finish.

Use Fractional Dosing to Speed Vaccination and Save Lives

I’ve been shouting about fractional dosing since January, most recently with my post A Half Dose of Moderna is More Effective Than a Full Dose of AstraZeneca and the associated paper with Michael Kremer and co-authors. Yesterday we saw some big movement. Writing in Nature Medicine, WHO epidemiologists Benjamin Cowling and Wey Wen Lim and evolutionary biologist Sarah Cobey title a correspondence:

Fractionation of COVID-19 vaccine doses could extend limited supplies and reduce mortality.

Exactly so. They write:

Dose-finding studies indicate that fractional doses of mRNA vaccines could still elicit a robust immune response to COVID-192,3. In a non-randomized open-label phase 1/2 trial of the BNT162b2 vaccine, doses as low as one third (10 μg) of the full dose produced antibody and cellular immune responses comparable to those achieved with the full dose of 30 μg (ref. 4). Specifically, the geometric mean titer of neutralizing antibodies 21 days after the second vaccine dose was 166 for the group that received 10 μg, almost the same as the geometric mean titer of 161 for the group that received 30 μg, and 63 days after the second dose, these titers were 181 and 133, respectively4. For the mRNA-1273 vaccine, a dose of 25 μg conferred geometric mean PRNT80 titers (the inverse of the concentration of serum needed to reduce the number of plaques by 80% in a plaque reduction neutralization test) of 340 at 14 days after the second dose, compared with a value of 654 for the group that received the standard dose of 100 μg (ref. 5). According to the model proposed by Khoury et al.6, if vaccine efficacy at the full dose is 95%, a reduction in dose that led to as much as a halving in the post-vaccination geometric mean titer could still be in the range of 85–90%. Although other components of the immune response may also contribute to efficacy, these dose-finding data are at least indicative of the potential for further exploration of fractionation as a dose-sparing strategy. Durability of responses after fractional doses should also be explored.

…Concerns about the evolution of vaccine resistance have been posited as a potential drawback of dose-sparing strategies. However, vaccines that provide protection against clinical disease seem to also reduce transmission, which indicates that expanding partial vaccination coverage could reduce the incidence of infection. As described in a recent paper, lower prevalence should slow, not accelerate, the emergence and spread of new SARS-CoV-2 variants8.

…In conclusion, fractionated doses could provide a feasible solution that extends limited supplies of vaccines against COVID-19, which is a major challenge for low- and middle-income countries.

Also a new paper in preprint just showed that 1/4 doses of Moderna create a substantial and lasting immune response on par with that from natural infection.

Here we examined vaccine-specific CD4+ T cell, CD8+ T cell, binding antibody, and neutralizing antibody responses to the 25 ug Moderna mRNA-1273 vaccine over 7 months post-immunization, including multiple age groups, with a particular interest in assessing whether pre-existing crossreactive T cell memory impacts vaccine-generated immunity. Low dose (25 ug) mRNA-1273 elicited durable Spike binding antibodies comparable to that of convalescent COVID-19 cases. Vaccine-generated Spike memory CD4+ T cells 6 months post-boost were comparable in quantity and quality to COVID-19 cases, including the presence of TFH cells and IFNg-expressing cells.

Finally, an article in Reuters notes that Moderna are preparing to launch a 50 ug dose regimen as a booster and for children. Thus, contrary to some critics of our paper, the technology is ready.

Frankly, governments are way behind on this–they should have been pushing the vaccine manufacturers and funding trials on alternative dosing since at least January. Indeed, imagine how many lives we might have saved had we listened to Operation Warp Speed advisor Moncef Slaoui who advocated for half doses in January. On a world scale, we could have vaccinated tens even hundreds of millions more people by now had we ramped up fractional dosing.

At this point, it’s my view that there is enough knowledge to justify rolling out alternative dosing in any hot spot or in any country worried about outbreaks. Roll it out in a randomized fashion (as Kominers and I discussed in the context of the US vaccination rollout) to study it in real time but start the roll out now. Lives can be saved if we speed up vaccination, especially of the best vaccines we have, the mRNAs. Moderna and Pfizer have together pledged to deliver (mostly Pfizer and mostly through the US) some 250m vaccine doses to COVAX in 2021 for delivery to less developed countries. If we go to half-doses that becomes 500m doses–a life saver. And recall these points made earlier:

Judging by neutralizing antibodies, a 50 ug dose of, for example, Moderna looks to be more effective than standard dosing of many other vaccines including AZ and J&J and much better than others such as Sinovac. Thus alternative dosing is a way to *increase* the quality of vaccine for many people.

A 50 ug dose vaccine available today is much higher quality than a 100 ug dose vaccine available one year from now.

If we have the will, we can increase vaccine supply very rapidly.

Long COVID in a prospective cohort of home-isolated patients

Long-term complications after coronavirus disease 2019 (COVID-19) are common in hospitalized patients, but the spectrum of symptoms in milder cases needs further investigation. We conducted a long-term follow-up in a prospective cohort study of 312 patients—247 home-isolated and 65 hospitalized—comprising 82% of total cases in Bergen during the first pandemic wave in Norway. At 6 months, 61% (189/312) of all patients had persistent symptoms, which were independently associated with severity of initial illness, increased convalescent antibody titers and pre-existing chronic lung disease. We found that 52% (32/61) of home-isolated young adults, aged 16–30 years, had symptoms at 6 months, including loss of taste and/or smell (28%, 17/61), fatigue (21%, 13/61), dyspnea (13%, 8/61), impaired concentration (13%, 8/61) and memory problems (11%, 7/61). Our findings that young, home-isolated adults with mild COVID-19 are at risk of long-lasting dyspnea and cognitive symptoms highlight the importance of infection control measures, such as vaccination.

That is from a new Nature paper by Bjørn Blomberg, et.al. Via SK.  On vaccinating the young, here are further relevant observations from Francois Balloux.

Which are the most striking elements of Monkey Pong?

Watch this if you haven’t already:

What comes to your mind is an interesting kind of Rorschach test.  A few options (not necessarily endorsed by me) are:

1. Where did they get that background from?

2. Can I have some of what that monkey is drinking?

3. Wealth concentrations are going to make IRB regulations less relevant over time.

4. How many people want to play Pong against a wired monkey?  Will we employ or enslave monkeys to enable this?  What is in fact the relevant difference?

5. What else can that monkey (cognitively) do better than I can?

6. Which regulatory agency will have jurisdiction over the (presumably disabled) humans who want this as a medical treatment?  What about the non-disabled humans?  The Navy pilots?

7. Where does this all end?

8. Will this raise or lower the price of monkeys?

What else?

A Miniature Masterpiece

Superb NYTimes disquisition on a masterpiece of Indian miniature painting. The text, formatting, visuals, all beautifully done–better than any museum exhibit I can recall.

In addition to the subject matter this piece has a lot to say about online education and how news is becoming a winner take-most market. Note what Tyler and I said on endogenous fixed costs in our piece on online education in the AER and consider how many newspapers could put together a display of this quality.

Shaked and Sutton (1987) and Sutton (1998) show that when quality is primarily vertical, meaning that there is a measure of quality such that all consumers agree that higher quality is more preferred, then increased market size does not result in reduced concentration. Instead, as market size increases, firms invest more in quality, which endogenously increases economies of scale and maintains market concentration.

Along related lines, Berry and Waldfogel (2010) show that there are many more restaurants in larger than smaller cities, but even as city size increases by a factor of 10 there is no tendency for the number of newspapers to increase. Larger cities have more restaurants than smaller cities because economies of scale are limited and quality differs “horizontally,” according to taste (thus, larger cities have more diverse restaurants). Yet larger cities are served by roughly the same number of newspapers as smaller cities because quality is more vertical, most newspaper consumers want more coverage, better writers and more features.

Addendum: Tim and Marcos remind of previous items in this series which I also loved, The Birth of the Self Portrait and A Picture of Change.

Canada: An Official Strong Recommendation for First Doses First

Canada’s National Advisory Committee on Immunization (NACI), a scientific advisory group to the government, has made a forceful and dramatic statement strongly favoring First Doses First (delay the second dose.) This is a very big deal for the entire world. Basically NACI have endorsed everything that Tyler and I have said on First Doses First since my first post tentatively raised the issue on December 8. I am going to quote this statement extensively since it’s an excellent summary. No indentation.

—-NACI Statement—-

Based on emerging evidence of the protection provided by the first dose of a two dose series for COVID-19 vaccines currently authorized in Canada, NACI recommends that in the context of limited COVID-19 vaccine supply jurisdictions should maximize the number of individuals benefiting from the first dose of vaccine by extending the second dose of COVID-19 vaccine up to four months after the first. NACI will continue to monitor the evidence on effectiveness of an extended dose interval and will adjust recommendations as needed. (Strong NACI Recommendation)

    • In addition to emerging population-based data, this recommendation is based on expert opinion and the public health principles of equity, ethics, accessibility, feasibility, immunological vaccine principles, and the perspective that, within a global pandemic setting, reducing the risk of severe disease outcomes at the population-level will have the greatest impact. Current evidence suggests high vaccine effectiveness against symptomatic disease and hospitalization for several weeks after the first dose, including among older populations.

Protecting individuals

  • By implementing an extended four month interval strategy, Canada will be able to provide access to first doses of highly efficacious vaccines to more individuals earlier which is expected to increase health equity faster. Canada has secured enough vaccines to ensure that a second dose will be available to every adult.
  • As a general vaccination principle, interruption of a vaccine series resulting in an extended interval between doses does not require restarting the vaccine series. Principles of immunology, vaccine science, and historical examples demonstrate that delays between doses do not result in a reduction in final antibody concentrations nor a reduction in durability of memory response for most multi-dose products.
  • Assessment of available data on efficacy and effectiveness of a single dose of mRNA vaccine was a critical factor in assessing the impact of a delayed second dose at this time. The two available clinical trials for mRNA vaccines (Pfizer-BioNTech and Moderna) provide evidence that indicates that efficacy against symptomatic disease begins as early as 12 to 14 days after the first dose of the mRNA vaccine. Excluding the first 14 days before vaccines are expected to offer protection, both vaccines showed an efficacy of 92% up until the second dose (most second doses were administered at 19-42 days in the trials). Recently, real world vaccine effectiveness data presented to or reviewed by NACI assessing PCR-positive COVID-19 disease and/or infection from Quebec, British Columbia, Israel, the United Kingdom and the United States support good effectiveness (generally 70-80%, depending on the methodology used and outcomes assessed) from a single dose of mRNA vaccines (for up to two months in some studies). While studies have not yet collected four months of data on effectiveness of the first dose, the first two months of population-based effectiveness data are showing sustained and high levels of protection. These data include studies in health care workers, long term care residents, elderly populations and the general public. While this is somewhat lower than the efficacy demonstrated after one dose in clinical trials, it is important to note that vaccine effectiveness in a general population setting is typically lower than efficacy from the controlled setting of a clinical trial, and this is expected to be the case after series completion as well.
  • Published data from the AstraZeneca clinical trial indicated that delaying the second dose to ≥ 12 weeks resulted in a better efficacy against symptomatic disease compared to shorter intervals between doses.
  • The duration of protection from one or two doses of COVID-19 vaccines is currently unknown. Experience with other multi-dose vaccines after a single dose suggests persistent protection could last for six months or longer in adolescents and adults. Longer-term follow-up of clinical trial participants and those receiving vaccination in public programs will assist in determining the duration of protection following both one and two doses of vaccination. NACI will continue to monitor the evidence on effectiveness of an extended interval, which is currently being collected weekly in some Canadian jurisdictions, and will adjust recommendations as needed if concerns emerge about waning protection.

Protecting populations

  • Although effectiveness after two-doses will be somewhat higher than with one dose, many more people will benefit from immunization when extending the interval between doses in times of vaccine shortage; offering more individuals direct benefit and also the possibility of indirect benefit from increasing population immunity to COVID-19 disease. Everyone is expected to obtain the full benefit of two doses when the second dose is offered after 4 months.
  • Internal PHAC modelling reviewed by NACI based on Canadian supply projections suggested that accelerating vaccine coverage by extending dose intervals of mRNA vaccines could have short-term public health benefits in preventing symptomatic disease, hospitalizations, and deaths while vaccine supply is constrained. Even a theoretical scenario analysis in which intervals were extended up to six months and protection was lost at a rate of 4% per week after the first dose also showed that extending the mRNA vaccine dose intervals would still have public health benefits. External modelling results have also suggested that extending dose intervals can avert infections, hospitalizations and deaths.
  • The impact on variants of concern by extending the interval between doses is unknown, but there is currently no evidence that an extended interval between doses will either increase or decrease the emergence of variants of concern. COVID-19 mRNA vaccines and AstraZeneca vaccine have shown promising early results against variant B.1.1.7. As effectiveness of the first dose against other variants of concern is emerging, ongoing monitoring will be required.
  • Vaccine distribution will be optimized through this strategy, and current vaccine supply projections will work well with an extended dose strategy that aims to immunize as many Canadians as efficiently as possible. Extending the dose intervals for mRNA vaccines up to four months has the potential to result in rapid immunization and protection of a large proportion of the Canadian population….