Tyrone on clinical trials and how to keep them up and running
Tyrone — my evil twin brother — received so much hate and love mail from his recent pronouncements about QAnon that he felt emboldened to offer additional opinions. As you might expect, he prefers to spew his hateful bile on matters of life and death. In particular, he has been following the debates about Covid and whether new treatments should be accelerated in their availability. Anyway, I told him I was willing to pass along another of his letters, as a kind of experiment (not quite a clinical trial) whether Tyler or Tyrone is a more beloved writer on MR. I am sure you readers — and especially commentators — stand ready to defend my honor!
So here is his (as usual) fallacy-ridden missive:
Tyler, I don’t see why you let the defenders of FDA stalling get away with their dawdling. They all end up with the same argument — if we let wonderful, salt of the earth Americans take beneficial medicines, treatments, and vaccines, we will not be able to set up informative clinical trials. Why partake in the trial when you can just get the stuff through normal means?
That is so lame! First, they could simply pay people to partake in those trials. Isn’t that in essence what the NBA did with its Covid testing in the bubble? If the value of those clinical trials truly is so high, it should be possible to internalize enough of those benefits to encourage participation. If institutional barriers stand in the way there, let’s obsess over fixing those.
Why should we force so many Americans to be sacrificial lambs, just to subsidize the trial costs? Let those costs be taken out of grant overhead! (And admin. salaries, if need be.)
If the current medical establishment is not as able as the NBA, well OK, can’t they just admit it and plead patheticness? We can send them to take care of Major League Baseball, and put Adam Silver and Lebron James in charge of our health care.
Second, there is another way to keep the trial up and running. Approve use of the treatment, but allow the suppliers to charge very high prices! Better yet, use the law to make them charge high prices and if need be forbid insurance coverage.
“What will it be sucker? Fifty percent chance of the placebo, or 100k for those monoclonal antibodies?”
I assure you Tyler that will restore a separating equilibrium. Furthermore, in the meantime only the most meritocratic of wealthy men will get the treatment outside of the trial, all for the better. If need be, you can pull away the price floor when the clinical trial is complete, in the meantime you have satisfied the Pareto principle.
And what about the Hippocratic Oath ? “Do no harm”? Is that not invoked so selectively by the public health commentators? Surely you realize they court public opinion and high status by taking sins of commission far more seriously than the far less visible sins of omission?
Is it not harm to deny patients ready accessibility to a treatment with positive expected value?
Is it really such a great rejoinder to insist “We can’t let those patients improve their lot by raising pecuniary costs for the medical professionals running their trials! That is true Hippocratic harm and must be avoided at all costs, because in fact we medical people would be too feckless to overcome that problem…”
Sigh. At that point I had to stop reading and transcribing. I am sorry readers, I didn’t know that Tyrone in his spare time was studying economics and indeed some logic as well. Maybe he has even been reading MR. That makes him less interesting, less funny, and maybe a bit too much like Tyler. That is not why you come to read Tyrone, and indeed you might as well be reading Tyler.
What can I do to make Tyrone better and more eccentric again? Perhaps try to get him premature access to some of those special treatments? Stay tuned….
New Emergent Ventures anti-Covid prize winners
The first new prize is to Anup Malani of the University of Chicago, with his team, for their serological research in India and Mumbia. They showed rates of 57 percent seroprevalance in the Mumbai slums, a critical piece of information for future India policymaking. Here is the research.
Professor Malani is now working in conjunction with Development Data Lab to extend the results by studying other parts of India.
The second new prize goes to 1Day Sooner, a 2020-initiated non-profit which has promoted the idea of Human Challenge Trials for vaccines and other biomedical treatments. Alex here covers the pending HCTs in Britain, as well as providing links to previous MR coverage of the topic.
I am delighted to have them both as Emergent Ventures prize winners.
Here are the first, second, and third cohorts of winners of Emergent Ventures prizes against Covid-19.
Sunday assorted links
1. My May predictions about the NBA bubble.
3. A second wave of Covid infections for London health care workers.
4. Floodgates work in Venice in first major test (NYT).
5. Borgen it ain’t: “The 15-year-old he slept with was member of the junior wing of the Social Democrats.”
6. Resource on aerosol transmission information.
7. Devaki Jain trauma harassment story. Now he is all the more the least deserving economics Nobel laureate.
UK hospitals are already using monoclonal antibodies
Here is the story, note the treatment is making a very good impression:
Prof Peter Horby, who is part of Oxford University’s national Recovery trial, which aims to identify potential treatments for Covid-19, said “about three hospitals in the north” began using the drug last weekend. He said the drug was due to be rolled out to another 30 to 40 UK hospitals next week.
He told BBC Radio 4’s Today programme that the drug, REGN-COV2, was “very promising” and “very potent”.
“The class of drugs, these artificial antibodies, have been around for quite a while now, and they’ve been extensively used in inflammatory conditions and cancers, and they’re pretty safe and well understood, and so the technology is something that I think we have confidence in,” Horby said.
“This particular drug has probably been given to, I would think now, four or five hundred patients, mild or severe patients in different trials, and so far there’s been no worrying safety signals.
“In the laboratory, in cell cultures, it has a very strong effect against the virus, and there have been studies in artificial animals where it also shows benefits. So probably of the drugs that are available, it’s one of the most promising.”
Horby said a single dose of the treatment provided prolonged protection for a month to six weeks, making it “quite attractive for the older population”.
I hope Donald Trump “twists” the arms of the scientists at the FDA into speedy Emergency Use Authorization, and “politicizes” them into doing the right thing.
Twist, Donald! Yes, they are accountable too. Twist harder! That’s why we gave you the monoclonal antibodies.
And please don’t tell me in response that we can expect ordinary Americans to apply for the compassionate use exception, or sign up for clinical trials.
What I’ve been reading
1. Matthew Hongoltz-Hetling, A Libertarian Walks Into a Bear: The Utopian Plot to Liberate an American Town (And Some Bears). A fun look at the Free Town project as applied to Grafton, New Hampshire: “During a television interview, a Grafton resident accused the Free Towners of “trying to cram freedom down our throats.””
2. Cass R. Sunstein and Adrian Vermeulen, Law & Leviathan: Redeeming the Administrative State. Self-recommending from the pairing alone, there is a great deal of interesting content in the 145 pp. of text. It is furthermore an interesting feature of this book that it was written at all on the chosen topic. Perhaps the administrative state is under more fire than I realize. And might you consider this book a centrist version of…maybe call it “state capacity not quite libertarianism”?
3. Michael D. Gordin, The Pseudo-Science Wars: Immanuel Velikovsky and the Birth of the Modern Fringe. A somewhat forgotten but still fascinating episode in the history of science, extra-interesting for those interested in Venus. I had not known that Velikovsky pushed a weird version of a eugenicist theory stating that Israel was too hot for its own long-term good, and that its inhabitants needed to find ways of cooling it down.
4. History, Metaphor, Fables: A Hans Blumenberg Reader, edited by Bajohr, Fuchs, and Kroll. I love Blumenberg, but the selection here didn’t quite sell me. Better to start with his The Legitimacy of the Modern Age, noting that book is a tough climb for just about anyone and it requires your full attention for some number of weeks. Might Blumenberg be the best 20th thinker who isn’t discussed much in the Anglo-American world? And yes it is Progress Studies too.
5. Laura Tunbridge, Beethoven: A Life in Nine Pieces. Smart books on Beethoven are like potato chips, plus you can listen to his music while reading (heard Op.33 Bagatelles lately?). In addition to some of the classics, this book covers some lesser known pieces such as the Septet, An die Ferne Geliebte, and the Choral Fantasy, and how they fit into Beethoven’s broader life and career. Intelligent throughout.
6. Sean Scully, The Shape of Ideas, edited and written by Timothy Rub and Amanda Sroka. Is Scully Ireland’s greatest living artist? He has been remarkably consistent over more than five decades of creation. This is likely the best Scully picture book available, and the text is useful too. Since it is abstract color and texture painting, he is harder than most to cancel — will we see the visual arts shift in that direction?
Jonathan E. Hillman, The Emperor’s New Road: China and the Project of the Century, is a good introduction to its chosen topic.
Robert Litan, Resolved: Debate Can Revolutionize Education and Help Save Our Democracy: “…incorporate debate or evidence-based argumentation in school as early as the late elementary grades, clearly in high school, and even in college.”
I am closer to the economics than the politics of Casey B. Mulligan, You’re Hired! Untold Successes and Failures of a Populist President, but nonetheless it is an interesting and contrarian book, again here is the excellent John Cochrane review.
There is also Harriet Pattison, Our Days are Like Full Years: A Memoir with Letters from Louis Kahn, a lovely romance with nice photos, sketches, and images as well, very nice integration of text and visuals.
Is the treatment positive expected value, or negative expected value?
Well, which one is it?
If you consider the treatments of remdesivir or monoclonal antibodies for President Trump, their application is either positive expected value or negative expected value.
If they are positive expected value, you should be for using them! (I don’t mean that as a political statement, sub in another patient’s name if you need to.)
If they are negative expected value, you should oppose the current widespread use of remdesivir in hospitals (not necessarily in every case, of course), and you should probably oppose the Advance Market Commitment already in place for Regeneron’s monoclonal antibody treatment, not to mention its successful advance through various trials.
I don’t see anyone taking those stances.
Instead, I see commentators — including highly esteemed public health experts — claiming there is not yet enough data, “expressing reservations,” referring to other public health catastrophes, referring to more general irresponsible habits of the patient under consideration, and serving up various other rhetorical devices to indicate a negative attitude toward the treatment without actually saying “I think this treatment is negative expected value.”
That is a very bad thought and writing habit!
Made worse by Twitter, I might add. You are trying to create negative affect and mood affiliation without making the corresponding epistemic and predictive commitment.
Please just say you think it is negative expected value, and then apply that view consistently across the board. Stand your ground and defend it.
Or if you think it is positive expected value, praise its use, and then of course it is fine to add qualifiers and reservations.
If you genuinely have no opinion (ha), it is fine to say that too, but then you can drop the negative rhetoric and maybe don’t tweet about it at all.
To be sure, there are various heterogeneities and I am not applying the appropriate qualifiers in each sentence above, for reasons of expositional convenience. For instance, is Trump different from other patients? Are the treatments being applied at the right time? Who exactly has the private information here? And so on. Incorporating those factors should not change the basic analysis above, though for the most part they should push you toward a more positive attitude toward the treatments.
Saturday assorted links
The problem with rapid Covid testing
Mayank Gupta emails me:
The absolute number of false positives would rise dramatically under slightly inaccurate, broad surveillance testing. At least initially, the number of people going to the doctor to ask what to do would also rise. One can imagine if doctors truly flubbed and didn’t know how to advise patients accurately, a lot of individual patients would lose trust in the medical system (testing, doctors, or both). The consequence of this would be more resistance to health public policy measures in the future.
I see this as quite similar to what happened on three mile island. There was a clear utilitarian benefit to taking on some small amount of nuclear accident risk. The public was never taught how or why to internalize and cope with this risk. When the risk manifested, individuals saw the risk but not the public benefit and turned against nuclear. This change of public opinion was reflected in public policy after.
I’m sure there’s some mismatches in this analogy, but I’m using it to point out that in general I find thinking on the margin without thinking about the public’s ability to think on the margin can result in setbacks on the margin.
In an age where science is both more capable of solving social problems and more complex to understand, but the public has too much complex information to sort through, the central problem of governance seems to be how to solve public choice, without creating a monopoly on information.
To be clear, I do favor rapid testing, but it is worth giving this problem further thought.
The social function of Harvard and other elite universities
Here is a new study by Valerie Michelman, Joseph Price, and Seth D. Zimmerman:
This paper studies social success at elite universities: who achieves it, how much it matters for students’ careers, and whether policies that increase interaction between rich and poor students can integrate the social groups that define it. Our setting is Harvard University in the 1920s and 1930s, where students compete for membership in exclusive social organizations known as final clubs. We combine within-family and room-randomization research designs with new archival and Census records documenting students’ college lives and career outcomes. We find that students from prestigious private high schools perform better socially but worse academically than others. This is important because academic success does not predict earnings, but social success does: members of selective final clubs earn 32% more than other students, and are more likely to work in finance and to join country clubs as adults, both characteristic of the era’s elite. The social success premium persists after conditioning on high school, legacy status, and even family. Leveraging a scaled residential integration policy, we show that random assignment to high-status peers raises rates of final club membership, but that overall effects are driven entirely by large gains for private school students. Residential assignment matters for long-run outcomes: more than 25 years later, a 50-percentile shift in residential peer group status raises the rate at which private school students work in finance by 37.1% and their membership in adult social clubs by 23.0%. We conclude that the social success premium in the elite labor market is large, and that its distribution depends on social interactions, but that the inequitable distribution of access to high-status social groups resists even vigorous attempts to promote cross-group cohesion.
You can think of this as another attempt to explain the relatively high returns to education, without postulating that students learn so much, and without emphasizing signaling so much. Going to Harvard is in fact winning access to a very valuable set of networks (which in turn is signaling as well, to be clear).
For the pointer I thank Tyler Ransom.
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.
The roots of fascism in Italy, namely communism
In this paper, we argue that there was a strong link between the surge of support for the Socialist Party after World War I (WWI) and the subsequent emergence of Fascism in Italy. We first develop a source of variation in Socialist support across Italian municipalities in the 1919 election based on war casualties from the area. We show that these casualties are unrelated to a battery of political, economic and social variables before the war and had a major impact on Socialist support (partly because the Socialists were the main anti-war political movement). Our main result is that this boost to Socialist support (that is “exogenous” to the prior political leaning of the municipality) led to greater local Fascist activity as measured by local party branches and Fascist political violence (squadrismo), and to significantly larger vote share of the Fascist Party in the 1924 election. We document that the increase in the vote share of the Fascist Party was not at the expense of the Socialist Party and instead came from right-wing parties, thus supporting our interpretation that center-right and right-wing voters coalesced around the Fascist Party because of the “red scare”.
That is from a new paper by Daron Acemoglu, Giuseppe De Feo, Giacomo De Luca, and Gianluca Russo.
Friday assorted links
1. Were the experts too slow to embrace travel restrictions? (NYT) And the Covid culture that is German (short video).
2. Does personality drive moral judgement?: Polite deontologists and curious consequentialists.
3. My rewrite of this thread: doctors hate highly beneficial but somewhat inaccurate testing methods that lower their status and good feelings about themselves.
4. Further results on “dry tinder” in the Nordics: “My results show that a large share of the excess mortality in Sweden in April 2020 may be partially explained by a vulnerable, elderly population due to very mild flu seasons in 18/19 and 19/20 as well as very few deaths during the 2019 summer compared to earlier years and compared to other Nordic countries.”
5. John Cochrane on political diversity in the AEA.
You can all have your discussion here
Comments are open. But if you as a reader click on the comments link, the fault is yours not mine.
The elasticity of science
By Kyle Myers:
This paper identifies the degree to which scientists are willing to change the direction of their work in exchange for resources. Data from the National Institutes of Health are used to estimate how scientists respond to targeted funding opportunities. Inducing a scientist to change their direction by a small amount—to work on marginally different topics—requires a substantial amount of funding in expectation. The switching costs of science are large. The productivity of grants is also estimated, and it appears the additional costs of targeted research may be more than offset by more productive scientists pursuing these grants.
Here is the full article in American Economic Journal: Applied Economics.
New issue of Econ Journal Watch
https://econjwatch.org/issues/volume-17-issue-2-september-2020
In this issue:
Five cities, five stories? Robert Kaestner explores the heterogeneity of results across Baltimore, Boston, Chicago, Los Angeles, and New York in the work of Raj Chetty, Nathaniel Hendren, and Lawrence Katz, arguing that it is misleading to suggest that moving before the age of 13 to lower-poverty neighborhoods promises better outcomes. Chetty, Hendren, and Katz respond.
The AEA: Republicans need not apply: Mitchell Langbert investigates the American Economic Association, using voter-registration data and political-contribution data to show that the AEA officers, editors, authors, and other players are quite thoroughgoingly Democratic.
The AER: How much space is given to articles on gender, race and ethnicity, and inequality?: Jeremy Horpedahl and Arnold Kling track the trends 1991–2020 for the American Economic Review and Papers & Proceedings.
Lockdowns and covid hospitalizations: John Spry criticizes a JAMA research letter by Soumya Sen, Pinar Karaca-Mandic, and Archelle Georgiou about the effectiveness of stay-at-home orders, for eliding available placebo comparisons. Sen, Karaca-Mandic, and Georgiou reply.
Reading, writing, and Adam Smith: Scott Drylie uses Smith’s final words on school financing to review interpretations of Smith on schooling.
Carl Menger: The Errors of Historicism in German Economics: The first English translation of Menger’s 1884 reply to Gustav Schmoller is provided by Karen Horn and Stefan Kolev, whose Foreword analyzes the not-so-amicable Methodenstreit.
Data alteration: Ron Michener rejoins to Farley Grubb, explaining why he thinks that Grubb had no grounds for altering John McCusker’s data series and thereby generating outliers on which his results depend. (Professor Grubb received Professor Michener’s comment too late to allow for concurrent reply but will reply in the next issue of this journal.)
Frictionless note: With the approval and gratitude of Jeffrey Bergstrand, Nico Stoeckmann corrects the constant in the equation for a special, frictionless case of Bergstrand’s gravity equation for international trade.
Liberalism in Brazil: Lucas Berlanza provides a historical and modern guide to the fortunes of liberal ideas and trends in Brazil, extending the Classical Liberalism in Econ, by Country series to 20 articles.
Readworthy 2050: Nine correspondents respond to the question: What 21st-Century Works Will Merit a Close Reading in 2050?
EJW Audio:
Karen Horn and Stefan Kolev on Menger vs. Schmoller: The translators discuss Menger’s 1884 The Errors of Historicism in German Economics and the broader Methodenstreit.
Arnold Kling on Why Edward Leamer Deserves a Nobel Prize
Evan Osborne on Joan Robinson’s Little-Repented Maoism