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Why is inflation so bad?

That is the theme of my latest Bloomberg column, here is part of the final bit:

I am left with two major worries. First, higher rates of inflation redistribute wealth in a disruptive manner. For better or worse, more and more Americans are employed in the relatively bureaucratic service sector, which includes education, health care and government. If price inflation spikes as high as 6%, most of those workers do not rapidly receive an offsetting wage hike to restore their previous standards of living.

They might get higher pay by getting a new job, or by credibly threatening to leave. But that’s often a tense and unsettling position, from both a personal and professional standpoint. People might even have received stimulus dollars earlier in the pandemic, either directly or indirectly, and thus broken even or come out ahead. Still, with inflation, they will experience a loss of purchasing power, and they will hate it.

The second major worry is that inflation tends to require a subsequent disinflation, if only because people hate inflation so much. And we macroeconomists know that disinflations (or outright deflations) tend to bring recessions. When the U.S. Federal Reserve tightens monetary policy by a significant amount, aggregate demand in the economy falls, leading to losses in output and employment.

Of course, that’s a funny way of explaining why higher rates of price inflation are bad: Essentially, inflation is bad because it has to end. A subtler version of this theory is that workers and voters have only a limited tolerance for disruptions — and when they occur, we end up making blunders in our efforts to get out of them.

The proper critique of inflation is thus quite general. A pandemic is also a disruption, and we’ve made many mistakes in our efforts to end that as well. One of those mistakes, in fact, has been excess inflation. It will not be our last mistake, as we are still building our ever-widening circle of errors.

Recommended.

Tuesday assorted links

1. Creeque Alley (that was then, this is now).

2. “We further document that the labor-market premium to action-oriented personality traits has rapidly increased over the past two decades.”  And here is a new paper on Finnish extraversion (not joking).

3. Banning non-compete agreements in Austria didn’t really help worker earnings.

4. On the benefit of early promotion.  Suandi is on the job market from Berkeley.

5. “We find that the introduction of potatoes led to a sizeable and permanent reduction in conflict.”  Joris Mueller on the market from Northwestern.

6. Lots of interesting job market candidates from Northwestern this year in economic history, political economy.

Clement and Tribe Predicted the FDA Catastrophe

Paul Clement and Laurence Tribe

Laboratory developed tests are not FDA regulated–never have been–instead the labs are regulated under the Clinical Laboratory Improvement Amendments (CLIA) as overseen by the CMS. Laboratory developed tests are the kind your doctor orders, they are a service not a product and are not sold directly to patients. Labs develop new tests routinely and they do not apply to the FDA for approval. Despite this long history, the FDA has claimed that it has the right to regulate lab tests and they have merely chosen not to exercise this right for forty years. In 2015, Paul Clement the former US Solicitor General under George W. Bush and Laurence Tribe, considered by many to be the leading constitutional lawyer in the United States, wrote an article that rejected the FDA’s claims writing that the “FDA’s assertion of authority over laboratory-developed testing services is clearly foreclosed by the FDA’s own authorizing statute” and “by the broader statutory context.”

Despite lacking statutory authority, the FDA has continued to claim it is authorized to regulate laboratory tests. Indeed, a key failure in the pandemic happened when the FDA issued so-called “guidance documents” saying that any SARS-CoV-II test had to be pre-approved by the FDA. Thus, the FDA reversed the logic of emergency. In ordinary times, pre-approval was not necessary but when speed was of the essence it became necessary to get FDA pre-approval. The FDA’s pre-approval process slowed down testing in the United States and it wasn’t until after the FDA lifted its restrictions in March that tests from the big labs became available.

Clement and Tribe rejected the FDA claims of regulatory authority over laboratory developed tests on historical, statutory, and legal grounds but they also argued that letting the FDA regulate laboratory tests was a dangerous idea. In a remarkably prescient passage, Clement and Tribe (2015, p. 18) warned:

The FDA approval process is protracted and not designed for the rapid clearance of tests. Many clinical laboratories track world trends regarding infectious diseases ranging from SARS to H1N1 and Avian Influenza. In these fast-moving, life-or-death situations, awaiting the development of manufactured test kits and the completion of FDA’s clearance procedures could entail potentially catastrophic delays, with disastrous consequences for patient care.

Clement and Tribe nailed it. Catastrophic delays, with disastrous consequences for patient care is exactly what happened.

Addendum: See also my pre-pandemic piece on this issue, Our DNA, Our Selves.

Monday assorted links

1. Jodi Ettenberg interview.  Recommended.

2. “No evidence for cumulating socioeconomic advantage. Ability explains increasing SES effects with age on children’s domain test scores.

3. Unite America, for ranked choice voting.  And the sugar lobby is alive and well.

4. “We find that access to a plasma donation center reduces demand (inquiries) for payday and installment loans by 6.5% and 8.1%, respectively, with larger effects (13.1% and 15.7%, respectively) on younger borrowers. Moreover, foot traffic increases by 7-10% at essential and non-essential goods establishments when a new plasma center opens nearby. Our findings suggest that plasma donation helps households smooth consumption without appealing to high-cost debt.”  Link here.

5. “Thus, six-year-olds appear to more flexibly use multiple sources of information than both younger children and adults…

6. “An additional study (N = 2,172) shows that both Democrats and Republicans perceived the social network Facebook to be biased against their side.

7. “License plate readers are rapidly reshaping private security in American neighborhoods, bringing police surveillance tools to the masses with an automated watchdog that records 24 hours a day.

Who are the best Irish artists?, part III, Mainie Jellett

Mainie Jellett, 1897-1944, born in Dublin to a well-to-do Protestant family of Huguenot origin.  She studied with William Orpen in Dublin and then moved to England, where she developed an attractive figurative style.  But soon thereafter her work turned abstract  when she studied Cubism in Paris in the early 1920s.  She was part of what might be the most significant (and rapid) revolution in the history of art, although the Irish branch of that revolution usually receives little attention.  She and Evie Hone led the introduction of modern art to Ireland, and arguably still represent the peak of that tradition.  “Like James Joyce, who had ‘not become modern to the extent that he ceased to be Irish’, Jellett made modernism Irish.” (source)

She blended cubism on top of Christian devotional ideas and also structures and images from the Book of Kells and other medieval Celtic sources.  At its best, her work is just perfect — you would not wish for the curves or angles or colors to go any other way.  Here is a classic Jellett image, also drawing on some Chinese influences:

Here is her painting “Abstract Crucifixion”:

For a point of contrast, see her homage to Fra Angelico.  Her Anglo-Irish background led to some hostility, and her deliberate invocation of specifically Catholic images is sometimes interpreted as a project for Irish cultural reconciliation.

Here is a less typical but still fine representational work:

I can’t bring myself to call her the greatest Irish artist ever, as perhaps she is not tops in breadth or multiplicity of perspectives, but she was one of the very best and I do not tire of viewing her work.  She is the equal of many of the better-known modernist artists from other countries and she excelled also in watercolors and sketches.  Her life was cut tragically short by pancreatic cancer.

Why isn’t there more debate over the Biden economic plan?

That is the topic of my latest Bloomberg column, here is one bit:

My colleague Arnold Kling put it well: “With the reconciliation bill, there is no attempt to convince the public that it is desirable to enact an enormous child tax credit or to mandate ending use of fossil fuels in a decade. Instead, what we read is that if you’re on the blue team you want the number to be 3.5, but a few Democrats are holding out for something lower.”

The Democrats say they might be considering a carbon tax to fund their spending plans, and also to address climate change. You might have expected this news to be on the front page every day, and a dominant topic on Twitter and Substack. Isn’t the fate of the planet at stake, or perhaps an economic depression, depending on your point of view?

There was a lengthy and well-done article in the Washington Post on the political risks associated with this plan. It appeared on Page A21 of the paper edition.

And:

The contrast with earlier but still recent times is obvious. As recently as Barack Obama’s presidency, there was a vigorous policy debate on just about every proposal. A fiscal stimulus of $800 billion? That one was hashed out for months, with detailed takes on the multiplier, the liquidity trap and the marginal propensity to consume, coming from all points of view. Then there was Obamacare, which led to even more passionate and detailed debate over the course of years. Who didn’t have an opinion about the “Cadillac tax” or the proper size of the mandate penalty?

And why has this shift occurred?:

One possibility is that the substantive conversations are occurring on private channels, such as WhatsApp, or in person. This leaves the public sphere a relatively empty shell. Another possibility, more depressing yet, is that the main debate is now about political power and tactics, rather than policy per se. Squabbles over symbols are more common than disagreements over substance, and the influence of various interest groups matters more than the strength of any argument.

Another possibility I did not mention is that perhaps (since DT?) the news cycle has been shifting so rapidly that it no longer very easily sustains this older-fashioned style of ongoing debate?  What might some other reasons be?

Why the defenses of Australia do not persuade me

Alex laid out some complaints about Covid policy down under, I have been receiving emails and tweets arguing the following:

1. Australia is choosing a perfectly acceptable point on the liberty vs. safety frontier.

2. The Australian decision to do extreme lockdowns is democratic, and most Australians support it.

And sometimes I see a third point, which as far as I can tell is true:

3. Australia doesn’t have much in the way of ICU excess capacity, so a Covid surge would hit the country especially hard.

I think those responses, however, are missing the point of the critique.  I would stress that if Covid risk has you with your back against the wall and the government is forcing extremely restrictive measures on your citizenry, you should be implementing the following in an urgent manner:

a. Twice a week rapid antigen tests for everyone.  (Plenty of time to prep for this one.)

b. Much stronger incentives to vaccinate people more rapidly, including with the large stock (six million or so?) of AstraZeneca vaccines.  Demand side incentives, supply side incentives, whatever can be done.  Let’s throw the kitchen sink at this one.  But as it stands, I just don’t see the urgency.

c. Mobile monoclonal antibody units, as they are used in Florida (modest progress here).

d. Maybe other emergency measures too?  I’ve been hearing for decades that Australia has such a great health care system so surely they can make lots of progress on these and other fronts?

As far as I can tell from this great distance, Australia is doing none of these.  And, while there is some disquiet about lockdowns, few of its citizens are demanding that they do any of those positive measures.  Not many of its well-known politicians are proposing those ideas either.  (Please feel free to correct me if that is wrong!…but I just don’t see word of it on-line.)

If Australia implemented all of those policies, or even just one of them, they could attain a much better “liberty vs. lives” frontier, no matter where you think the government should end up on that frontier.  They could save lives, and enjoy more liberty.

And that is the great shame and indeed I would say crime.  There seems to be an incredible complacency that people in some parts of the country will put up with the current measures and not demand the government look for more practical measures to boost both liberty and security.

So when you write me and suggest “this is democratic and the people approve,” yes that is exactly the problem.

Gaming is coming to get us

That is the theme of my latest Bloomberg column, the first part concerns culture, but here is the section on government regulation:

The self-contained nature of games also means they will be breaking down government regulation. Plenty of trading already takes place in games — involving currencies, markets, prices and contracts. Game creators and players set and enforce the rules, and it is harder for government regulators to play a central role.

The lesson is clear: If you wish to create a new economic institution, put it inside a game. Or how about an app that gamifies share trading? Do you wish to experiment with a new kind of stock exchange or security outside the purview of traditional government regulation? Try the world of gaming, perhaps combined with crypto, and eventually your “game” just might influence events in the real world.

To date the regulators have tried to be strict. It is currently difficult to build fully realized new worlds without creating something that is legally defined as an unregistered security. Those regulations don’t receive a lot of attention from the mainstream media, but they are rapidly becoming some of the most significant and restrictive rules on the books.

At the same time, regulators are already falling behind. Just as gaming has outraced the world of culture, so will gaming outrace U.S. regulatory capabilities, for a variety of reasons: encryption, the use of cryptocurrency, the difficulties of policing virtual realities, varying rules in foreign jurisdictions and, not incidentally, a lack of expertise among U.S. regulators. (At least the Chinese government’s attempt to restrict youth gaming to three hours a week, while foolhardy, reflects a perceptive cultural conservatism.)

Both the culture-weakening and the regulation-weakening features of games follow from their one basic characteristic: They are self-contained worlds. Until now, human institutions and structures have depended on relatively open and overlapping networks of ideas. Gaming is carving up and privatizing those spaces. This shift is the big trend that hardly anyone — outside of gaming and crypto — is noticing.

If the much-heralded “metaverse” ever arrives, gaming will swallow many more institutions, or create countervailing versions of them. Whether or not you belong to the world of gaming, it is coming for your worlds. I hope you are ready.

And the piece has a good footnote on how gaming relates to postmodernism.

Authoritarian Australia

Australia is now one of the most authoritarian states in the world. Conor Friedersdorf writes:

Australia is undoubtedly a democracy, with multiple political parties, regular elections, and the peaceful transfer of power. But if a country indefinitely forbids its own citizens from leaving its borders, strands tens of thousands of its citizens abroad, puts strict rules on intrastate travel, prohibits citizens from leaving home without an excuse from an official government list, mandates masks even when people are outdoors and socially distanced, deploys the military to enforce those rules, bans protest, and arrests and fines dissenters, is that country still a liberal democracy?

As I noted earlier, Australia is in clear contravention of the UN Declaration of Human Rights, Article 13 of which states:

  1. Everyone has the right to freedom of movement and residence within the borders of each state.
  2. Everyone has the right to leave any country, including his own, and to return to his country.

Friedersdorf continues:

To give Australia’s approach its due, temporary restrictions on liberty were far more defensible early in the pandemic…Had it behaved rationally and adequately valued liberty, a rich nation like Australia would have spent lavishly—before knowing which vaccines would turn out to be most effective—to secure an adequate supply of many options for its people. It could afford to eat the cost of any extra doses and donate them to poorer countries. Australia then could have marshaled its military and civil society to vaccinate the nation as quickly as possible, lifted restrictions more fully than Europe and the United States did, and argued that the combination of fewer deaths and the more rapid return to normalcy made their approach a net win.

Instead, Australia invested inadequately in vaccines and, once it acquired doses, was too slow to get them into arms. “Of the 16 million doses of the AstraZeneca vaccine that have been released to the government by manufacturer CSL, only about 8 million have gone into the arms of Australians,” The Age reported on August 21, citing concern about blood clots and a widespread preference for the Pfizer vaccine.

…Because of its geography, Australia is a neighbor and an observer of authoritarian countries as varied as China and Singapore. But its own fate, too, may turn on whether its people crave the feeling of safety and security that orders from the top confer, or whether they want to be free.

Australians largely support the restrictions but to me that makes them all the more disturbing.

Temporary restrictions on liberty can be justified in an emergency if the restrictions produce something else of great value but respecting the great value of liberty and individual rights means doing everything in one’s power to limit the scope of and lift such restrictions as quickly and completely as possible.

Saturday assorted links

1. Private insurers are now picking up less of the tab for Covid-related hospital stays.

2. Claims about vaccine efficacy, useful.  And further claims about boosters.  The correct final picture here still is not clear to me.

3. Dishonesty update.

4. Progress in the use of monoclonal antibodies.  Sadly: “For the administration, mum’s the word on monoclonal antibodies, rapid home tests, high quality masks . . . anything except vaccines,” Eric Topol, founder and director of the Scripps Research Translational Institute, said in an email. “Which is wrong, since we need every tool in the kit to effectively take on delta; we’re not doing that well at all.”

5. What academia used to be like.  Before the internet, that is.

6. Jerry Brito on the coming regulatory challenge for crypto.

How many children are killed by the schools anyway?

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

Of course, with or without Covid, some number of children die at school. But it is surprisingly difficult to find out how many. In 2020, there were more than 50 million students in public elementary, middle or high schools, yet there is no systematic national database of student deaths at school. School shootings have claimed up to 75 deaths annually in recent years, and there are many other possible causes of death, such as traffic or sports accidents.

It’s entirely plausible that a few hundred students die each year for reasons directly related to school attendance. If suicides induced by school bullying but occurring off campus are included, the number could be higher still. Some 4,400 young people in America commit suicide in a typical year, and surely many of those deaths are attributable, at least partially, to events at school.

Adding up all these admittedly indirect chains of causation, it’s possible that school attendance leads to at least 2,000 deaths every year in the U.S. And those have nothing to do with Covid.

Fortunately, it is not customary in normal times to debate whether it is worth opening schools knowing that it could result in the death of perhaps 2,000 students. The true toll of opening schools is unknown, much less debated, and if there is a discussion it is over school shootings, which ought to be preventable (or at least limited) by measures other than closing schools.

This “head in the sand” approach is highly imperfect. Still, it is preferable to panicking and closing the schools every year.

It is difficult to calculate how many children have died of Covid, but perhaps the best estimate comes from England, where it caused 25 deaths of people younger than 18 in the year ended in March. The final tally is certainly higher in the more populous U.S., but as of July seven states still were reporting zero Covid deaths among children. This recent estimate suggests 358 deaths, though it is based on only 43 states.

Yes, it is worth considering whether school reopenings will lead to unacceptably high levels of Covid in the non-school population. It is also worth pointing out that Covid is spreading very rapidly in states with low vaccination rates — without the schools playing a role. In any case, it does not justify focusing solely on the safety of children in discussions of school reopening.

Economists have long studied the tendency of people to assign more value to a “known life” than to a “statistical life.” When a baby is trapped down a well, for example, many millions of dollars will be spent trying to save her. Her photo will appear on the evening news and on social media. Yet when it comes to saving lives in the aggregate, such as by installing more and better smoke detectors, there is only modest interest.

Right now too many Americans are trapped: Because the pandemic has been so dramatic for so many, every life looks like a known life rather than a statistical life. We all need to start working our way back to a bit more emotional distance.

Recommended.

The median voter theorem is underrated

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

More broadly, it is striking how many policies of the Biden administration reflect ideas or proposals from the Trump administration. Biden’s “Buy America” plan could be a Trump administration protectionist initiative. The Trump administration spent $2 trillion on coronavirus relief; the Biden administration proposed and spent $1.9 trillion. Trump wanted to pull U.S. troops out of Afghanistan; Biden actually did. Biden has left many of Trump’s anti-China policies, such as the tariffs, in place. Biden also has continued rapid deportation programs for immigrants.

All of these policies are broadly aimed at the center. It is no accident that Biden, even though his “honeymoon” period is ending, has remained broadly popular in the polls.

There are still areas in which Republicans and Democrats differ greatly, of course. On Covid-19, they have divergent attitudes and safety practices. Still, the Biden administration has not seriously considered either a nationwide vaccination mandate or governmental vaccine passports, as neither would be especially popular with voters.

Then there are cultural issues, where the median voter theorem most definitely does not hold. What seems to have happened is that Americans have picked one area in which they can let off steam and express their mutual mistrust — and in turn that has allowed a kind of consensus to form around many actual government policies. Perhaps what the median voter theorem misses is that individuals have a deeply irrational side and need to treat some political debates more like a mixed martial arts competition than as a forum for getting things done.

The median voter theorem tends to be unpopular in an increasingly left-leaning academic environment. It has a decidedly anti-utopian quality, as it insists that policy is not going to deviate too far from the views of the ordinary American. It implies that many projects of left-wing progressives are pipe dreams, at least until major shifts in public opinion set in. It dismisses the common progressive attitude that current voters would welcome major left-wing reforms and are only waiting for a heroic politician to stare down the special interest groups that oppose them.

To be clear, there is no presumption that the median voter actually wants the right thing. As an economist, I am particularly frustrated by how frequently American voters fail to appreciate the benefits of international trade and migration, or how they tend to believe that government programs financed by borrowing represent a free lunch. They also put disproportionate weight on low gasoline prices, to cite yet another example from a long list of mistaken views.

Still, as a practical matter, the median voter probably represents a kind of protection against the worst excesses and arrogances of the human spirit. Failed politicians do tend to get voted out of office. Crazy views, regardless of how popular they may be, tend to get sanded down by the political process.

The upshot, for the U.S. at least, is that the reality of American life is very different from the one that pundits regularly describe.

True.

Why has the Indian diaspora been so successful?

Dwarkesh writes to me:

Why do you think the Indian diaspora has been so successful? Just selection of the best immigrants from a large pool of candidates or something else too?

Yes, there are plenty of Indians, and surely that matters, but I see several others factors at work:

1. The Indian diaspora itself is large, estimated at 18 million and the single largest diaspora in the world.

2. A significant portion of the better-educated Indians are hooked into English-language networks early on, including through the internet.  The value of this connection has been rising due to the rising value of the internet itself.  That is a big reason to be bullish on the Indian diaspora.

3. India has been growing rapidly enough so that people understand the nature and value of progress, yet the country remains poor enough that further progress seems urgent.

4. Many Indian parents seem intent on expecting a great deal from their children.  The value of this cannot be overemphasized.  This effect seems to be stronger in India than in say Indonesia.

5. There is especially positive selection for Indians coming to America.  You can’t just run across a border, instead many of the ways of getting here involve some specialization in education and also technical abilities.  Virtually all migrated in legal manners, and here is some interesting data on how the various cohorts of Indians arriving in America differed by wave.

6. More speculatively, I see a kind of conceptual emphasis and also a mental flexibility resulting from India’s past as a mixing ground for many cultures.  Perhaps some of this comes from the nature of Hinduism as well, even for non-Hindu Indians (just as American Jews are somewhat “Protestant”).  Indians who move into leadership roles in U.S. companies seem to do quite well making a very significant cultural leap.  I cannot think of any other emerging economy where the same is true to a comparable extent.  In any case, the intellectual capital embedded in Indian culture is immense.

7. Those Indians who leave seem to retain strong ties to the home country, which in turn helps others with their subsequent upward mobility, whether in India or abroad.  In contrast, Russians who leave Russia seem to cut their ties to a higher degree.

8. I feel one of the hypotheses should involve caste, but I don’t have a ready claim at hand.

Here is the take of Stephen Manallack.  Here is Times of India.  (And by the way, here is Shruti’s piece on India’s 1991 reforms, not irrelevant to the diaspora.)

What else?

“The Crypto Revolution Will Not be Public”

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

In a remarkably honest yet radical speech last month about stablecoins, Fed Governor Randal Quarles argued that current payments systems already incorporate a great deal of information technology — and they are improving rapidly. The implication is that a central bank digital currency, or CBDC, is a solution in search of a problem.

Quarles also suggested that the Fed tolerate stablecoins, just as central banking has coexisted and indeed thrived with numerous other private-sector innovations. Stablecoins can serve as a private-sector experiment to see if individuals and institutions truly desire a radically different payments system, in this case based on crypto and blockchains. If they do, the system can evolve by having some but not all transactions shift toward stablecoin.

There need not be any “do or die” date of transition requiring a perfectly functioning CBDC. But insofar as those stablecoins can achieve the very simple methods of funds transfer outlined above, market participants will continue to use them more.

Quarles argued that with suitable but non-extraordinary regulation of stablecoin issuers, such a system could prove stable. He even seems to prefer the private-sector alternative: “It seems to me that there has been considerable private-sector innovation in the payments industry without a CBDC, and it is conceivable that a Fed CBDC, or even plans for one, might deter private-sector innovation by effectively ‘occupying the field.’”

In essence, Quarles is willing to tolerate a system in which privately issued dollar equivalents become a major means of consummating payments outside of the Fed’s traditional institutions. Presumably capital requirements would be used to ensure solvency.

For many onlookers, even hearing of innovation in finance raises worries about systemic risk. But perhaps the U.S. would do better by letting information technology advance than trying to shut it down. And if you are afraid of instability, are you really so keen to see foreign central bank digital currencies fill up this space?

If you are still skeptical, ask yourself two final questions. First, which has been more innovative on these issues: the private sector or the public sector? Second, how realistic are the prospects that Congress takes any effective action at all?

This is now a world in which radical monetary ideas are produced and consumed like potato chips. I say, pass the bag.

Recommended.

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.