Sunday assorted links
1. Julia Steinberg on Solano County.
2. Mentorship advice from Avital Balwit.
3. Orcas are attacking boats in coordinated fashion. And more.
4. James Brown, Night Train, live.
6. Why don’t people return their shopping carts? (Often I am not sure it is my obligation to? In that context non-return might be Coasean.)
7. From Eliezer.
Why are US Clinical Trials so Expensive?
Dave Ricks, CEO of Eli Lilly, speaking on the excellent Cheeky Pint Podcast (hosted by John Collison, sometimes joined by Patrick as in this episode) had the clearest discussion of why US clinical trial costs are so expensive that I have read.
One point is obvious once you hear it: Sponsors must provide high-end care to trial participants–thus because U.S. health care is expensive, US clinical trials are expensive. Clinical trial costs are lower in other countries because health care costs are lower in other countries but a surprising consequence is that it’s also easier to recruit patients in other countries because sponsors can offer them care that’s clearly better than what they normally receive. In the US, baseline care is already so good, at least at major hospital centers where you want to run clinical trials, that it’s more difficult to recruit patients. Add in IRB friction and other recruitment problems, and U.S. trial costs climb fast.
Patrick
I looked at the numbers. So, apparently the median clinical trial enrollee now costs $40,000. The median US wage is $60,000, so we’re talking two thirds. Why and why couldn’t it be a 10th or a hundredth of what it is?David (00:10:50):
Yeah, brilliant question and one we’ve spent a lot of time working on…“Why does a trial cost so much?” Well, we’re taking the sickest slice of the healthcare system that are costing the most. And we’re ingesting them. We’re taking them out of the healthcare system and putting them in a clinical trial. Typically we pay for all care. So we are literally running the healthcare system for those individuals and that is in some ways for control, because you want to have the best standard of care so your experiment is properly conducted and it’s not just left to the whims of hundreds of individual doctors and people in Ireland versus the US getting different background therapies. So you standardize that, that costs money because sort of leveling up a lot of things, but then also in some ways you’re paying a premium to both get the treating physicians and have great care to get the patient. We don’t offer them remuneration, but they get great care and inducement to be in the study because you’re subjecting yourself quite often, not all the case, but to something other than the standard of care, either placebo or this. Or, in more specialized care, often it’s standard care plus X where X could actually be doing harm, not good. So people have to go into that in a blinded way and I guess the consideration is you’ll get the best care.Patrick (00:12:51):
Of the $40,000. How much of that should I look at as inducement and encouragement for the patient and how much should I look at it as the cost of doing things given the regulatory apparatus that exists?David (00:13:02):
The patient part is the level up part and I would say 20, 30% of the cost of studies typically would be this. So you’re buying the best standard of care, you’re not getting something less. That’s medicine costs, you’re getting more testing, you’re getting more visits, and then there is a premium that goes to institutions, not usually to the physician, the institution to pay for the time of everybody involved in it plus something. We read a lot about it in the NIH cuts, the 60% Harvard markup or whatever. There’s something like that in all clinical trials too. Overhead coverage, whatnot. But it’s paying for things that aren’t in the trial.Patrick (00:13:40):
US healthcare is famously the most expensive in the world. Yes. Do you run trials outside the US?David (00:13:44):
Yeah, actually most. I mean we want to actually do more in the US. This is a problem I think for our country. Take cancer care where you think, okay, what’s the one thing the US system’s really good at? If I had cancer, I’d come to the US, that’s definitely true. But only 4% of patients who have cancer in the US are in clinical trials. Whereas in Spain and Australia it’s over 25%.And some of that is because they’ve optimized the system so it’s easier to run and then enroll, which I’d like to get to, people in the trials. But some of it is also that the background of care isn’t as good. So that level up inducement is better for the patient and the physician. Here, the standard’s pretty good, so people are like, “Do I want to do something where there’s extra visits and travel time?” There’s another problem in the US which is, we have really good standards of care but also quite different performing systems and we often want to place our trials in the best performing systems that are famous, like MD Anderson or the Brigham. And those are the most congested with trials and therefore they’re the slowest and most expensive. So there’s a bit of a competition for place that goes on as well.
But overall, I would say in our diabetes and cardiovascular trials, many, many more patients are in our trials outside the US than in and that really shouldn’t be other than cost of the system. And to some degree the tuning of the system, like I mentioned with Spain and Australia toward doing more clinical trials. For instance, here in the US, everywhere you get ethics clearance, we call it IRB. The US has a decentralized system, so you have to go to every system you’re doing a study in. Some countries like Australia have a single system, so you just have one stop and then the whole country is available to recruit those types of things.
Patrick (00:15:31):
You said you want to talk about enrollment?David (00:15:32):
Yeah, yeah. It’s fascinating. So drug development time in the industry is about 10 years in the clinic, a little less right now. We’re running a little less than seven at Lilly, so that’s the optimization I spoke about. But actually, half of that seven is we have a protocol open, that means it’s an experiment we want to run. We have sites trained, they’re waiting for patients to walk in their door and to propose, “Would you like to be in the study?” But we don’t have enough people in the study. So you’re in the serial process, diffuse serial process, waiting for people to show up. You think, “Wow, that seems like we could do better than that. If Taylor Swift can sell at a concert in a few seconds, why can’t I fill an Alzheimer’s study? There seem to be lots of patients.” But that’s healthcare. It’s very tough. We’ve done some interesting things recently to work around that. One thing that’s an idea that partially works now is culling existing databases and contacting patients.Patrick (00:16:27):
Proactive outreach.
See also Chertman and Teslo at IFP who have a lot of excellent material on clinical trial abundance.
Lots of other interesting material in this episode including how Eli Lilly Direct—driven largely by Zepbound—has quickly become a huge pharmacy. The direct-to-consumer model it represents could be highly productive as more drugs for preventing disease are developed. I am not as anti-PBM as Ricks and almost everyone in the industry are but I will leave that for another day.
Here is the Cheeky Pint Podcast main page.
Best fiction of 2025
Solvej Balle, On the Calculation of Volume I, Volume II. Volume III is due out in English late this year I have read it already in German. A very strong series, reading ahead in German is a good demonstration of how much I like them.
Suat Dervis, The Prisoner of Ankara. A Turkish novel from mid-century, in English for the first time.
Emmanuel Carrere, V13: Chronicle of a Trial. Non-fiction but it is more likely reading fiction, it just happens to be true (supposedly).
Alain Mabanckou, Dealing with the Dead. Most African fiction does not connect with me, and there is a tendency for the reviews to be untrustworthy. This “cemetery memoir,” from the Congo (via UCLA), held my interest throughout.
Kiran Desai, The Loneliness of Sonia and Sunny.
Eça de Queiros, Adam and Eve in Paradise. Originally from the 19th century, but translated into English only this year. A 60 pp. novella about exactly what the title indicates, noting that matters are not as simple as the first telling of that story might have suggested.
The Poems of Seamus Heaney. Not yet received, but obviously this is a winner.
Overall, the Balle, Desai, and Heaney make for very strong entries, so this was a good year for fiction.
Emergent Ventures winners 48th cohort
Minh Nguyen, Dallas, 16, to address problems of space debris.
Serena Chen and Valerie Wu, Taipei and Los Angeles, better blood transportation.
Griffin Li, Boston, 19, general career support, issues in market pricing on apps.
Jamie Croucher, London, for a new scientific society, Society for Technological Advancement.
Sri Anumakonda, Carnegie Mellon, robotic hands.
Ben James, London, lowering the price of electricity.
Lucio Aurelio Moreira Menezes, Fortaleza and Stanford, computational biology.
Lauren Gilbert, London, a progress-oriented magazine for the developing world?
Annika Baberwal, Dubai, 8th grade, helping race cars run faster.
Bernardo Melotti, Bologna/Stanford, equipment to speed biological advances.
Elyas Sepahi, London, mathematics and machine learning.
Harishvin Sashikumar, Vancouver, 17, brain interfaces.
The Effect of Video Watching on Children’s Skills
This paper documents video consumption among school-aged children in the U.S. and explores its impact on human capital development. Video watching is common across all segments of society, yet surprisingly little is known about its developmental consequences. With a bunching identification strategy, we find that an additional hour of daily video consumption has a negative impact on children’s noncognitive skills, with harmful effects on both internalizing behaviors (e.g., depression) and externalizing behaviors (e.g., social difficulties). We find a positive effect on math skills, though the effect on an aggregate measure of cognitive skills is smaller and not statistically significant. These findings are robust and largely stable across most demographics and different ways of measuring skills and video watching. We find evidence that for Hispanic children, video watching has positive effects on both cognitive and noncognitive skills—potentially reflecting its role in supporting cultural assimilation. Interestingly, the marginal effects of video watching remain relatively stable regardless of how much time children spend on the activity, with similar incremental impacts observed among those who watch very little and those who watch for many hours.
That is from a new NBER working paper by
Saturday assorted links
1. John Brennan clarifies on UAPs.
2. “For the rest of the world, including Europe, wide adoption of US dollar stablecoins for payment purposes would be equivalent to the privatization of seigniorage by global actors,” notes Hélène Rey, an economist, who fears rising “tax evasion” and “lower demand for non-US government bonds”. FT link here.
3. “Puffins have been seen on the Isle of Muck in County Antrim for the first time in years, after a major scheme to remove invasive brown rats.” Link here.
5. Is there some economic recovery in Nigeria?
6. Charles Murray on finding religion.
7. Ross Douthat with Paul Kingsnorth (NYT).
The spatial construction of Incan monies?
Money can be many things, but this to me is a new one. Or is it?
Stretching for 1.5km and consisting of approximately 5200 precisely aligned holes, Monte Sierpe in southern Peru is a remarkable construction that likely dates to at least the Late Intermediate Period (AD 1000–1400) and saw continued use by the Inca (AD 1400–1532). Yet its function remains uncertain. Here, the authors report on new analyses of drone imagery and sediment samples that reveal numerical patterns in layout, potential parallels with Inca knotted-string records and the presence of crops and wild plants. All this, the authors argue, suggests that Monte Sierpe functioned as a local, Indigenous system of accounting and exchange.
That is newly published research from Jacob L. Bongers, et.al. Via the excellent Kevin Lewis.
Was Brexit worse than we had thought?
This paper examines the impact of the UK’s decision to leave the European Union (Brexit) in 2016. Using almost a decade of data since the referendum, we combine simulations based on macro data with estimates derived from micro data collected through our Decision Maker Panel survey. These estimates suggest that by 2025, Brexit had reduced UK GDP by 6% to 8%, with the impact accumulating gradually over time. We estimate that investment was reduced by between 12% and 18%, employment by 3% to 4% and productivity by 3% to 4%. These large negative impacts reflect a combination of elevated uncertainty, reduced demand, diverted management time, and increased misallocation of resources from a protracted Brexit process. Comparing these with contemporary forecasts – providing a rare macro example to complement the burgeoning micro-literature of social science predictions – shows that these forecasts were accurate over a 5-year horizon, but they underestimated the impact over a decade.
That is from a new NBER working paper by
*The Science of Second Chances*
The author is economist Jennifer Doleac, and the subtitle is A Revolution in Criminal Justice. Excerpt:
We found that adding anyone charged with a felony to the law enforcement DNA database in Denmark reduced future criminal convictions by over 40 percent. Again, people responded to the higher probability of getting caught by committing fewer crimes. Being added to the database also increased enrollment in school and rates of employment — signs that folks really were on a better path. This effect was largest for the youngest men, those ages eighteen to twenty-four.
Incentives matter. An excellent book, recommended, due out next year.
Friday assorted links
1. Coetzee started as a programmer.
2. How is the Norwegian wealth tax working out?
3. Netta Engelhardt talk on the black hole information paradox. I think of it as a talk on faster than light travel.
4. Did prisons just replace mental hospitals?
5. “Date me” doc from a highly intelligent and aesthetic woman.
“Some Economics of Artificial Super Intelligence”
I promised to pass along serious models of pending AI doom, especially if they are peer-reviewed or at least headed for such. The AI doomer types still are dropping the ball on this, but one economist has made a contribution and so here it is from Henry A. Thompson:
Conventional wisdom holds that a misaligned artificial superintelligence (ASI) will destroy humanity. But the problem of constraining a powerful agent is not new. I apply classic economic logic of interjurisdictional competition, all-encompassing interest, and trading on credit to the threat of misaligned ASI. Using a simple model, I show that an acquisitive ASI refrains from full predation under surprisingly weak conditions. When humans can flee to rivals, inter-ASI competition creates a market that tempers predation. When trapped by a monopolist ASI, its “encompassing interest” in humanity’s output makes it a rational autocrat rather than a ravager. And when the ASI has no long-term stake, our ability to withhold future output incentivizes it to trade on credit rather than steal. In each extension, humanity’s welfare progressively worsens. But each case suggests that catastrophe is not a foregone conclusion. The dismal science, ironically, offers an optimistic take on our superintelligent future.
You may or may not agree, but as usual the point is to build out a literature, not to regard any single paper as the final word. Via the excellent Joy Buchanan.
My first trip to Tokyo
To continue with the biographical segments:
My first trip to Tokyo was in 1992. I was living in New Zealand at the time, and my friend Dan Klein contacted me and said “Hey, I have a work trip to Tokyo, do you want to meet me there?” And so I was off, even though the flight was more of a drag than I had been expecting. It is a long way up the Pacific.
Narita airport I found baffling, and it was basically a two hour, multi-transfer trip to central Tokyo. Fortunately, a Japanese woman was able to help us make the connections. I am glad these days that the main flights come into Haneda.
(One Japan trip, right before pandemic, I decided to spend a whole day in Narita proper. Definitely recommended for its weirdness. Raw chicken was served in the restaurants, and it felt like a ghost town except for some of the derelicts in the streets. This experience showed me another side of Japan.)
We stayed in a business hotel in Ikebukuro, a densely populated but not especially glamorous part of Tokyo. It turned out that was a good way to master the subway system and also to get a good sense of how Tokyo was organized. I had to one-shot memorize the rather complicated footpath from the main subway station to the hotel, which had been chosen by my friend’s sponsors. As we first emerged from the subway station, we had, getting there the first time, to ask two Japanese high schoolers to help us find the way. They spoke only a few words of English, but we showed them the address in Japanese and they even carried our bags for us, grunting “Hai!” along the way, giving us a very Japanese experience.
In those days very little English was spoken in Tokyo, especially outside a few major areas such as Ginza. You were basically on your own.
I recall visiting the Sony Center, which at the time was considered the place to go to see new developments in “tech.” I marveled at the 3-D TV, and realized we had nothing like it. I felt like I was glimpsing the future, but little did I know the technology was not going anywhere. Nor for that matter was the company. Here is Noah, wanting the Japanese future back.
Most of all, Tokyo was an extreme marvel to me. I felt it was the single best and most interesting place I had visited. Everywhere I looked — even Ikebukuro — there was something interesting to take note of. The plastic displays of food in the windows (now on the way out, sadly) fascinated me. The diversity, order, and package wrapping sensibilities of the department stores were amazing. The underground cities in the subways had to be seen to be believed (just try emerging from Shinjuku station and finding the right exit). The level of dress and stylishness and sophistication was extreme, noting I would not say the same about Tokyo today. This was not long after the bubble had burst, but the city still had the feel of prosperity. Everything seemed young and dynamic.
I also found Tokyo affordable. The reports of the $2,000 melon were true, but the actual things you would buy were somewhat cheaper than in say New York City. It was easy to get an excellent meal for ten dollars, and without much effort. My hotel room was $50 a night. The subway was cheap, and basically you could walk around and look at things for free. The National Museum was amazing, one of the best in the world and its art treasures cannot, in other forms, readily be seen elsewhere.
Much as I like Japanese food, I learned during this trip that I cannot eat it many meals in a row. This was the journey where I realized Indian food (!) is my true comfort food. Tokyo of course has (and had) excellent Indian food, just as it has excellent food of virtually every sort. I learned a new kind of Chinese food as well.
The summer heat did not bother me. I also learned that Tokyo is one of the few cities that is better and more attractive at night.
I recall wanting to buy a plastic Godzilla toy. I walked around the proper part of town, and kept on asking for Godzilla. I could not figure out why everyone was staring at me like I was an idiot, learning only later that the Japanese say “Gojira.” So in a pique of frustration, I did my best fire-breathing, stomping around, “sound like a gorilla cry run backwards through the tape” imitation of Godzilla. Immediately a Japanese man excitedly grabbed me by the hand, walked me through some complicated market streets, and showed me where I could buy a Godzilla, shouting “Gojira, Gojira, Gojira!” the whole time.
I came away happy.
My side trip, by the way, was to the shrines and temples of Kamakura, no more than an hour away but representing another world entirely. Recommended to any of you who are in Tokyo with a day to spare.
Now since that time, I’ve never had another Tokyo trip quite like that one. These days, and for quite a while, the city feels pretty normal to me, rather than like visiting the moon. Fluent English is hard to come by, but most people can speak some English and respond to queries. You can translate and get around using GPS, AI, and so on. The city is much more globalized, and other places have borrowed from its virtues as well.
Looking back, I am very glad I visited Tokyo in 1992. The lesson is that you can in fact do time travel. You do it by going to some key places right now.
Markets in everything?
Wealthy foreign gun enthusiasts paid Bosnian Serb forces for the chance to shoot residents of Sarajevo during the siege of the city during the 1990s, according to claims being investigated by Italian magistrates.
The investigation was prompted by new evidence that “weekend snipers” paid handsomely to line the hills around Sarajevo and join in the Bosnian Serb siege, which killed more than 11,500 people between 1992 and 1996 during the Balkan Wars.
The investigation into the alleged “human safari” in Sarajevo has been opened after years of research by the Italian writer Ezio Gavazzeni, who said a key source was a former Bosnian intelligence officer.
“What I learnt is that Bosnian intelligence warned the local office of the Italian secret service … about the presence of at least five Italians who were taken to the hills above Sarajevo to shoot civilians,” he told the Italian daily La Repubblica.
Here is more from the Times of London.
Thursday assorted links
2. John Cochrane on causal identification.
3. What are the density trends in major cities around the world?
4. “You Can Now Invest In A Hedge Fund Dedicated To Hermès Bags.”
5. What does it mean for an experiment to be beautiful?
8. New Yorker fact checkers confirm that AI song really did hit #1 on the C&W charts.
9. Here is the 5.1 Thinking model on different kinds of humor in Woody Allen movies, and then a follow-up question on the influence of Bergman. Impressive, as is the model more generally.
Waymo
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