Category: Science

Tyrone on clinical trials and how to keep them up and running

by  Tyler Cowen in

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….

Is the treatment positive expected value, or negative expected value?

by  Tyler Cowen in

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.

The problem with rapid Covid testing

by  Tyler Cowen in

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 elasticity of science

by  Tyler Cowen in

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.

Ho hum

by  Tyler Cowen in

Compact Nuclear Fusion Reactor Is ‘Very Likely to Work,’ Studies Suggest (NYT)

What else have we got this year?  Visiting alien drones, life on Venus and Mars, super-acceleration of vaccine production techniques, Tesla valued at mega-levels, and plummeting prices for solar panels.

Remember what I wrote in the final section of The Great Stagnation?  I predicted you’ll all be super-pissed off when it ends.

Decentralized serological testing?

by  Tyler Cowen in

I would like to know more, but here is one new paper on the topic, by Lottie Brown, et.al.:

Serological testing is emerging as a powerful tool to progress our understanding of COVID-19 exposure, transmission and immune response. Large-scale testing is limited by the need for in-person blood collection by staff trained in venepuncture. Capillary blood self-sampling and postage to laboratories for analysis could provide a reliable alternative. Two-hundred and nine matched venous and capillary blood samples were obtained from thirty nine participants and analysed using a COVID-19 IgG ELISA to detect antibodies against SARS-CoV-2. Thirty seven out of thirty eight participants were able to self-collect an adequate sample of capillary blood (≥50 μl). Using plasma from venous blood collected in lithium heparin as the reference standard, matched capillary blood samples, collected in lithium heparin-treated tubes and on filter paper as dried blood spots, achieved a Cohen′s kappa coefficient of >0.88 (near-perfect agreement). Storage of capillary blood at room temperature for up to 7 days post sampling did not affect concordance. Our results indicate that capillary blood self-sampling is a reliable and feasible alternative to venepuncture for serological assessment in COVID-19.

Via Alan Goldhammer.

Where do economics journal editors live and work?

by  Tyler Cowen in

Over half the journals we consider have over two thirds of their editorial power located in the USA. A large majority of journals have a tiny editorial contribution from academics located outside of North America and Europe. Any one of the states of California, Massachusetts and Illinois has more power than the four continents of Asia, South America, Africa and Australasia combined.

That is from a new paper by Simon D. Angus, Kadir Atalay, Jonathan Newton, and David Ubilava.  Here is a useful visual showing the actual distribution.

What is new in behavioral genetics?

by  Tyler Cowen in

Here is an excellent conceptual survey article by K. Paige Harden, it goes well beyond the usual.  Hard to summarize, but here are two good bits:

An early study using a DNA-based method estimated the heritability of height to be∼80%,and it noted that this result was “consistent with results from independent twin and family studies but using an entirely separate source of information” (Visscher et al. 2006). However, although the results from DNA-based method of estimating heritability scale with the estimates from twin and family studies, the former are typically smaller (Young et al. 2019). This discrepancy between heritability as estimated from classical twin and family studies and heritability as accounted for by measured DNA was labeled the missing heritability problem (Manolio et al. 2009). Recent work has suggested that some of the missing heritability is actually “hiding” in rare variants that are not typically measured and in the heterogeneity of genetic effects across populations (Tropfet al. 2017, Wainschtein et al. 2019, Young 2019). Whether missing or hiding, the continued gap between DNA-based estimates of heritability and estimates from twin/family studies means that the latter might still be overestimating heritability due to faulty assumptions. But it is no longer reasonable, contra some predictions, to expect that advances in human genomics will reveal that the heritability of psychological phenotypes is entirely illusory.

And this one:

In contrast to what is seen for educational attainment, most studies find a minimal effect of shared environmental factors on cognitive abilities, particularly when measured in adulthood. It has been suggested,however,that this near-zero main effect of the family-level environment masks the heterogeneity of the effects of the shared environment across the SES spectrum.An early paper by Turkheimer et al. (2003) analyzed data from a sample of twins with an unusual overrepresentation of children in poverty and found substantial effects of the shared environment on cognitive ability at age 7. Subsequent research on the genotype×SES interaction effect yielded mixed results, with several studies finding null effects or even effects in the opposite direction. However, a meta-analysis of this literature (Tucker-Drob & Bates 2016) found evidence of a significant interaction effect (albeit with a smaller effect size than estimated by Turkheimer and colleagues, an example of the winner’s curse), particularly in the United States.

The importance of the shared environment for cognitive ability has also been demonstrated us-ing adoption studies. In particular, population-wide data from Sweden allowed researchers to estimate the impact of the family environment using a unique sample of male-male sibling pairs where one brother was adopted while the other brother was raised by his biological parents (Kendler et al.2015). The IQ score of the adopted brother was, on average,∼4 points higher, an increase that varied with the education level of the adopting parents.

Recommended, interesting throughout, and worth a reread as well.  I have forgotten who sent it to me, if indeed anyone did, but I thank you.

Kiwi start-up to the Venus rescue

by  Tyler Cowen in

On Monday, scientists announced the astonishing discovery of phosphine in the atmosphere of Venus. This chemical could have been produced by a biological source, but scientists won’t know for sure without sending a spacecraft to the planet.

As luck would have it, Rocket Lab, the private small rocket company founded in New Zealand, has been working on such a mission. The company has developed a small satellite, called Photon, that it plans to launch on its own Electron rocket as soon as 2023.

“This mission is to go and see if we can find life,” said Peter Beck, Rocket Lab’s founder and chief executive. “Obviously, this discovery of phosphine really adds strength to that possibility. So I think we need to go and have a look there.”

Rocket Lab has launched a dozen rockets to space, putting small satellites into orbit for private companies, NASA and the U.S. military. It also has a mission to the moon in the works with NASA, called CAPSTONE, scheduled to launch in early 2021.

…The company’s plan is to develop the mission in-house and mostly self-fund it, at a cost in the tens of millions of dollars.

Here is the full NYT story by Jonathan O’Callaghan, interesting throughout.

Green vs. green: whose side are you on?

by  Tyler Cowen in

An Australian mining firm wants to turn a Nevada valley into a quarry for lithium and boron – key elements for green technologies – but a rare plant may stand in its way. Researchers say that biodiversity and clean energy should not be in opposition.

The company, Ioneer, says the quarry in Rhyolite Ridge valley would be the first US quarry of its kind, able to supply lithium for 400,000 electric car batteries a year and boron to power wind turbines. But soil containing these elements is also the perfect environment for Tiehm’s buckwheat (Eriogonum tiehmii), a plant that looks like a pile of leaves. When it blooms, it could be the dandelion’s fuzzy cousin.

There are only about 40,000 specimens of the buckwheat, and its namesake, Arnold Tiehm at the University of Nevada, Reno, says its closest relative is more than 80 kilometres away.

Most of the buckwheat’s natural home lies in the area mapped to be dug up for the quarry. “That puts the buckwheat on a one-way path to extinction,” says Patrick Donnelly at the Center for Biological Diversity (CBD) in Nevada. Ioneer will remove 65 per cent of the buckwheat’s population if the first planned quarry goes ahead, the company confirmed to New Scientist.

Although rare, the buckwheat isn’t yet considered endangered, but that may change. Following a petition by the CBD, the US Fish and Wildlife Service announced in July that the plant is both valuable enough and under sufficient threat to warrant a year-long review to decide whether to list the plant under the US Endangered Species Act. The listing would spell the end for the quarry as currently planned.

Here is the full story, via Ilya Novak.

Which economic methods are in practice statistically more honest than others?

by  Tyler Cowen in

…our results suggest that the [instrumental variables] and, to a lesser extent, [difference-in-difference] research bodies have substantially more p-hacking and/or selective publication than those based on [randomized controlled trials] and [regression-discontinuity]… (p.3)

And:

We find no evidence that: (1) Papers published in the ‘Top 5’ journals are different to others; (2) The journal ‘revise and resubmit’ process mitigates the problem; (3) Things are improving through time.

That is from this forthcoming AER paper by Brodeur, Cook, and Hayes.

In contrast, this blog post argues that:

I have proposed here that we should not infer that literatures with more bunching just past .05 are less trustworthy, and that visually striking comparisons of ‘expected’ and observed test results can be quite misleading due to incorrect assumptions about the expected line.

The authors respond here.  I do not yet have an opinion on this dispute, but everyone is talking about it right now, so I thought I would at least send along the basic documents to you all.

Declining Business Dynamism…The Role of the Burden of Knowledge

by  Tyler Cowen in

There is a new and important and I believe largely true paper from Thomas Astebro, Serguey Braguinsky, and Yuheng Ding:

We document that since 1997, the rate of startup formation has precipitously declined for firms operated by U.S. PhD recipients in science and engineering. These are supposedly the source of some of our best new technological and business opportunities. We link this to an increasing burden of knowledge by documenting a long-term earnings decline by founders, especially less experienced founders, greater work complexity in R&D, and more administrative work. The results suggest that established firms are better positioned to cope with the increasing burden of knowledge, in particular through the design of knowledge hierarchies, explaining why new firm entry has declined for high-tech, high-opportunity startups.

Here is the link.

Evidence from 27 Thousand Economics Journal Articles on Africa

by  Tyler Cowen in

The first two decades of the 21st century have seen an increasing number of peer-reviewed journal articles on the 54 countries of Africa by both African and non-African economists. I document that the distribution of research across African countries is highly uneven: 45% of all economics journal articles and 65% of articles in the top five economics journals are about five countries accounting for just 16% of the continent’s population. I show that 91% of the variation in the number of articles across countries can be explained by a peacefulness index, the number of international tourist arrivals, having English as an official language, and population. The majority of research is context-specific, so the continued lack of research on many African countries means that the evidence base for local policy-makers is much smaller in these countries.

Here is the article by Obie Porteus, via David Evans.

My Conversation with Matt Yglesias

by  Tyler Cowen in

Substantive, interesting, and fun throughout, here is the audio, video, and transcript.  For more do buy Matt’s new book One Billion Americans: The Case for Thinking Bigger.  Here is the CWT summary:

They discussed why it’s easier to grow Tokyo than New York City, the governance issues of increasing urban populations, what Tyler got right about pro-immigration arguments, how to respond to declining fertility rates, why he’d be happy to see more people going to church (even though he’s not religious), why liberals and conservatives should take marriage incentive programs more seriously, what larger families would mean for feminism, why people should read Robert Nozick, whether the YIMBY movement will be weakened by COVID-19, how New York City will bounce back, why he’s long on Minneapolis, how to address constitutional ruptures, how to attract more competent people to state and local governments, what he’s learned growing up in a family full of economists, his mother’s wisdom about visual design and more.

Here is one excerpt:

It was so much fun we even ran over the allotted time, we had to discuss Gilbert Arenas too.