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Movement data from last weekend show Melburnians engaging in what experts have called thousands of small transgressions with the potential to drive COVID-19 infections higher, as the effect of 200 days of lockdown takes an emotional toll.
Google mobility data compiled by The Age reveals that across the state last Friday and Saturday, people were moving more than at any time since mid-July last year when complacency prompted Premier Daniel Andrews to plunge the state into stage-four lockdown and mandatory mask-wearing.
Last weekend saw a spate of breaches including an organised takeaway pub crawl in Richmond and an engagement party in Caulfield North attended by 69 guests. The couple involved in the illegal party have received $5400 fines. Two of their parents were also fined and other guests are being interviewed.
Some metropolitan municipalities including Glen Eira and Bayside recorded their highest lockdown movement levels last week, ahead of a number of mystery cases appearing in St Kilda.
Professor Mike Toole from Melbourne’s Burnet Institute, who lives in a mobility hotspot in the inner south, said he was shocked to witness large groups of people gathering in parks at the weekend.
Walmart, Target and Lowe’s, by contrast, all lifted sales forecasts this week after beating expectations for the three months to the end of July. While demand for toilet paper and cleaning supplies has cooled after 2020s pantry hoarding, the appetite for other products was broad-based. Party supplies, apparel and travel gear flew off Walmart’s shelves. At Home Depot, an early cache of Halloween decorations sold out almost immediately. Swimsuits and children’s clothing were similarly popular at Target and, in another sign of confidence, more customers returned to Walmart and Target store aisles after a year of browsing online.
Here is the associated FT article. Which set of values do you prefer? Which do most people prefer?
Today we are releasing a new paper on dose-stretching, co-authored by Witold Wiecek, Amrita Ahuja, Michael Kremer, Alexandre Simoes Gomes, Christopher M. Snyder, Brandon Joel Tan and myself.
The paper makes three big points. First, Khoury et al (2021) just published a paper in Nature which shows that “Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection.” What that means is that there is a strong relationship between immunogenicity data that we can easily measure with a blood test and the efficacy rate that it takes hundreds of millions of dollars and many months of time to measure in a clinical trial. Thus, future vaccines may not have to go through lengthy clinical trials (which may even be made impossible as infections rates decline) but can instead rely on these correlates of immunity.
Here is where fractional dosing comes in. We supplement the key figure from Khoury et al.’s paper to show that fractional doses of the Moderna and Pfizer vaccines have neutralizing antibody levels (as measured in the early phase I and phase II trials) that look to be on par with those of many approved vaccines. Indeed, a one-half or one-quarter dose of the Moderna or Pfizer vaccine is predicted to be more effective than the standard dose of some of the other vaccines like the AstraZeneca, J&J or Sinopharm vaccines, assuming the same relationship as in Khoury et al. holds. The point is not that these other vaccines aren’t good–they are great! The point is that by using fractional dosing we could rapidly and safely expand the number of effective doses of the Moderna and Pfizer vaccines.
Second, we embed fractional doses and other policies such as first doses first in a SIER model and we show that even if efficacy rates for fractional doses are considerably lower, dose-stretching policies are still likely to reduce infections and deaths (assuming we can expand vaccinations fast enough to take advantage of the greater supply, which is well within the vaccination frontier). For example, a half-dose strategy reduces infections and deaths under a variety of different epidemic scenarios as long as the efficacy rate is 70% or greater.
Third, we show that under plausible scenarios it is better to start vaccination with a less efficacious vaccine than to wait for a more efficacious vaccine. Thus, Great Britain and Canada’s policies of starting First Doses first with the AstraZeneca vaccine and then moving to second doses, perhaps with the Moderna or Pfizer vaccines is a good strategy.
It is possible that new variants will reduce the efficacy rate of all vaccines indeed that is almost inevitable but that doesn’t mean that fractional dosing isn’t optimal nor that we shouldn’t adopt these policies now. What it means is that we should be testing and then adapting our strategy in light of new events like a battlefield commander. We might, for example, use fractional dosing in the young or for the second shot and reserve full doses for the elderly.
One more point worth mentioning. Dose stretching policies everywhere are especially beneficial for less-developed countries, many of which are at the back of the vaccine queue. If dose-stretching cuts the time to be vaccinated in half, for example, then that may mean cutting the time to be vaccinated from two months to one month in a developed country but cutting it from two years to one year in a country that is currently at the back of the queue.
Read the whole thing.
The Becker-Friedman center also has a video discussion featuring my co-authors, Nobel prize winner Michael Kremer and the very excellent Witold Wiecek.
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?
Here’s Marty Makary, M.D., a professor of surgery and health policy at the Johns Hopkins University School of Medicine:
Finally, the FDA needs to stop playing games and authorize the Oxford-AstraZeneca vaccine. It’s safe, cheap ($2-$3 a dose), and is the easiest vaccine to distribute. It does not require freezing and is already approved and being administered in the United Kingdom.
Sadly, the FDA is months away from authorizing this vaccine because FDA career staff members insisted on another clinical trial to be completed and are punishing the company for inadvertently giving a half-dose of the vaccine to some people in the trial.
It’s like the FDA is holding out, pontificating existing excellent data and being vindictive against a company for making a mistake while thousands of Americans die each day.
Ironically, those in the Oxford-AstraZeneca trial who inadvertently received half the initial vaccine dose had lower infection rates. And this week Dr. Moncef Slaoui, the chief adviser to Operation Warp Speed, acknowledged that using half a dose might be a good broader strategy for the U.S. to double our supply as long our supply is severely constrained. That’s a good strategy that makes sense.
See also my post The AstraZeneca Factory in Baltimore. Thousands of people are dying every day. We have a vaccine factory ready to go. The FDA should lifts its ban on the AstraZeneca vaccine.
Emergent BioSolutions has a factory in Baltimore that operates under an innovative long-term private-partnership agreement with BARDA. Essentially BARDA subsidized the factory in return for an option to use it in an emergency–Operation Warp Speed exercised that option and in June-July AstraZeneca signed a licensing agreement with Emergent for large-scale manufacturing of its vaccine.
According to the Baltimore Sun the AZ vaccine is already being made at the facility. I hope they are making millions of doses. I want the AZ vaccine approved in the United States immediately but if we won’t take it (yet) they can still export it to Britain and the many other countries which will approve the vaccine.
More generally, there are three vaccines in the near term pipeline. AstraZeneca, Johnson and Johnson and Novavax. If there is anything that we can do to speed these vaccines to people it would be worth billions. All of these vaccine manufacturers should be making and storing millions of doses now.
It’s important to understand that a policy like First Doses First works best when capacity is increasing rapidly so approving these additional vaccines is part of an integrated plan.
Here’s the factory in Baltimore. It’s capable of producing tens to hundreds of millions of vaccine doses a year. Isn’t it beautiful?
Addendum: One more thing. Stop telling me that the problem is vaccine distribution not supply. Guess what? I am thinking ahead.
Federal health regulators have decided to allow the resumption of U.S. studies of a leading Covid-19 vaccine candidate from AstraZeneca PLC and the University of Oxford, according to a person familiar with the matter and materials reviewed by The Wall Street Journal.
Here is the WSJ article, no real explanation given by either the company or the FDA.
We are making all the same errors with monkeypox policy that we made with Covid but we are correcting the errors more rapidly. (It remains to be seen whether we are correcting rapidly enough.) I’ve already mentioned the rapid movement of some organizations to first doses first for the monkeypox vaccine. Another example is dose stretching. I argued on the basis of immunological evidence that A Half Dose of Moderna is More Effective Than a Full Dose of AstraZeneca and with Witold Wiecek, Michael Kremer, Chris Snyder and others wrote a paper simulating the effect of dose stretching for COVID in an SIER model. We even worked with a number of groups to accelerate clinical trials on dose stretching. Yet, the idea was slow to take off. On the other hand, the NIH has already announced a dose stretching trial for monkeypox.
Scientists at the National Institutes of Health are getting ready to explore a possible work-around. They are putting the finishing touches on the design of a clinical trial to assess two methods of stretching available doses of Jynneos, the only vaccine in the United States approved for vaccination against monkeypox.
They plan to test whether fractional dosing — using one-fifth of the regular amount of vaccine per person — would provide as much protection as the current regimen of two full doses of the vaccine given 28 days apart. They will also test whether using a single dose might be enough to protect against infection.
The first approach would allow roughly five times as many people to be vaccinated as the current licensed approach, and the latter would mean twice as many people could be vaccinated with existing vaccine supplies.
…The answers the study will generate, hopefully by late November or early December, could significantly aid efforts to bring this unprecedented monkeypox outbreak under control.
Another interesting aspect of the dose stretching protocol is that the vaccine will be applied to the skin, i.e. intradermally, which is known to often create a stronger immune response. Again, the idea isn’t new, I mentioned it in passing a couple of times on MR. But we just weren’t prepared to take these step for COVID. Nevertheless, COVID got these ideas into the public square and now that the pump has been primed we appear to be moving more rapidly on monkeypox.
Addendum: Jonathan Nankivell asked on the prediction market, Manifold Markets, ‘whether a 1/5 dose of the monkey pox vaccine would provide at least 50% the protection of the full dose?’ which is now running at a 67% chance. Well worth doing the clinical trial! Especially if we think that the supply of the vaccine will not expand soon.
My paper Testing fractional doses of COVID-19 Vaccines, co-authored with Kremer et al., has now been published at PNAS. I covered the paper in A Half Dose of Moderna is More Effective than A Full Dose of Astra Zeneca and other posts so I won’t belabor the basic ideas. One new point is that thanks to the indefatigable Michael Kremer and the brilliant Witold Wiecek, clinical trials on fractional dosing on a large scale have begun in Nigeria. Here are a few key points:
WHO SAGE Outreach: The authors have met and presented their work to the World Health Organization (WHO) Strategic Advisory Group of Experts on Immunization (SAGE), with follow-up meetings to present evidence coming from new studies.
DIL Workshop and Updates: In the fall of 2021, the Development Innovation Lab (DIL) at UChicago, led by Professor Kremer, hosted a workshop on fractional dosing, collecting updates from clinical researchers from multiple countries conducting fractional dosing trials for COVID-19 vaccines. The workshop also covered issues relating to trial design and included participants from Belgium, Brazil, Ghana, the Netherlands, Nigeria, Thailand, South Africa, UK and the US.
CEPI Outreach: Professor Kremer has also presented this research to The Coalition for Epidemic Preparedness Innovations (CEPI), which is now pursuing a platform trial of fractional dosing.
Country Trials – Nigeria: With the support of DIL and the research team and generous support and advice from WAM Foundation, the charitable arm of Weiss Asset Management and Open Philanthropy, a trial is being conducted in Nigeria by the Nigerian Institute of Medical Research, National Institute of Pharmaceutical Research and Development, National Agency for Food and Drug Administration and Control, and the National Primary Health Care Development Agency, in coordination with the Federal Ministry of Health.
A comprehensive list of all the trials on fractional dosing conducted to date is at the link. Fractional dosing may come too late for COVID-19 vaccines but perhaps next time a shortage of a vaccine looms we will be more quick to consider policies to stretch supplies.
As measured by page views here are the most popular MR posts of 2021. Coming in at number 10 was Tyler’s post:
Lots of good material there and well worth revisiting. Number 9 was by myself:
TDS infected many people but as the Biden administration quickly discovered the problems were much deeper than the president, leading to revisionism especially on the failures of the CDC and the FDA. Much more could be written here but this was a good start.
Number 8 was Tyler’s post:
which asked some good questions about a bad plan.
Sadly this post, written by me in January of 2021, had everything exactly right–we bottomed out at the end of June/early July as predicted. But then Delta hit and things went to hell. Sooner or later the virus makes fools of us all.
One of my earlier pieces (written in Feb. 21) on fractional dosing. See also my later post A Half Dose of Moderna is More Effective Than a Full Dose of AstraZeneca. We have been slow, slow, slow. I hope for new results in 2022.
Listener’s took umbrage, perhaps even on Tyler’s behalf, at Srinivasan but Tyler comes away from every conversation having learned something and that makes him happy.
Still true. Still jaw-dropping.
I let loose on the Biden administration’s silly attacks on vaccine patents. Also still true. Note also that as my view predicts, Pfizer has made many licensing deals on Paxalovid which has a much simpler and easier to duplicate production process (albeit raw materials are still a problem.)
A very good post, if I don’t say so myself, on this year’s Nobel prize recipients, Card, Angrist and Imbens.
Who else but Tyler?
To round out the top ten I’d point to Tyler’s post John O. Brennan on UFOs which still seems underrated in importance even if p is very low.
Erza Klein’s profile of me still makes me laugh, “He’s become a thorn in the side of public health experts…more than one groaned when I mentioned his name.” Yet, even though published in April many of these same experts are now openly criticizing the FDA and the CDC in unprecedented ways.
UFOs going mainstream or Tabarrok’s view of the FDA going mainstream. I’m not sure which of these scenarios was more unlikely ex ante. Strange world.
Let us know your favorite MR posts in the comments.
New paper published in Vaccines from Polish group showing that half doses of Pfizer generate strong immune responses.
In the context of the ongoing COVID-19 pandemic, using a half-dose schedule vaccination can help to return to normalcy in a cost-efficient manner, which is especially important for low and middle-income countries. We undertook a study to confirm that in adults up to 55 years old, the humoral response to the half-dose (15 µg, 35 participants between 18 and 55 years old) and to the recommended dose (30 µg, 155 participants) in the two-dose three-week interval schedule would be comparable. Antibody levels were measured by the Elecsys Anti-SARS-CoV-2 S assay (Roche Diagnostics, upper detection limit: 2570 BAU/mL) on the day of dose 2 of the vaccine and then 8–10 days later to assess peak response to dose 2. The difference in proportions between the participants who did and did not exceed the upper detection limit 8–10 days after dose 2 was not statistically significant (p = 0.152). We suggest that a half-dose schedule can help to achieve widespread vaccination coverage more quickly and cheaply.
See my previous piece A Half Dose of Moderna is More Effective Than a Full Dose of AstraZeneca.
Unless countries that have purchased vaccine doses and companies that have already brought vaccines into use agree to find ways to resolve the problem, manufacturers that trail the first wave of producers may not be able to prove that their vaccines work. Not only will that slow efforts to vaccinate the planet, it will block development of next-generation vaccines, and it will stymie efforts to answer key public health questions, like whether boosting with a different vaccine would generate better protection, or whether giving smaller — fractional — doses could protect more people more quickly…
The problem stems in part from the fact that at this point in the pandemic, it isn’t considered ethical to test new vaccines against placebos; instead they would have to be tested against one of the existing shots. But getting one’s hands on licensed or authorized vaccines for study purposes is nigh on impossible; all available doses have been snapped up by countries keen to vaccinate as many of their citizens as possible.
Contracts for those doses contain rigid stipulations about how the vaccines can be deployed. The doses often have to be used in the country that made the purchase; when the Biden administration wanted to share AstraZeneca doses with Canada and Mexico in March, it loaned the doses to get around the restrictions. Contracts also often stipulate that doses that have been purchased must be used for outbreak control, not for research purposes, Lurie said.
Here is the full story by Helen Branswell. Obviously there is a market-oriented solution here, if only we care enough to implement it…
1. Sarah Gilbert and Catherine Green, The Vaxxers: The Inside Story of the Oxford AstraZeneca Vaccine and the Race Against the Virus. Self-recommending (they were leaders on the team), most of all it is striking how much time they spend covering and complaining about problems in the science funding network. Let’s improve that. In any case I enjoyed the book.
2. Harald Jähner, Aftermath: Life in the Fallout of the Third Reich, 1945-55. A quite interesting book which considers how German women were disappointed in German men, how eastern German women dealt with Soviet soldier rape, how the Soviets resumed classical orchestral concerts within weeks (for their own pleasure), currency conversion, and more: “But Beate Uhse fell foul of the law for the first time, not because of violation of the moral code of corrupting the young, but for breach of price regluations.”
3. Jeevan Vasagar, Lion City: Singapore and the Invention of Modern Asia. Selective rather than comprehensive, but entertaining and balanced and insightful. Those interested in Singapore should read this book, and even Singapore experts will learn some new nuggets. The author was the FT correspondent in Singapore from 2015 to 2017.
4. Mathilde Fasting and Øystein Sørensen, The Norwegian Exception: Norway’s Liberal Democracy Since 1814. “This book started as an idea to explain Norwegian society to a broader public.” I am not sure they quite succeed, but still it is the best single Norway book I know. I hadn’t known for instance that Norway has two different official written languages. In general there should be more books trying to explain highly successful countries! This is a move in the right direction, and I am happy to see that the authors do not try to deny or run away from Norway’s first-rate performance.
5. James Hawes, The Shortest History of England. One can pick nits with books such as these, but I found this one useful. It stresses the role of the French in English history, and also the ongoing clash between the South and the North over who will rule whom.
There is also Robert Wuthnow’s Why Religion is Good for American Democracy (true), and Michael Taylor’s The Interest: How the British Establishment Resisted the Abolition of Slavery, which dashed my hopes when I learnt that Alexander McDonnell, the Belfast-born 19th century chess player who famously sparred with Louis de la Bourdonnais, also was a strongly pro-slavery and pro-imperialism economist in his time.
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.