Category: Current Affairs

My Caribbean podcast with the excellent Rasheed Griffith

One hour, fifteen minutes, almost all of it about the history and culture and economic future of the Caribbean, here is the audio.  It starts with Rasheed interviewing me, but later becomes more of a back-and-forth dialog, covering Cuba, Trinidad, Barbados, the best music from Jamaica, why Haiti has failed so badly, whether the Caribbean will be Latinized, and much more.  This one is pretty much entirely fresh material and I enjoyed doing it very much.

Rasheed is from Barbados, he is a very recent Emergent Ventures winner, and more generally his podcast focuses on the role of China in the Caribbean.  Newsletter and some prestigious podcast guests coming soon!

Here is Rasheed on Twitter.

A Majority of Doses are Now Second Doses

As of Feb. 18 (last day of full data) we gave out 817,708 second doses and just 702,426 first doses. In other words, a majority of doses are now second doses. As Daniel Bier writes this means that we are boosting some people from ~85% to ~95% protected when we could be vaccinating more first timers and getting them from 0% protected to ~85% protected.

If we followed the British rule and delayed the booster to 12 weeks, we could immediately more than *double* the number of people going from 0% protected to to ~85% protected. More first-doses would be great for the newly protected and more people at ~85% protection would also reduce transmission so there would be fewer new infections and less threat to the non-vaccinated.

The opportunity cost of not delaying the booster is measured in lives lost.

Texas utilities should have had more dynamic pricing

But there was also a missed opportunity on the demand side. Texas has retail choice for electricity, but the overwhelming majority of Texas customers face electricity prices that are too static, too inflexible, and don’t respond to market conditions. Economists have been advocating dynamic prices for decades, but adoption has been slow.

Case in point. While wholesale prices in the Texas market climbed last week to $9,000/MWh, the overwhelming majority of electricity customers in Texas continued to pay retail prices close to $120/MWh, barely 1/100th of the true marginal cost.

Not seeing these high prices, Texas consumers had little incentive to conserve. You had a feast or famine — with millions of consumers at an all-you-can-eat buffet — while millions of others faced tragic blackouts and, essentially, an infinite price.

If everyone instead had turned their thermostats to a chilly, but manageable, 65°, this could have really helped the state manage the emergency. As Severin Borenstein pointed out after the California power outages last August, even modest adjustments to the thermostat can save a lot of electricity.

Dynamic pricing allows customers to pay lower prices throughout 99% of the year, in exchange for facing much higher prices when supply is tight. Numerous studies have documented that dynamic pricing yields substantial demand reductions (here, here, here, and here).

You may have read about households who paid enormous electricity bills last week. 29,000 out of Texas’ 11+ million customers buy their electricity from Griddy, a retailer that charges customers wholesale prices for a monthly fee of $9.99/month. This is a very extreme version of dynamic pricing. The evidence shows that you don’t need such extreme price changes to encourage conservation. Moreover, it is straightforward to incorporate hedging into retail contracts to protect customers from these outcomes.

With 28GW of forced outages in Texas last week, it is unlikely that dynamic prices alone could have closed the gap between demand and supply. But dynamic pricing is the fastest and cheapest way to build flexibility into the market, and can play an important role moving forward.

Here is more from Lucas Davis.  Via Jonathan Carmel.

The AstraZeneca Vaccine Works Well

A new study looking at essentially the entirety of the Scottish population finds that both the Pfizer and AstraZeneca vaccine work very well at preventing hospitalizations from the first dose.

UK policy for use of vaccines against COVID-19 involves an offer of a first dose followed by a second dose 12 weeks later. To our knowledge, this is the first study of COVID-19 vaccine effect against hospitalisation for an entire nation after a single dose of vaccine. We found that a single dose of BNT162b2 COVID-19 vaccine was associated with a vaccine effect (VE) of 85% (95% CI 76 to 91) for COVID-19 hospitalisation 28-34 days post-vaccination. A single dose of ChAdOx1 vaccine was associated with a vaccine effect 94% (95% CI 73 to 99) at 28-34 days post-vaccination. VEs increased over time with a peak at 28-34 days post-vaccination for both vaccines. Comparable VEs were seen in those aged ≥80 years for prevention of COVID-19 hospitalisation with a high combined VE of 81% (95% CI 65 to 90) at 28-34 days post-vaccination.

Arne Akbar, president of the British Society for Immunology, noted “…overall these new findings should provide reassurance around the UK’s decision to offer the two doses of the vaccine 12 weeks apart.”

Another important point is that the AstraZeneca vaccine actually shows a higher effectiveness than the Pfizer vaccine. The study wasn’t designed to compare the vaccines and the populations getting the vaccines aren’t random samples. Nevertheless, the AstraZeneca vaccine appears to work well and it was actually given to a greater proportion of elderly patients.

The new results from Scotland support the UK, EU, and WHO decisions to authorize the AstraZeneca vaccine. If the US had authorized the AstraZeneca vaccine in late December at the same time as did the UK, millions more Americans could have been vaccinated saving many lives.

Where is the FDA’s cost-benefit calculation?

From the Comments, On FDF

Sure and Tom Meadowcroft have been hitting it out of the ballpark in the comments sections. Two examples.

Sure:

Protocol was made to serve man, not man to serve the protocol.

The reason we have protocols is because we need to weight the harms of waiting without a treatment against the harms that happen if the treatment is counterproductive in some unforeseen manner.

We can, normally, pretty easily measure the benefit side: count up the mortality and morbidity for the illness in question. The risk side is harder so we developed tests and processes to elucidate those: RCTs, literature reviews, regulatory oversight, mandatory waiting periods. At the end of the day though, the whole process is just one giant test to measure the likely harm of a new entity.

So when is a test worth doing? After all I do not order an MRI for every patient even though I could find a lot of early stage cancers that way.

..GSW to the abdomen with crashing bp with minimal response to volume? Straight to the OR. No matter the results of the CT scan they are still getting opened to stop the bleeding.

…So now we look at the vaccine approval process and methods to stretch doses. Pre-test probability that vaccines work? Inordinately high after passing Phase II. Odds that we hit on the precise optimal timing regimen on the first go? Nil.

The likelihood ratios for RCTs and approval mechanisms are powerful. But we are talking thousands of deaths per day. The odds that these tests will remotely alter management decisions is nil. It is malpractice to delay life saving treatment on tests exceedingly unlikely to change management decisions.

And remember the UK is not seeing horrid outcomes for doing this for a while now. A lot of theoretical failure mechanisms are now off the table.

Science is wholly about building a reliable model that accurately predicts future outcomes of current actions. While doing the actual experiment is the gold standard for knowledge acquisition, it is not the only option and in cases like this pandemic is not sufficiently better than past data to merit waiting.

As far as the regulators. I work with some of them directly. They are not overburdened to anywhere near the degree that the frontline clinicians have been hit. When I ask them to explain their cost benefit calculations, they have none. Not I cannot follow them. Not I disagree with them. They have done not an iota of math to justify their course of action.

Sorry, but I believe in evidence based medicine, not eminence based medicine. If you as a regulator cannot explain to me in technical terms the math behind your decision process, even if only back of the envelope, you are not worth putting in charge.

Approve all the vaccines, FDF, fractional dosing trials, and first dose followed by variolation trials should all be done now. It is was [what] the math demands.

Also this from Tom Meadowcroft:

Scientific researchers search for the truth. Medical clinicians use limited data balance cost and benefits in the face of uncertainty to save the most lives.

When searching for the truth, it is important to have high standards of statistical significance, integrity, and patience, because credibility and a reputation for integrity is everything. Every academic knows that a retracted paper or an accusation of playing fast and loose with statistics can be the death knell for a career. As a result it is prudent to be very certain before publishing. Public health officials, particularly those in charge of approving vaccines, dread the possibility that a vaccine that will be given to millions of healthy people, often children, to prevent diseases where death is rare, which could harbor some flaw that causes a hundred avoidable deaths; they seek the highest standards of proof of safety and efficacy before approving such a vaccine.

But a pandemic is not a search for truth, and a COVID vaccine administered in the midst of a pandemic is very different than a measles vaccine administered to 2-year-olds. The pandemic makes these decisions for FDF or for vaccine approvals into clinical decisions, where health professionals should be balancing the certain benefit of reducing the thousands of daily deaths against the uncertain cost of the possibilities of harmful side-effects and uncertain details of efficacy (when does immunity kick in, how long does it last, how valuable is a booster) that additional months of testing and trials would reveal more clearly.

Public health researchers, academics for the most part, lack the ability (and courage) to make the sort of cost/benefit analysis with necessarily limited data that clinical physicians make every day in examination rooms. Any good clinician, faced with the citizenry of a country as their patient, would have opted for FDF, the AZ vaccine, and quite likely reduced doses by the start of the year. Because we are stuck with academics and administrators as our decision makes, unable to see beyond their usual routine of searching for the truth and protecting their reputations, thousands more will die.

Venezuelan relative price fact of the day

As Venezuela enters its eighth year of economic crisis, a deeply personal drama is playing out inside the home: Millions of women are no longer able to find or afford birth control, pushing many into unplanned pregnancies at a time when they can barely feed the children they already have.

Around Caracas, the capital, a pack of three condoms costs $4.40 — three times Venezuela’s monthly minimum wage of $1.50.

Birth control pills cost more than twice as much, roughly $11 a month, while an IUD, or intrauterine device, can cost more than $40 — more than 25 times the minimum wage. And that does not include a doctor’s fee to have the device put in.

Here is the full NYT article.

The First Dose is Good

WSJ: The Covid-19 vaccine developed by Pfizer Inc. and BioNTech SE generates robust immunity after one dose and can be stored in ordinary freezers instead of at ultracold temperatures, according to new research and data released by the companies.

The findings provide strong arguments in favor of delaying the second dose of the two-shot vaccine, as the U.K. has done . They could also have substantial implications on vaccine policy and distribution around the world, simplifying the logistics of distributing the vaccine.

A single shot of the vaccine is 85% effective in preventing symptomatic disease 15 to 28 days after being administered, according to a peer-reviewed study conducted by the Israeli government-owned Sheba Medical Center and published in the Lancet medical journal. Pfizer and BioNTech recommend that a second dose is administered 21 days after the first.

The finding is a vindication of the approach taken by the U.K. government to delay a second dose by up to 12 weeks so it could use limited supplies to deliver a single dose to more people, and could encourage others to follow suit. Almost one-third of the U.K.’s adult population has now received at least one vaccine shot. Other authorities in parts of Canada and Europe have prioritized an initial shot, hoping they will have enough doses for a booster when needed.

Preliminary data also suggest that the other widely used vaccine in the U.K. developed by AstraZeneca PLC and the University of Oxford could have a substantial effect after a first dose .

The Israeli findings came from the first real-world data about the effect of the vaccine gathered outside of clinical trials in one of the leading nations in immunization against the coronavirus. Israel has given the first shot to 4.2 million people—more than two-thirds of eligible citizens over 16 years old—and a second shot to 2.8 million, according to its health ministry. The country has around 9.3 million citizens.

…”This groundbreaking research supports the British government’s decision to begin inoculating its citizens with a single dose of the vaccine,” said Arnon Afek, Sheba’s deputy director general.

The Israeli study is here. Data from Quebec also show that a single dose is highly effective, 80% or higher (Figure 3) in real world settings.

It’s becoming clearer that delaying the second dose is the right strategy but it was the right strategy back in December when I first started advocating for First Doses First. Waiting for more data isn’t “science,” it’s sometimes an excuse for an unscientific status-quo bias.

Approximately 16 million second doses have been administered in the US. If those doses had been first doses an additional 16 million people would have been protected from dying. Corey White estimates that every 4000 flu vaccinations saves a life which implies 4000 lives would have been saved by going to FDF. COVID, of course, is much deadlier than the flu–ten times as deadly or more going by national death figures (so including transmission and case fatality rate)– so 40,000 deaths is back of the envelope. Let’s do some more back-of-the-envelope calculations. Since Dec. 14, there have been approximately 10 million confirmed cases in the United States and 200,000 deaths. There are 200 million adults in the US so 1/1000 adults has died from COVID, just since Dec. 14. If we use 1/1000 as the risks of a random adult dying from COVID, then an additional 16 million vaccinations would have saved 16,000 lives. But that too is likely to be an underestimate since the people being vaccinated are not a random sample of adults but rather adults with a much higher risk of dying from COVID. Two to four times that number would not be unreasonable so an additional 16 million vaccinations might have avoided 32,000-64,000 deaths. Moreover, an additional 16 million first doses would have reduced transmission. None of these calculations is very good but they give a ballpark.

It is excellent news that the vaccine is stable for some time using ordinary refrigeration. Scott Duke Kominers and I argue that there is lot of unused vaccination capacity at the pharmacies and reducing the cold storage requirement will help to bring that unused capacity online. The announcement is also important for a less well understood reason. If Pfizer is only now learning that ultra-cold storage isn’t necessary then we should be looking much more closely at fractional dosing.

When I said that we should delay the second dose, people would respond with “but the companies say 21 days and 28 days! Listen to the science!”. That’s not scientific thinking but magical thinking. Listening to the science was understanding that the clinical trial regimen was designed at speed with the sole purpose of getting the vaccines approved. The clinical trial was not designed to discover the optimal regimen for public health. Don’t get me wrong. Pfizer and Moderna did the right thing! But it was wrong to think that the public health authorities could simply rely on “the science” as if it were written on stone. Even cold-storage wasn’t written on stone!  Now that the public health authorities know that the clinical trial regimen isn’t written in stone they should be more willing to consider policies such as delaying the second dose and fractional dosing.

We are nearing the end in the US but delaying the second dose and other dose-stretching policies are going to be important in other countries.

British real wealth is rising

Sterling climbed to $1.40 for the first time in almost three years as investors looked past gloomy data and instead focused on hopes the country’s rapid coronavirus vaccine rollout will boost economic prospects.

The currency has risen 2.4 per cent against the dollar since the end of 2020, and more than 3 per cent against the euro. It traded as high as $1.4008 and €1.156, respectively, on Friday.

Here is more from the FT.

Myopic Voters and Natural Disaster Policy

Do voters effectively hold elected officials accountable for policy decisions? Using data on natural disasters, government spending, and election returns, we show that voters reward the incumbent presidential party for delivering disaster relief spending, but not for investing in disaster preparedness spending. These inconsistencies distort the incentives of public officials, leading the government to underinvest in disaster preparedness, thereby causing substantial public welfare losses. We estimate that $1 spent on preparedness is worth about $15 in terms of the future damage it mitigates. By estimating both the determinants of policy decisions and the consequences of those policies, we provide more complete evidence about citizen competence and government accountability.

From the now classic paper of the same title by Andrew Healy and Neil Malhotra. As Neil said on twitter It becomes depressing tweeting out this article after every instance of government failure,” but there you go.

Canada and First Doses First

…With such a highly protective first dose, the benefits derived from a scarce supply of vaccine could be maximized by deferring second doses until all priority group members are offered at least one dose. There may be uncertainty about the duration of protection with a single dose, but the administration of a second dose within 1 month after the first, as recommended, provides little added benefit in the short term, while high-risk persons who could have received a first dose with that vaccine supply are left completely unprotected. Given the current vaccine shortage, postponement of the second dose is a matter of national security that, if ignored, will certainly result in thousands of Covid-19–related hospitalizations and deaths this winter in the United States — hospitalizations and deaths that would have been prevented with a first dose of vaccine.

Danuta M. Skowronski, M.D.
British Columbia Centre for Disease Control, Vancouver, BC, Canada

Gaston De Serres, M.D., Ph.D.
Institut National de Santé Publique du Québec, Quebec City, QC, Canada

That’s from a letter to the NEJM which also includes a debate on delaying the second dose and a poll (vote for delaying the second dose!). What I want to point out today is that the authors are experts from Canada. I believe that first doses first will save lives in the US but delaying the second dose and other dose-stretching policies are even more vital in countries where vaccines supplies are more limited than in the United States.

Canada and Novavax

Canada has made some smart moves with the Novavax vaccine. First, they initiated a rolling review of the Novavax vaccine in late January which suggests that they might authorize the vaccine based on the British trial before the US trial is concluded. The FDA will probably wait until the US trial is concluded. Second, Canada also signed a production agreement to bring some capacity online in Canada, although that will take time. That agreement, however, is on top of an advance purchase of 52 million doses with an option on another 24 million doses.

In short, if they act quickly, Canada could approve the Novavax vaccine before the United States and get a jump on its own vaccination efforts.

The regulatory state and the passage of time

The mere passage of time as an explanatory factor is underrated in public choice and regulatory economics, though Mancur Olson understood it well.  Here is an update on the new CDC guidelines for school reopening:

For months, President Biden has been urging schools to reopen, and promised that guidelines from the Centers for Disease Control and Prevention would help them do so safely.

At the same time, public health experts including some at the CDC said available evidence suggested schools could safely open as long as precautions were in place. That raised expectations that the nation’s K-12 education system might accelerate its return to in-person learning.

But the much-anticipated guidelines released Friday were, in fact, more measured than some expected, with full in-person schooling recommended only when levels of community transmission are quite low, a standard that almost no place in the U.S. meets today.

Here is the full article.  The American Federation of Teachers is happy, but six feet between all students for virtually all districts is a non-starter.  No matter what you think of the substance of the school reopening issue, it takes only a modicum of sense to realize if you tell people that six feet of distance is needed, in essence you are saying that a safe reopening is impossible altogether.  Here is the rant of a “progressive” parent.

You will notice that these regulatory factors are another reason why the speed premium during a pandemic is so high — if you wait too long to fix the core problem, the regulators, slow though they may be, will encumber just about everything.

Half Doses of Moderna Produce Neutralizing Antibodies

A new phase II study from Moderna shows that half-doses (50 μg) appear to be as good as full doses (100 ug) at generating correlates of protection such as neutralizing antibodies.

In this randomized, controlled phase 2 trial, the SARS-CoV-2 vaccine candidate mRNA-1273, administered as a two-dose vaccination regimen at 50 and 100 μg, exhibited robust immune responses and an acceptable safety profile in healthy adults aged 18 years and older. Local and systemic adverse reactions were mostly mild-to-moderate in severity, were ≤4 days of median duration and were less commonly reported in older compared with younger adults. Anti-SARS-CoV-2 spike binding and neutralizing antibodies were induced by both doses of mRNA-1273 within 28 days after the first vaccination, and rose substantially to peak titers by 14 days after the second vaccination, exceeding levels of convalescent sera from COVID-19 patients. The antibodies remained elevated through the last time point assessed at 57 days. Neutralizing responses met criteria for seroconversion within 28 days after the first vaccination in the majority of participants, with rates of 100% observed at 14 and 28 days after the second vaccination. While no formal statistical testing was done, binding and neutralizing antibody responses were generally comparable in participants who received the 100 μg mRNA-1273 and the 50 μg dose at all time points and across both age groups. Overall, the results of this randomized, placebo-controlled trial extend previous immunogenicity and safety results for mRNA-1273 in the phase 1 study in an expanded cohort including participants older than 55 years of age [16, 19].

[These data] confirm that a robust immune response is generated at both 50 and 100 ug dose levels.

As I wrote earlier, halving the dose is equivalent to instantly doubling the output of every Moderna factory.

See my piece in the Washington Post on getting to V-day sooner for an overview of dose stretching strategies.

Addendum: France says one dose is sufficient for previously COVID infected.

The Big Push: A Plan to Accelerate V-Day

In the Washington Post I have an extensive piece on accelerating progress to V-day, Vaccine or Victory day, the day everyone who wants a vaccine has gotten one. I cover themes that will be familiar to MR readers, including First Doses First, Fractional Dosing, Approving More Vaccines and DePrioritization to Expand Delivery. I won’t belabor these points here but the piece is useful at collecting all the arguments in one place and there are lots of authoritative links.

One point I do want to make is that all the pieces of the “Tabarrok plan,” if  you will, fit together. Namely, use First Doses First to make a big push to get as many people vaccinated with first doses as possible in the next 90 days. Approve more vaccines including Johnson & Johnson, AstraZeneca and others and make them available to anyone, anywhere–that is possible because these vaccines don’t require significant cold storage, J&J is a single shot and AZ is better with a second shot at 12 weeks or later all of which eases distribution.

…some people argue that adding a third (or fourth) vaccine might not help because of persistent delivery logjams at the state and local levels. But we know there is unused distributional capacity, even for the supply we do have. The United States is currently administering about 1.5 million coronavirus vaccine shots per day. While that sounds like a lot, for comparison consider that in September — during the pandemic, when social distancing measures were in full effect — we vaccinated for the seasonal flu in some weeks at the rate of 3 million people a day.

There are two main reasons the rollout has been so slow. First, the Moderna and especially the Pfizer vaccines require ultracold storage. (The Johnson & Johnson and AstraZeneca doses can be stored at ordinary refrigerator temperatures.) Second, we have tried to prioritize vaccinations using a confusing mishmash of age, health conditions and essential-worker status that differs by state and sometimes even by county. “Confirming such criteria is complicated at best, and it’s probably not even feasible to try under conditions of duress,” as Baylor’s Hotez puts it.

Arguments continue about prioritization lists, and the idea of tossing them entirely would cause a political fight. But there is a compromise at hand: Quickly approve the Johnson & Johnson and AstraZeneca vaccines and make them — and only them — available to anyone, anywhere. Keeping things simple is a sure way to increase total vaccinations. With no cold-storage requirement, the new vaccines could be administered by any of the 300,000 pharmacists and more than 1 million physicians in the United States authorized to deliver vaccines, most of whom are not now giving Pfizer or Moderna shots.