Category: Law

The AstraZeneca trial is allowed to resume

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.

The window tax

The window tax in Great Britain (1696–1851) provides a remarkable case of tax-induced distortions in resource allocation. Tax liabilities on dwelling units depended on the number of windows in the unit. As a consequence, people boarded up windows and built houses with very few windows, to the detriment of both health and aesthetics. Using data from local tax records on individual houses, the analysis in the paper finds compelling evidence of such tax-avoidance and goes on to make a rough calculation of the excess burden associated with the tax.

Here is the full paper by Robert M. Schwab and Wallace E. Oates.

When in doubt, ask Alex Rampell

Alex is very very highly rated by those who know him, but still in the broader scheme of things significantly underrated as a Bay Area tech and finance thinker.  Here is Alex on SPACs:

If the best fundraise (IPO included) aggregates as many potential buyers as possible to raise money at the highest price with the least dilution and lowest fees, it’s hard to understand how a SPAC represents an improvement against those constraints. When a SPAC merges with a target (“de-SPACs”), it’s tantamount to an IPO. The SPAC (already publicly traded, with lots of cash on its balance sheet) and the target company agree on a pre-money valuation for the target; the money sitting in the SPAC becomes the “money raised” (IPO equivalent) with typically a PIPE (Private Investment in Public Equity, a further institutional fundraise / large block sale) done at the same time. As an example, a $500M SPAC might merge with a private company, ascribing a $4.5B valuation to the private company, meaning a $5B post-money valuation of the combined entity. How do we know *this* is the fair price? Should a company meet with one SPAC? Two SPACs? Three SPACs or four? Where is the price discovery?

And while the fee structure of SPACs will likely change, right now it is indisputably a more expensive option with less price discovery. Bankers are paid 5%+ for taking the SPAC public; SPAC investors typically get warrants with their investment; the SPAC sponsor typically gets 20% (of the pre-merger value of the SPAC) for finding a target, so 2% in the above example; a banker is normally hired and paid to handle the merger; a mini-roadshow happens to get approval from the SPAC shareholders AND to potentially secure more cash in the form of a PIPE, for which a banker is also paid.

Most of the post is on why IPOs are less inefficient than you might think, informative and interesting throughout.

My Conversation with Michael Kremer

Self-recommending, here is the transcript, audio, and video.  Here is part of the summary:

Michael joined Tyler to discuss the intellectual challenge of founding organizations, applying methods from behavioral economics to design better programs, how advanced market commitments could lower pharmaceutical costs for consumers while still incentivizing R&D, the ongoing cycle of experimentation every innovator understands, the political economy of public health initiatives, the importance of designing institutions to increase technological change, the production function of new technologies, incentivizing educational achievement, The Odyssey as a tale of comparative development, why he recently transitioned to University of Chicago, what researchers can learn from venture capitalists, his current work addressing COVID-19, and more.

Here is one excerpt:

COWEN: I’ve seen estimates — they’re actually from one of the groups you founded — that a deworming pill could cost as little as 50 cents a year per person in many parts of Africa. So why isn’t deworming done much more?

KREMER: You could say the glass is half empty, you can say it’s half full, or you can say it’s almost three-quarters full. I think it’s about three-quarters full. When I first got involved in deworming, it was testing a small NGO program. We found phenomenal effects of that. The original work found health gains and education gains. Now we’ve tracked people over 20 years, and we’re seeing people have a better standard of living or earning more.

Following the early results, we presented the results of the government of Kenya to the World Bank. Kenya scaled this up nationally, in part with assistance from the World Bank, primarily just in conveying some of that information.

Indian states started doing that, and then the national government of India took this on. They’re reaching — a little bit harder to know the exact numbers — but probably 150 million people a year. Many other countries are doing this as well, so it’s actually quite widely adopted.

COWEN: But there’s still a massive residual, right?

KREMER: That is for sure.

COWEN: What’s your best explanatory theory of why the residual isn’t smaller? It would seem to be a vote winner. African countries, fiscally, are in much better shape than they used to be. They’re more democratic. Public health looks much better. The response to COVID-19 has probably been better than many people expected, say, in Senegal, possibly in Kenya. So why not do deworming more?

KREMER: The people who have worms are pretty poor people. The richer people are less likely to have worms within a given society. Richer people are probably more politically influential.

There’s also something about worms — they gradually build up in your body, and one worm is not going to do that much damage. The problem is when you’ve got lots of worms in your body, and even there, it’s going to take time.

I’ve had malaria. I don’t think I’ve had worms. I hope I haven’t. When you have malaria, you feel terrible. You go from feeling fine to feeling terrible, and then you take the medicine. You feel great afterwards. With worms, it’s much more like a chronic thing, and when you expel the worms from your body, that’s sort of gross. I don’t think, even at the individual level, do you have quite the demand that would be commensurate with the scale of the problem. That’s a behavioral economics explanation.

I think there are political issues and then there are behavioral issues. I would actually say that a huge, huge issue . . . This sounds very boring, but this falls between the Ministry of Health and the Ministry of Education, and each one of them has different priorities. The Ministry of Health is going to be worried about delivering things through clinics. They’re worried about HIV and malaria, tuberculosis, as it should be.

The Ministry of Education — they’re worried about teacher strikes. It’s very easy for something to either fall between the cracks or be the victim of turf wars. It sounds too small to be, “How can that really get in the way?” But anybody who’s spent time working in governments understands those things can very easily get in the way. In some ways, it’s surprising how much progress has been made.

Here’s one way the political economy works in favor. You mentioned democracy — I think that’s a factor. I actually find — and I don’t want to be necessarily a big fan of politicians — but in some ways, politicians hear how much this costs, and they think they can affect that many people for that small amount of money, and they’re like, “Hey, I want to get on that. Maybe this is something I can claim as an achievement.” We saw that in Kenya. We saw that in India.

And:

COWEN: Let’s say the current Michael Kremer sets up another high school in Kenya. What is it that you would do that the current high schools in Kenya are not doing? What would you change? You’re in charge.

KREMER: Right. We’ve learned a lot in education research in recent years. One thing that we saw in Kenya, but was also seen in India and many other places, is that it’s very easy for kids to fall behind the curriculum. Curricula, in particular in developing countries, tend to be set at a fairly high level, similar to what you would see in developed countries.

However, kids are facing all sorts of disadvantages, and there are all sorts of problems in the way the system works. There’s often high teacher absence. Kids are sick. Kids don’t have the preparation at home, often. So kids can fall behind the curriculum.

Whereas we’ve had the slogan in the US, “No Child Left Behind,” in developing countries, education system is focused on kids at the top of the distribution. What’s been found is, if you can set up — and there are a whole variety of different ways to do this — either remedial education systems or some technology-aided systems that are adaptive, that go to where the kid is . . . I’ve seen huge gains from this in India, and we’re starting to see adoption of this in Africa as well, and that can have a very big impact at quite low cost.

Intelligent throughout.

Should government improve the quality of its software?

From a GitHub repository:

This GitHub repository is a back up of my FAERSFix scripts.

The FDA Adverse Effect Reporting System is a horrifically dysfunctional quagmire of shockingly bad data. The data is not just bad for severe epistemological reasons, it is also poorly organized and riddled with flagrant absurd errors.

These scripts smooth over the very messy process of acquiring and basic debugging of the data. At the end of the process a user can arrive at a local repository of the FAERS data that is sane enough to begin to think about some kind of sensible analysis. To understand the disastrous state of the original source data, see the source code of the scripts which is designed to be a readable self-documenting manual demonstrating how to correct this mess.

Since the FDA’s gremlins never rest, these scripts will become obsolete. If you would like to contribute updates or fixes, feel free to send me a patch or a pull request. Good luck!

I thank Chris E. for the pointer.

The AstroZeneca saga, according to one source

This seems unconfirmed, and do note some sources in the story do not believe this account, but here goes:

AstraZeneca, whose Phase 3 coronavirus vaccine clinical trial has been on hold for more than a month, did not get critical safety data to the US Food and Drug Administration until last week, according to a source familiar with the trial.

The FDA is considering whether to allow AstraZeneca to restart its trial after a participant became ill. At issue is whether the illness was a fluke, or if it may have been related to the vaccine.

The source said the root of the delay is that the participant was in the United Kingdom, and the European Medicines Agency and the FDA store data differently.

“They had to convert data from one format to another format. It’s like taking stuff off a PC and putting it onto an Apple. They had to spend a lot of hours to get what they wanted,” the source said.

On Friday, a federal official hinted there might be some word this week on the trial’s future.

Or maybe they just fooled CNN with it?

Otherwise, good thing we are kept safe from such dangerous data formats!  Would it really not be better to move to reciprocal recognition procedures?  Not to mention a unified data format, or perhaps some FDA methods to read data produced for the EU?

For the pointer I thank Jackson Stone.

And yet the American trial remains suspended

Those nasty, reckless Brits:

The NHS is preparing to introduce a coronavirus vaccine soon after Christmas. Trials have shown it will cut infections and save lives, Jonathan Van-Tam, the deputy chief medical officer, has privately revealed.

He told MPs last week that stage three trials of the vaccine created at Oxford University and being manufactured by AstraZeneca mean a mass rollout is on the horizon as early as December. Thousands of NHS staff are to undergo training to administer a vaccine before the end of the year.

The government changed the law this weekend to expand the number of health professionals able to inoculate the public. The regulations will enable pharmacists, dentists, midwives and paramedics to administer jabs.

C’mon U.S. public health authorities, let’s get on this one and demand a resumption of the suspended AstraZeneca trial.  You are advocates of science, right?  You don’t actually want to make Donald Trump correct, do you?  (Maybe that one will work.)

You don’t have to make it the vaccine, as the Brits seem to be doing, you just have to resume the trial, as the even more reckless Japanese did weeks ago.  How about it?

Here is the article from Times of London (gated, but a cheap and worthwhile subscription for foreigners), via Linda Yueh.

Solve for the China equilibrium

Chinese government officials are warning their American counterparts they may detain U.S. nationals in China in response to the Justice Department’s prosecution of Chinese military-affiliated scholars, according to people familiar with the matter.

The Chinese officials have issued the warnings to U.S. government representatives repeatedly and through multiple channels, the people said, including through the U.S. Embassy in Beijing.

The Chinese message, the people said, has been blunt: The U.S. should drop prosecutions of the Chinese scholars in American courts, or Americans in China might find themselves in violation of Chinese law.

Here is more from the WSJ.  Three to four years ago I used to explain to friends and family that I needed to visit China as much as possible very quickly, because soon enough my opportunities would be over.  And it seems that now — even without the Covid factor — we have reached that point.

Why I reject the Great Barrington Declaration

Here is my 2x normal length Bloomberg column on that topic, as had been requested by Daniel Klein.  The argument has numerous twists and turns, do read the whole thing but here is one bit (I will indent only their words):

“Here are the key words of the Great Barrington Declaration on herd immunity:

The most compassionate approach that balances the risks and benefits of reaching herd immunity, is to allow those who are at minimal risk of death to live their lives normally to build up immunity to the virus through natural infection, while better protecting those who are at highest risk. We call this Focused Protection.

What exactly does the word “allow” mean in this context? Again the passivity is evident, as if humans should just line up in the proper order of virus exposure and submit to nature’s will. How about instead we channel our inner Ayn Rand and stress the role of human agency? Something like: “Herd immunity will come from a combination of exposure to the virus through natural infection and the widespread use of vaccines. Here are some ways to maximize the role of vaccines in that process.”

And the close:

“In most parts of the Western world, normal openings for restaurants, sporting events and workplaces are likely to lead to spiraling caseloads and overloaded hospitals, as is already a risk in some of the harder-hit parts of Europe. Reopenings, to the extent they work, rely on a government that so scares people that attendance remains low even with reopening.

In that sense, as things stand, there is no “normal” to be found. An attempt to pursue it would most likely lead to panic over the numbers of cases and hospitalizations, and would almost certainly make a second lockdown more likely. There is no ideal of liberty at the end of the tunnel here.

Don’t get me wrong: The Great Barrington strategy is a tempting one. Coming out of a libertarian think tank, it tries to procure maximum liberty for commerce and daily life. It is a seductive idea. Yet consistency of message is not an unalloyed good, even when the subject is liberty…

My worldview is both more hopeful and more tragic. There is no normal here, but we can do better — with vigorous actions to combat Covid-19, including government actions. The conception of human nature evident in the Great Barrington Declaration is so passive, it raises the question of whether it even qualifies as a defense of natural liberty.”

MR Tyler again: You will note I do not make the emotional, question-begging argument that herd immunity strategies will kill millions (though I do think more people die under that scenario).  If you argue, as many herd immunity critics do, that the elderly cannot be isolated, it seems you also should not be entirely confident that the currently non-infected can be isolated.  The brutal truth is simply that a Great Barrington strategy put into practice would lead to rapidly spiraling cases and a rather quick and oppressive second lockdown, worse than what the status quo or some improved version of it is likely to bring.  Total deaths are likely higher, along with more social trauma, due to the more extreme whipsaw effects, but no not by millions.

Let’s accelerate those biomedicals, people!

From the comments, on AstraZeneca vaccine trial resumption

America is really, really messed up.

The only place with such intensely wasteful discussions about a disease is the U.S. And it is getting increasingly easy to ignore the U.S. as the world continues to respond to this pandemic.

And it is not just the British based trial. This is from Reuters on Sept. 14 – “Clinical trials for the coronavirus vaccine being developed by AstraZeneca PLC and Oxford University resumed in Brazil on Monday after the country’s health regulator got confirmation over the weekend that its British equivalent MHRA had approved the restart, a company representative said.

The Federal University of Sao Paulo, which is running the trials, said in a statement that 4,600 of the planned 5,000 volunteers have been vaccinated in Brazil without any of them reporting any serious health issues.”

This from the Times of India on Sept 20th -“The phase-III human clinical trial of the COVID-19 vaccine developed by Oxford University and being manufactured by the Serum Institute of India (SII) will begin at the Sassoon General Hospital in Pune next week. Dean of the state-run Sassoon General Hospital Dr Muralidhar Tambe told this to on Saturday.

“The phase-III trial of ‘Covishield’ vaccine will begin at Sassoon hospital from next week. It is likely to start on Monday. Some volunteers have already come forward for the trial. Around 150 to 200 volunteers will be administered the vaccine candidate dose,” he said.

Regulators in Japan and South Africa also have no problem with the trial continuing.

That is from Easy-Peasy.  And I did google to ensure that those claims about foreign trial resumption are correct, for instance Japan resumed no later than October 2.  This is one reason — not the only! — why I am puzzled when Derek Lowe claims on Twitter that American perhaps cannot go any faster with its vaccine.  If you think Japan and the Brits are irresponsible, by all means let us know.  Otherwise…it is time to speak up in favor of maximizing expected value.

Model this

Nancy Pelosi warned that a Covid-19 vaccine should not be authorised for use in the US based on data from British trials, amid fears that the Trump administration is planning to rush out an inoculation before election day.

The Democratic speaker of the House of Representatives on Friday cast doubt on the British system for testing and approving medicines, further politicising the race to develop a vaccine for Covid-19.

“We need to be very careful about what happens in the UK. We have very stringent rules in terms of the Food and Drug Administration here, about the number of clinical trials, the timing, the number of people and all the rest,” Ms Pelosi told reporters in Washington.

Here is the full FT story, and here is a nice NYT piece, by Zeke Emanuel and others, on the superiority of the British clinical trials system, especially with respect to Covid-19.

Monoclonal antibodies are doing very well

In the study, 112 patients received 2.8 grams of each of the antibodies, and 156 received placebo. The difference in viral load was statistically significant at day 11, unlike some doses of Lilly’s single-antibody cocktail. There was also a statistically significant reduction in viral levels three days and seven days after infection.

The treatment also improved symptoms, according to a scored questionnaire, and resulted in fewer hospital and emergency room visits. Visits to the hospital or ER were made by 5.8% of patients in the placebo group, but just 0.9% of those who received the antibody combination. That difference, however, was just barely statistically significant.

Lilly said that it has already begun talking to regulators around the world about its single antibody treatment, and has filed with the Food and Drug Administration for an emergency use authorization…

Lilly said it anticipates it could have as many as 1 million doses of its one-antibody treatment, LY-CoV555, available in the fourth quarter of 2020, with 100,000 available this month. But for the combination therapy, just 50,000 doses will be available in the fourth quarter of 2020.

Both antibody regimens have been well-tolerated, with no serious side effects, the company said.

Here is the full story from StatNews.  Big news, but not a surprise to everyone.

My Conversation with Audrey Tang

For me one of the most fun episodes, here is the audio, video, and transcript.  And here is the longer than ever before summary, befitting the chat itself:

Audrey Tang began reading classical works like the Shūjīng and Tao Te Ching at the age of 5 and learned the programming language Perl at the age of 12. Now, the autodidact and self-described “conservative anarchist” is a software engineer and the first non-binary digital minister of Taiwan. Their work focuses on how social and digital technologies can foster empathy, democracy, and human progress.

Audrey joined Tyler to discuss how Taiwan approached regulating Chinese tech companies, the inherent extraterritoriality of data norms, how Finnegans Wake has influenced their approach to technology, the benefits of radical transparency in communication, why they appreciate the laziness of Perl, using “humor over rumor” to combat online disinformation, why Taiwan views democracy as a set of social technologies, how their politics have been influenced by Taiwan’s indigenous communities and their oral culture, what Chinese literature teaches about change, how they view Confucianism as a Daoist, how they would improve Taiwanese education, why they view mistakes in the American experiment as inevitable — but not insurmountable, the role of civic tech in Taiwan’s pandemic response, the most important remnants of Japanese influence remaining in Taiwan, why they love Magic: The Gathering, the transculturalism that makes Taiwan particularly open and accepting of LGBT lifestyles, growing up with parents who were journalists, how being transgender makes them more empathetic, the ways American values still underpin the internet, what he learned from previous Occupy movements, why translation, rotation, and scaling are important skills for becoming a better thinker, and more.

This bit could have come from GPT-3:

COWEN: How useful a way is it of conceptualizing your politics to think of it as a mix of some Taiwanese Aboriginal traditions mixed in with Daoism, experience in programming, and then your own theory of humor and fun? And if you put all of that together, the result is Audrey Tang’s politics. Correct or not?

TANG: Well as of now, of course. But of course, I’m also growing, like a distributed ledger.

And this:

COWEN: You’re working, of course, in Taiwanese government. What’s the biggest thing wrong with economists?

TANG: You mean the magazine?

COWEN: No, no, the people, economists as thinkers. What’s their biggest defect or flaw?

TANG: I don’t know. I haven’t met an economist that I didn’t like, so I don’t think there’s any particular personality flaws there.

Finally:

COWEN: Now, my country, the United States, has made many, many mistakes at an almost metaphysical level. What is it in the United States that those mistakes have come from? What’s our deeper failing behind all those mistakes?

TANG: I don’t know. Isn’t America this grand experiment to keep making mistakes and correcting them in the open and share it with the world? That’s the American experiment.

COWEN: Have we started correcting them yet?

TANG: I’m sure that you have.

Definitely recommended.

Why are North and South India so different on gender?

From Alice Evans:

Region is a strong predictor of female survival, literacy, autonomy, employment, and independent mobility. A woman with the exact same household wealth/ caste/ religion will likely have more autonomy if she lives in the South.

It does not seem to be a function of wealth, nor was colonialism a major factor.  And cousin marriage, which is more prevalent in the south?  Alice notes:

Southern women may have gained autonomy despite cousin marriage, not because of it.

Islam, however, is one factor:

In sum, gender segregation became more widespread under Islamic rule. Men continue [to] dominate public life, while women are more rooted in their families, seldom gathering to resist structural inequalities.

But perhaps most significantly:

Female labour force participation is higher in states with traditions of labour-intensive cultivation…

Wheat has been grown for centuries on the fertile, alluvial Indo-Gangetic plain. Cultivation is not terribly labour-intensive, though cereals must still be processed, shelled and ground. This lowers demand for female labour in the field, and heightens its importance at home.

Rice-cultivation is much more labour intensive. It requires the construction of tanks and irrigation channels, planting, transplanting, and harvesting. Women are needed in the fields. Rice is the staple crop in the South.

And this:

Pastoralism may have also influenced India’s caste-system. Brahmins dominate business, public service, politics, the judiciary, and universities. Upper caste purity and prestige has been preserved through female seclusion, prohibiting polluting sexual access. These patriarchal norms may be rooted in ancient livelihoods. Brahmins share genetic data with ancient Iranians and steppe pastoralists. Brahmins also comprise a larger share of the population in North India and only 3% in Tamil Nadu.

Over the centuries, male superiority may have become entrenched.

Finally:

Northern parents increasingly support their daughters’ education, but this is primarily to improve their marriage prospects, not work outside the home.

There is much, much more at the link, including some excellent maps, visuals, and photos.

Is it wrong if I ask for the same?

In an interview Friday afternoon, Regeneron’s chief executive, Dr. Leonard S. Schleifer, said Mr. Trump’s medical staff reached out to the company for permission to use the drug, and that it was cleared with the Food and Drug Administration.

“All we can say is that they asked to be able to use it, and we were happy to oblige,” he said. He said that so-called compassionate use cases — when patients are granted access to an experimental treatment outside of a clinical trial — are decided on a case-by-case basis and he is not the first patient to granted permission to use the treatment this way. “When it’s the president of the United States, of course, that gets — obviously — gets our attention.”

In my non-specialist but not entirely uninformed opinion, this is basically an effective treatment, and barring major unobserved genetic risk factors Trump will recover.  The risk of side effects is not significant.  But of course neither the FDA nor Regneron will let me do the same.  Or you.

There is such cacophony when Trump pushes the FDA to speed vaccine approval — mere pressure rather than an action.  Yet when he actually gets a promising treatment through the process “prematurely” — only for himself — not a single person is yelping.  Not even his worst enemies and most vicious opponents.  Nor do I see anyone arguing that the President is being allowed to take excess risk, and that the judgments of the regulators should be enforced consistently and for the good of the office of the presidency.

Nope.  Model that!  (Hint: start with the idea of status.)

In the meantime, I think the common intuition about the Trump monoclonal antibodies case is essentially correct, and it ought to be applied most broadly.  And not just for presidents.

Here is the full NYT story.