Category: Medicine

Vaccine incentives matter (from my email)

I am a physician in private practice in [redacted]. We have just been approved to order and administer the vaccine to tier-appropriate patients. Medicare has approved a payment of 18$ for the first shot and 28$ for the second. As far as we can determine we will not be allowed to bill for an office visit so that is the entire amount we will receive for registering the patients, screening then for covid outside of the office, taking their vital signs, taking a history to see if there are any contraindications to the vaccine, administering the vaccine, observing them in the clinic for a minimum of 15 minutes up to 30 minutes depending on their history, and recalling them in 28 days and going through most of the same procedure again, minus the registration and history. There is also an extensive regime of recording and reporting all vaccination data daily to the state government. We had anticipated hiring someone to manage this new service due to the amount of new work that is required. At this rate we might be able to give 10 shots an hour in each of our 3 clinics if we see no other patients for illness, injury, or covid testing.

Do I need to say that we cannot possibly afford to do this for the reimbursement offered. The alternative is for patients to receive the vaccine in some state funded site or clinic. That may take a very long time to roll out.

We need many more economists complaining about this, right?  Other than John Cochrane, where will we find them? Why do we not find them?

Dr. Fauci, Straussian

Recently, a figure to whom millions of Americans look for guidance — Dr. Anthony S. Fauci, an adviser to both the Trump administration and the incoming Biden administration — has begun incrementally raising his herd-immunity estimate.

In the pandemic’s early days, Dr. Fauci tended to cite the same 60 to 70 percent estimate that most experts did. About a month ago, he began saying “70, 75 percent” in television interviews. And last week, in an interview with CNBC News, he said “75, 80, 85 percent” and “75 to 80-plus percent.”

In a telephone interview the next day, Dr. Fauci acknowledged that he had slowly but deliberately been moving the goal posts. He is doing so, he said, partly based on new science, and partly on his gut feeling that the country is finally ready to hear what he really thinks.

Hard as it may be to hear, he said, he believes that it may take close to 90 percent immunity to bring the virus to a halt — almost as much as is needed to stop a measles outbreak.

Asked about Dr. Fauci’s conclusions, prominent epidemiologists said that he might be proven right…

Dr. Fauci said that weeks ago, he had hesitated to publicly raise his estimate because many Americans seemed hesitant about vaccines, which they would need to accept almost universally in order for the country to achieve herd immunity.

Here is the full NYT story.  A few points:

1. Surely Straussianism by now should be persuasive as a general theory.

2. Fauci is idolized by many as a kind of anti-Trump, but he is a terrible risk communicator, as evidenced also by his recent attacks on some of the “lesser” vaccines (which still would work if applied collectively).  Not to mention his earlier remarks on masks, and also the mid-March safety of cruises.  How a person understands Fauci is in fact a pretty good litmus test.

3. Should you be trusting everything the insiders are telling you about FDA processes?

4. I genuinely do not know what the herd immunity threshold is, but I assure you I am trying to tell you the truth on this one (and other matters).  My Straussianism is not a normative theory of my own communication, but rather a positive theory of how the world works, and it has been vindicated once again.

New blood-test device monitors blood chemistry continually

“A blood test is great, but it can’t tell you, for example, whether insulin or glucose levels are increasing or decreasing in a patient,” said Tom Soh, a professor of electrical engineering and of radiology at Stanford. “Knowing the direction of change is important.”

Now, Soh, in collaboration with Eric Appel, an assistant professor of materials science and engineering, and colleagues have developed a technology that can provide this crucial piece of missing information. Their device, which they’ve dubbed the “Real-time ELISA,” is able to perform many blood tests very quickly and then stitch the individual results together to enable continuous, real-time monitoring of a patient’s blood chemistry. Instead of a snapshot, the researchers end up with something more like a movie.

In a new study, published in the journal Nature Biomedical Engineering, the researchers used the device to simultaneously detect insulin and glucose levels in living diabetic laboratory rats. But the researchers say their tool is capable of so much more because it can be easily modified to monitor virtually any protein or disease biomarker of interest…

Technologically, the system relies upon an existing technology called Enzyme-linked Immunosorbent Assay – ELISA (“ee-LYZ-ah”) for short. ELISA has been the “gold standard” of biomolecular detection since the early 1970s and can identify virtually any peptide, protein, antibody or hormone in the blood. An ELISA assay is good at identifying allergies, for instance. It is also used to spot viruses like HIV, West Nile and the SARS-CoV-2 coronavirus that causes COVID-19.

“We do ELISA continuously,” Soh said.

The Real-time ELISA is essentially an entire lab within a chip with tiny pipes and valves no wider than a human hair. An intravenous needle directs blood from the patient into the device’s tiny circuits where ELISA is performed over and over.

Here is the full story, via Malinga Fernando.

The Tony Blair “one dose” idea

Here is the source, of course Alex Tabarrok was there first.  For now give everyone one dose rather than two, and enjoy the partial but more broadly spread protection.  Here are the reactions from two epidemiologists:

Professor Wendy Barclay, from the department of infectious disease at Imperial College London, said Mr Blair’s idea was interesting but agreed it was “too risky” to try without further evidence.

And Professor Neil Ferguson, also from Imperial, added that the UK regulator had authorised the vaccine on the basis that people would receive two doses.

Administering one dose only would require “an entirely different regulatory submission”, he told a Commons committee.

A Department of Health and Social Care spokesperson said: “Over the coming weeks and months, the rate of vaccinations will increase as more doses become available and the programme continues to expand.”

Where are their cost-benefit analyses?  Letting people get infected at current and indeed accelerating rates is also “too risky,” yes?  Is there an epidemiologist or public health expert out there willing to show his or her work, either for or against this idea?  A genuine query, and of course comments are open.  How about one dose for Moderna only?  If we are to defer to their expertise, they do actually have to step up and be the experts, right?

Update on the new Covid-19 strain

Here is a very good article with many points, here are two in particular that caught my attention:

People with a weakened immune system may give the virus this opportunity, as Gupta’s data show. More evidence comes from a paper published in The New England Journal of Medicine on 3 December that described an immunocompromised patient in Boston infected with SARS-CoV-2 for 154 days before he died. Again, the researchers found several mutations, including N501Y. “It suggests that you can get relatively large numbers of mutations happening over a relatively short period of time within an individual patient,” says William Hanage of the Harvard T.H. Chan School of Public Health, one of the authors. (In patients who are infected for a few days and then clear the virus, there simply is not enough time for this, he says.) When such patients are given antibody treatments for COVID-19 late in their disease course, there may already be so many variants present that one of them is resistant, Goldstein says.

And:

These could impact the binding of the virus to human cells and also its recognition by the immune system, Farrar says. “These South African mutations I think are more worrying than the constellation of the British variant.” South African hospitals are already struggling, he adds. “We’ve always asked, ‘Why has sub-Saharan Africa escaped the pandemic to date?” Answers have focused on the relative youth of the population and the climate. “Maybe if you just increase transmission a bit, that is enough to get over these factors,” Farrar says.

Developing…the speed premium of course is rising…

School Closures During the 1918 Flu Pandemic

The COVID-19 pandemic has reignited interest in responses to the 1918-19 influenza pandemic, the last comparable U.S. public health emergency. During both pandemics, many state and local governments made the controversial decision to close schools. We study the short- and long-run effects of 1918-19 pandemic-related school closures on children. We find precise null effects of school closures in 1918 on school attendance in 1919-20 using newly collected data on the exact timing of school closures for 168 cities in 1918-19. Linking affected children to their adult outcomes in the 1940 census, we also find precise null effects of school closures on adult educational attainment, wage income, non-wage income, and hours worked in 1940. Our results are not inconsistent with an emerging literature that finds negative short-run effects of COVID-19-related school closures on learning. The situation in 1918 was starkly different from today: (1) schools closed in 1918 for many fewer days on average, (2) the 1918 virus was much deadlier to young adults and children, boosting absenteeism even in schools that stayed open, and (3) the lack of effective remote learning platforms in 1918 may have reduced the scope for school closures to increase socioeconomic inequality.

That is from a new paper by Philipp Ager, Katherine Eriksson, Ezra Karger, Peter Nencka, and Melissa A. Thompson.  This is very good and important work, though you will find some Denkfehler in the second half of the abstract, namely confusing short- and long-run (is it so appalling to consider that “school” isn’t always “useful learning” over a 20-year time horizon?) and confusing inequality with absolute performance.  Those are simple points people, you are being misled by your ideology.

First Dose First

Writing on twitter Keith Klugman, world expert on infectious diseases and director of the Gates Foundation Pneumonia program, supports a policy I have argued for–First Doses First.

First doses of Pfizer/Moderna vaccines are 90%+ effective after 14 days. Most high risk lives will be saved by giving all these limited early supplies of vaccine as first doses – second doses can be given later if first dose effectiveness wanes or when supply improves

Here’s a way of thinking about this policy. Suppose you are scheduled for your second dose of the Pfizer or Moderna vaccine but you have the option of giving your second dose to your spouse as their first dose. Would you?

If the answer is yes then can you ethically deny this to someone else’s spouse?

Keep in mind that we have at least three more vaccines that could be available in as little as 12 weeks, Astra-Zeneca, Johnson & Jonson and Novavax. We are also pushing for more doses from Pfizer and we should be willing to pay top-dollar for those doses. As those vaccines come online we can deliver second doses.

Addendum: If you are 75 and your spouse is 25 then maybe you wouldn’t give your second dose to your spouse and that too ought to help us think about the larger questions of allocation.

The Tremendous Success of Operation Warp Speed

I am annoyed at Fauci for the second time, this time for dissing the AZ vaccine:

But even if the vaccine ends up being approved, it will probably only have an efficacy of 60 to 70 percent. “What are you going to do with the 70 percent when you’ve got two (vaccines) that are 95 percent? Who are you going to give a vaccine like that to?” Anthony Fauci, the leading American expert on vaccines, recently wondered.

This attitude is counter-productive. As I wrote earlier:

In the big picture, the efficacious of a vaccine doesn’t matter per se what matters is getting to herd immunity. If you have a less efficacious vaccine you need to vaccinate more people but herd immunity is herd immunity, i.e. vaccines mostly protect people not because they are efficacious but because we reach herd immunity.

As a result, it can be much better to start vaccinating now with a 70% efficacious vaccine than wait for a 95% efficacious vaccine–thus, we need to encourage early vaccination. Indeed the AZ vaccine ought to be approved immediately (I predict the UK will approve by next week) and be made available to anyone who doesn’t want to wait for another vaccine.

For the next year or two, we will be operating under conditions of scarcity and we need to use every tool at our disposal. A 70% effective vaccine is great, well above what the FDA required and better than the flu vaccine. If you live in a country in which everyone has been vaccinated you won’t give a damn whether they were vaccinated with a 95% effective vaccine or a 70% effective vaccine–both will give you nearly 100% safety and allow life to return to normal.

The new Covid strain and its policy implications

Here is one account, please note this investigation is in its early days:

“An increase in R of 0.4 or greater is extremely bad news. During the national lockdown in November the best we could achieve was an R value of somewhere between 0.8 and 1.0 around the UK,” said Prof Hunter. “What this means is that even if we went back to the lockdown it would still not be enough to bring the R value down to less than 1.0.”

Note also it is very likely the new mutation already has spread well beyond the UK.  And with compounding, an R increase of 0.4 is really bad as time passes.

If this all is true, what are the policy implications?  First, a lockdown with no pending vaccine will only postpone problems, a’ la the herd immunity theorists.

Second, we do have vaccines and so in any plausible model faster viral spread implies a faster timetable for vaccine approval and distribution.  And it implies we should have been faster to begin with.

If you used to say “we were just slow enough,” you now have to revise that opinion and believe that greater speed is called for, both prospectively and looking backwards.

In any plausible model.

If Godzilla is faster than you had thought, you need to start running away sooner.  And you needed to have started running away sooner.  In any plausible model.

In any plausible model.

Yet somehow I do not expect the rooftops to be so crowded over the next few days.

What should I ask Patricia Fara?

I will be doing a Conversation with her, here is part of her Wikipedia page:

Patricia Fara is a historian of science at the University of Cambridge. She is a graduate of the University of Oxford and did her PhD at the University of London

Her areas of particular academic interest include the role of portraiture and art in the history of science, science in the 18th century England during the Enlightenment and the role of women in science. She has written about numerous women in science, mathematics, engineering, and medicine including: Hertha AyrtonLady Helen GleichenMona Chalmers WatsonHelen Gwynne-VaughanIsabel Emslie HuttonFlora MurrayIda MacleanMarie Stopes, and Martha Annie Whiteley. She has argued for expanded access to childcare as a means of increasing the retention of women in science. She has written and co-authored a number of books for children on science. Fara is also a reviewer of books on history of science. She has written the award-winning Science: A Four Thousand Year History (2009) [and Erasmus Darwin: Sex, Science, and Serendipity (2012). Her most recent book is A Lab of One’s Own: Science and Suffrage in the First World War” (2017). In 2013, Fara published an article in Nature (journal), stressing the fact that biographies of female scientists perpetuate stereotypes.

And she has a new book coming out on Isaac Newton.  So what should I ask her?

Rapid Antigen Tests in Canada

Josh Gans announces a program of Rapid Antigen Tests in Canada backed by a consortium of major Canadian companies.

Big News! Today I am very pleased to be able to reveal to the world something that I have been very proud to have been working on with a hundred or so other people: The CDL Rapid Screening Consortium. Led by our Creative Destruction Lab, this consortium is a group of 12 companies who are partnering with Health Canada to begin the roll-out of rapid antigen screens to be a part of daily life for the next 12-18 months and deliver a safer path to normality. We have been working since September intensively to put the consortium together, explore screening options that were available globally and come up with protocols and an evolving standard operating procedure (SOP) to bring rapid antigen screens at scale to economies all around the world. The goal is to solve the pandemic information gap and ensure that we can quickly identify and isolate infectious people and protect others.

The initial sites will be run by RSC members. Those members are Air Canada, Rogers, Loblaws, Shoppers Drug Mart, Magna, Nutrien, Suncor, Genpact, Scotiabank, MDA, CPPIB and MLSE.

Read Josh’s announcement for more details and here is the website for the CDL Rapid Screening Consortium.

Down Syndrome and Covid

Among groups at higher risk of dying from COVID-19, such as people with diabetes, people with DS stand out: If infected, they are five times more likely to be hospitalized and 10 times more likely to die than the general population, according to a large U.K. study published in October. Other recent studies back up the high risk.

Researchers suspect background immune abnormalities, combined with extra copies of key genes in people with DS—who have three copies of chromosome 21 rather than the usual two—make them more vulnerable to severe COVID-19. “This is a vulnerable population that may need protective policies put in place,” says Julia Hippisley-Cox, a clinical epidemiologist at the University of Oxford’s medical school and senior author on the U.K. study.

On 2 December, the United Kingdom’s Joint Committee on Vaccination and Immunisation recommended prioritizing people with DS for speedy vaccination. But the more than 200,000 Americans with DS so far are not slated for early vaccination. Nor has the U.S. Centers for Disease Control and Prevention (CDC) included DS in its list of conditions it says boost the risk for severe COVID-19.

Here is the article, surely this merits further discussion as we allocate vaccines?  And note this higher mortality risk holds even after controlling for other factors, such as living in group homes.  And here you will find the original study.

Double the Inoculated Population with One Dose

I’ve been arguing that we should delay the second dose (or at least not hold back first doses) in order to hit the virus hard and inoculate more people on the first dose. I wrote:

We should vaccinate 6 million people with first dose NOW. It is deadly cautious to hold second dose in *reserve*. Supply chain will be ok and the exact timing of the second dose is not magical and likely not critical. In the accidental low-dose, standard-dose regime for the AZ vaccine, people got the second dose 7 to 8 weeks after the first dose and that was the 90% efficacious regime. [A different vaccine obviously but ] Exact timing of the second-dose does not seem critical, although everyone should get a second dose.

Today epidemiologist Michael Mina and writer Zeynep Tufekci, who has been ahead of the curve on much of the discussion, make the case even more strongly in the NYTimes:

First, the science. While the vaccine trials were designed to evaluate a two-dose regimen, some immunity might be acquired before a second dose is administered. We know, for instance, that a Covid-19 infection appears to yield protection for at least six months. While infections are not vaccinations, and while we need more data on this, it’s plausible that the immunity gained from a vaccination may turn out to be even stronger than what comes from an infection. The reason we do a second — booster — vaccination is that these later doses help to solidify immune memory, in part by giving extra training to the cells that produce antibodies, a process called affinity maturation. But this process begins with the single dose, and the evidence collected between the time of the first and second doses in tens of thousands of people in the Phase 3 trials suggests that the level of affinity maturation may provide enough protection to meet the standards we have set for vaccine approval during this pandemic even without the second dose.

While we know that the single dose can protect against disease, we don’t yet know how long this immune protection will last, and at what level. However, there is no rule that says that vaccines must be boosted within weeks of each other. For measles, the booster dose is given years after the first dose. If the booster dose could be given six months or a year after the first dose, while maintaining high efficacy before the second dose, that would allow twice as many people to get vaccinated between now and later next year, accelerating herd immunity — greatly helping end the crisis phase of the pandemic in the United States.

… we should begin immediate single-dose trials, recruiting volunteers from low-risk populations who are first in line for the vaccinations. For example, among health care workers protective equipment works, rates of infection among this group have fallen sharply and severe disease is much more rare.Younger essential workers without risk factors are less likely to be severely affected if they are exposed since this disease’s impact rises steeply with age. Just as tens of thousands of people volunteered for the earlier vaccine trials, many may well volunteer to test a placebo against a second dose, allowing us to quickly ascertain questions of durability and effectiveness of the single dose.

Two additional points. First, mix and match, as I argued earlier, may be beneficial:

…we could mix and match vaccines. The UK will run a trial on this question. Mix and matching has two potentially good properties. First, mix and matching could make the immune system response stronger than either vaccine alone because different vaccines stimulate the immune system in different ways. Second, it could help with distribution. It’s going to be easier to scale up the AZ vaccine than the mRNA vaccines, so if we can use both widely we can get more bang for our shot.

Second, an economics issue. If we want Pfizer and Moderna on board we need to pay them not just to run the clinical trials but to be happy with potentially selling half as many doses. Incentives matter.

Covid-19 is also not so great for young people

Young adults are dying at historic rates. In research published on Wednesday in the Journal of the American Medical Association, we found that among U.S. adults ages 25 to 44, from March through the end of July, there were almost 12,000 more deaths than were expected based on historical norms.

In fact, July appears to have been the deadliest month among this age group in modern American history. Over the past 20 years, an average of 11,000 young American adults died each July. This year that number swelled to over 16,000.

The trends continued this fall. Based on prior trends, around 154,000 in this demographic had been projected to die in 2020. We surpassed that total in mid-November. Even if death rates suddenly return to normal in December — and we know they have not — we would anticipate well over 170,000 deaths among U.S. adults in this demographic by the end of 2020.

That is from Jeremy Samuel Faust, Harlan M. Krumholz and at the NYT.  To be clear, this is not the main problem, but it is not a nothingburger either.  3,656 deaths per day right now, no matter what the ages how many other American catastrophes can rival that?  #1 cause of death in the country right now, bar none.