Category: Medicine
It’s Time to Build the Peptidome!
ML needs data. Google’s AlphaGo trained on 30 million moves from human games and orders of magnitude more from games it played against itself. The largest language models are trained on at least 60 terabytes of text. AlphaFold was trained on just over 100,000 3D protein structures from the Protein Data Bank.
The data available for antimicrobial peptides is nowhere near these benchmarks. Some databases contain a few thousand peptides each, but they are scattered, unstandardized, incomplete, and often duplicative. Data on a few thousand peptide sequences and a scattershot view of their biological properties are simply not sufficient to get accurate ML predictions for a system as complex as protein-chemical reactions. For example, the APD3 database is small, with just under 4,000 sequences, but it is among the most tightly curated and detailed. However, most of the sequences available are from frogs or amphibians due to path-dependent discovery of peptides in that taxon. Another database, CAMPR4, has on the order of 20,000 sequences, but around half are “predicted” or synthetic peptides that may not have experimental validation, and contain less info about source and activity. The formatting of each of these sources is different, so it’s not easy to put all the sequences into one model. More inconsistencies and idiosyncrasies stack up for the dozens of other datasets available.
There is even less negative training data; that is, data on all the amino-acid sequences without interesting publishable properties. In current ML research, labs will test dozens or even hundreds of peptide sequences for activity against certain pathogens, but they usually only publish and upload the sequences that worked.
…The data problem facing peptide research is solvable with targeted investments in data infrastructure. We can make a million-peptide database
There are no significant scientific barriers to generating a 1,000x or 10,000x larger peptide dataset. Several high-throughput testing methods have been successfully demonstrated, with some screening as many as 800,000 peptide sequences and nearly doubling the number of unique antimicrobial peptides reported in publicly available databases. These methods will need to be scaled up, not only by testing more peptides, but also by testing them against different bacteria, checking for human toxicity, and testing other chemical properties, but scaling is an infrastructure problem, not a scientific one.
This strategy of targeted data infrastructure investments has three successful precedents: PubChem, the Human Genome Project, and ProteinDB.
Much more in this excellent piece of science and economics from IFP and Max Tabarrok.
Milei Implements Peer Approval for Food
Reason: In a sweeping move to overhaul Argentina’s food trade policies, Javier Milei’s administration officially deregulated food imports and exports on Monday. The reform, outlined in Decree 35/2025, seeks to boost foreign trade, cut bureaucratic red tape, and lower consumer prices.
Federico Sturzenegger, head of the Ministry of Deregulation and State Transformation, explained in a post on X that the measure “seeks cheaper food for Argentines and more Argentine food for the world.”
Under the new policy, food products and packaging certified by countries with “high sanitary surveillance” can now enter Argentina without any additional registration or approval processes. These items will be automatically recognized under the Argentine Food Code, cutting down on administrative delays and costs for importers.
The legislation identifies countries such as Australia, New Zealand, Canada, the United States, Israel, Japan, Switzerland, and the United Kingdom, as well as the European Union, as having similar or higher sanitary standards than Argentina.
As Sturzenegger explains in his post, this measure “eliminates requirements to register and authorize: samples, products, establishments, warehouses, utensils, and containers (32 pages of paperwork).”
An excellent “peer approval” policy and one that I have long supported when it comes to the FDA and drug approvals. In fact, since 2010 the US FDA has begun to recognize other countries as having comparable food safety systems. To date, Canada, Australia and New Zealand have been recognized with a Systems Recognition partnership.
Systems Recognition (SR) is a partnership between the U.S. Food and Drug Administration (FDA) and a foreign regulatory counterpart, in which the agencies have concluded that they operate comparable regulatory programs that yield similar food safety outcomes.
Argentina’s policy is unilateral and assumes equivalence if a country uses recognized standards (e.g., Codex Alimentarius) or has high sanitary vigilance while the FDA’s SR policy is bilateral and involves more regulatory harmonization and investigation. I prefer the Argentinian approach. Nevertheless, both programs have the goals of simplifying trade, avoiding duplicate inspections, and helping to prioritize scarce inspection resources.
I encourage the FDA to build on SR for food and extend it to drugs. This could be done in a minor and major way, both of which would useful. The minor reform would be peer approval for already-approved US drugs. In this way, importation could ease drug shortages. The FDA has done this in the past on an ad-hoc basis but it should be made permanent. The second, more major reform, would to extend peer-approval to any drug or device approved by a stringent authority.
What should I ask Theodore H. Schwartz?
Yes I will be doing a Conversation with him. He is a famous brain surgeon and author of the recent and excellent book Gray Matters: A Biography of Brain Surgery.
Here is his Wikipedia page, and an opening excerpt:
Theodore H. Schwartz (born May 13, 1965) is an American medical scientist, academic physician and neurosurgeon.
Schwartz specializes in surgery for brain tumors, pituitary tumors and epilepsy. He is particularly known for developing and expanding the field of minimally-invasive endonasal endoscopic skull base and pituitary surgery and for his research on neurovascular coupling and propagation of epilepsy.
Here is his home page. So what should I ask him?
The sick leave culture that is German
Germans are the “world champions in sick leave”, according to the head of the country’s biggest insurer, who was criticised for demanding that workers without a doctor’s note are unpaid for their first day off.
With the economy slowing and the welfare system under pressure, Germany can ill afford its average per worker of 20 sick days a year, said Oliver Bäte, the chief executive of Allianz SE. The EU average is eight.
The figure of 20 days, based on research by the health insurer DAK, puts a further dent in Germany’s ailing work ethic reputation. Last April, Christian Lindner, then finance minister, admitted that the French, Italians and other nationalities worked “a lot more than we do”, after OECD data showed Germans put in significantly fewer working hours per year than their EU and British neighbours…
“In countries like Switzerland and Denmark people work a month longer per year on average — with comparable pay,” he pointed out.
Here is more from the Times of London. If you can get through the gate, you will see it is Mexico that is the work ethic country.
The Cows in the Coal Mine
I remain stunned at how poorly we are responding to the threat from H5N1. Our poor response to COVID was regrettable but perhaps understandable given the US hadn’t faced a major pandemic in decades. Having been through COVID, however, you would think that we would be primed. But no. Instead of acting aggressively to stop the spread in cows we took a gamble that avian flu would fizzle out. It didn’t. California dairy herds are now so awash in flu that California has declared a state of emergency. Hundreds of herds across the United States have been infected.
I don’t think we are getting a good picture of what is happening to the cows because we don’t like to look too closely at our food supply. But I reported in September what farmers were saying:
The cows were lethargic and didn’t move. Water consumption dropped from 40 gallons to 5 gallons a day. He gave his cows aspirin twice a day, increased the amount of water they were getting and gave injections of vitamins for three days.
Five percent of the herd had to be culled.
“They didn’t want to get up, they didn’t want to drink, and they got very dehydrated,” Brearley said, adding that his crew worked around the clock to treat nearly 300 cows twice a day. “There is no time to think about testing when it hits. You have to treat it. You have sick cows, and that’s our job is to take care of them.”
Here’s another report from a vet:
…the scale of the farmers’ efforts to treat the sick cows stunned him. They showed videos of systems they built to hydrate hundreds of cattle at once. In 14-hour shifts, dairy workers pumped gallons of electrolyte-rich fluids into ailing cows through metal tubes inserted into the esophagus.
“It was like watching a field hospital on an active battlefront treating hundreds of wounded soldiers,” he said.
Here’s Reuters:
Cows in California are dying at much higher rates from bird flu than in other affected states, industry and veterinary experts said, and some carcasses have been left rotting in the sun as rendering plants struggle to process all the dead animals.
…Infected herds in California are seeing mortality rates as high as 15% or 20%, compared to 2% in other states, said Keith Poulsen, a veterinarian and director of the Wisconsin Veterinary Diagnostic Laboratory who has researched bird flu.
The California Department of Food and Agriculture did not respond to questions about the mortality rate from bird flu.
Does this remind you of anything? Must we wait until the human morgues are overrun?
The case fatality rate for cows appears to be low but significant, perhaps 2%. A small number of pigs have also been infected. On the other hand, over 100 million chickens, turkeys and ducks have been killed or culled.
There have now been 66 cases in humans in the US. Moreover, the CDC reports that in at least one case the virus appears to have evolved within its human host to become more infectious. We don’t know that for sure but it’s not good news. Recall that in theory a single mutation will make the virus much more capable of infecting humans.
When I wrote on December 1 that A Bird Flu Pandemic Would Be One of the Most Foreseeable Catastrophes in History Manifold Markets was predicting a 9% probability of greater than 1 million US human cases in 2025. Today the prediction is at 20%.
Once again, we may get lucky and that is still the way to bet but only the weak rely on luck. Strong civilizations don’t pray for luck. They crush the bugs. So far, we are not doing that.
Happy new year.
The New FDA and the Regulation of Laboratory Developed Tests
The FDA under President Trump and new FDA head Martin Makary should rapidly reverse the FDA’s powergrab on laboratory developed tests. To recap, laboratory developed tests (LDTs) are the kind your doctor orders, they are a service not a product and are not sold directly to patients. Congress has never given the FDA the authority to regulate LDTs. Indeed, in 2015, Paul Clement, the former US Solicitor General under George W. Bush, and Laurence Tribe, a leading liberal constitutional lawyer, wrote an article that rejected the FDA’s claims writing that the “FDA’s assertion of authority over laboratory-developed testing services is clearly foreclosed by the FDA’s own authorizing statute” and “by the broader statutory context.”
Moreover, in addition to legal reasons there are sound public policy reasons to reject FDA regulation of LDTs. Lab developed tests have never been FDA regulated, except briefly during the pandemic when the FDA used the declaration of emergency to issue so-called “guidance documents” saying that any SARS-COV-II test had to be pre-approved by the FDA. Thus, the FDA reversed the logic of emergency. In ordinary times, pre-approval was not necessary but when speed was of the essence it became necessary to get FDA pre-approval. The FDA’s pre-approval process slowed down testing in the United States and it wasn’t until after the FDA lifted its restrictions in March that tests from the big labs became available.
In a remarkably prescient passage, Clement and Tribe (2015, p. 18) had warned of exactly this kind of delay:
The FDA approval process is protracted and not designed for the rapid clearance of tests. Many clinical laboratories track world trends regarding infectious diseases ranging from SARS to H1N1 and Avian Influenza. In these fast-moving, life-or-death situations, awaiting the development of manufactured test kits and the completion of FDA’s clearance procedures could entail potentially catastrophic delays, with disastrous consequences for patient care.
We are seeing the same kind of FDA-caused delay for tests for bird-flu.
Moreover, unlike some of the proposals associated with incoming HHS head Robert Kennedy, reversing the FDA on lab-developed tests has significant support from a wide-variety of experts. Here, for example, is the American Hospital Association:
…we strongly believe that the FDA should not apply its device regulations to hospital and health system LDTs. These tests are not devices; rather, they are diagnostic tools developed and used in the context of patient care. As such, regulating them using the device regulatory framework would have an unquestionably negative impact on patients’ access to essential testing. It would also disrupt medical innovation in a field demonstrating tremendous benefits to patients and providers.
The Trump administration has a number of options:
…the LDT Final Rule was promulgated in time to escape Congressional Review Act scrutiny; however, the executive branch and a Republican-controlled Congress have other tools to limit or vitiate FDA’s authority. These include, in no particular order:
The U.S. Department of Health and Human Services (HHS) could revoke the LDT Final Rule. The recission of a rule is treated the same as the promulgation of a new rule. If HHS revokes the final rule, the cases will likely be dismissed as moot. The timing of such action is uncertain at this time.
FDA could extend or revise its policies of enforcement discretion. LDTs are currently subject to FDA’s phaseout policy which has five stages, the last of which begins in May 2028. Specific categories of IVDs will continue under an enforcement discretion policy indefinitely as described in the preamble to the final rule. HHS could quickly issue such a revised policy or policies without prior public comment if it determines such policy meets the threshold in 21 CFR 10.115(g)(2).
Congress could act. With a Republican-controlled House and Senate to start the new Trump administration, there is a chance that efforts to legislate the regulation of LDTs could be reignited. Based on prior congressional efforts, it is likely that such legislation would place LDTs under control by CMS and CLIA, rather than require LDTs to comply with FDA requirements.
HHS could let the litigation continue. The new administration may view the U.S. District Court for the Eastern District of Texas to be sympathetic to the Plaintiffs’ arguments and therefore proceed unabridged assuming the final rule will be struck-down, if that is indeed the deregulatory objective of the new administration.
The U.S. Department of Justice (DOJ) could act concerning the litigation. DOJ options are constrained by ethics rules but DOJ could request to amend its filings, pause the case pending rule-making proceedings, or take other actions intended to stall or moot the litigation in a deregulatory fashion.
Health insurance companies are not the main villain
First of all, insurance companies just don’t make that much profit. UnitedHealth Group, the company of which Brian Thompson’s UnitedHealthcare is a subsidiary, is the most valuable private health insurer in the country in terms of market capitalization, and the one with the largest market share. Its net profit margin is just 6.11%…
That’s only about half of the average profit margin of companies in the S&P 500. And other big insurers are even less profitable. Elevance Health, the second-biggest, has a margin of between 2% and 4%. Centene’s margin is usually around 1% to 2%. Cigna Group’s margin is usually around 2% to 3%. And so on. These companies are just making very little profit at all.
And:
In other words, Americans’ much-hated private health insurers are paying a higher percent of the cost of Americans’ health care than the government insurance systems of Sweden and Denmark and the UK are paying. The only reason Americans’ bills are higher is that U.S. health care provision costs so much more in the first place.
And:
In fact, the Kaiser Family Foundation does detailed comparisons between U.S. health care spending and spending in other developed countries. And it has concluded that most of this excess spending comes from providers — from hospitals, pharma companies, doctors, nurses, tech suppliers, and so on…
Recommended, here is the full post.
You Have Been Warned
New paper in Science, A single mutation in bovine influenza H5N1 hemagglutinin switches specificity to human receptors. If that isn’t clear enough, here is the editor’s summary:
In 2021, a highly pathogenic influenza H5N1 clade 2.3.4.4b virus was detected in North America that is capable of infecting a diversity of avian species, marine mammals, and humans. In 2024, clade 2.3.4.4b virus spread widely in dairy cattle in the US, causing a few mild human cases, but retaining specificity for avian receptors. Historically, this virus has caused up to 30% fatality in humans, so Lin et al. performed a genetic and structural analysis of the mutations necessary to fully switch host receptor recognition. A single glutamic acid to leucine mutation at residue 226 of the virus hemagglutinin was sufficient to enact the change from avian to human specificity. In nature, the occurrence of this single mutation could be an indicator of human pandemic risk. —Caroline Ash
Time to stock up on Tamiflu and Xofluza.
Addendum: See also A Bird Flu Pandemic Would Be One of the Most Foreseeable Catastrophes in History
A Bird Flu Pandemic Would Be One of the Most Foreseeable Catastrophes in History
Zeynep Tufekci writing in the NYTimes hits the nail on the head:
The H5N1 avian flu, having mutated its way across species, is raging out of control among the nation’s cattle, infecting roughly a third of the dairy herds in California alone. Farmworkers have so far avoided tragedy, as the virus has not yet acquired the genetic tools to spread among humans. But seasonal flu will vastly increase the chances of that outcome. As the colder weather drives us all indoors to our poorly ventilated houses and workplaces, we will be undertaking an extraordinary gamble that the nation is in no way prepared for.
All that would be more than bad enough, but we face these threats gravely hobbled by the Biden administration’s failure — one might even say refusal — to respond adequately to this disease or to prepare us for viral outbreaks that may follow.
…Devastating influenza pandemics arise throughout the ages because the virus is always looking for a way in, shape shifting to jump among species in ever novel forms. Flu viruses have a special trick: If two different types infect the same host — a farmworker with regular flu who also gets H5N1 from a cow — they can swap whole segments of their RNA, potentially creating an entirely new and deadly virus that has the ability to spread among humans. It’s likely that the 1918 influenza pandemic, for example, started as a flu virus of avian origin that passed through a pig in eastern Kansas. From there it likely infected its first human victim before circling the globe on a deadly journey that killed more people than World War I.
And that’s why it’s such a tragedy that the Biden administration didn’t — or couldn’t — do everything necessary to snuff out the U.S. dairy cattle infection when the outbreak was smaller and easier to address.
Will there be a large outbreak among humans? Probably not. But a 9% probabability of a bad event warrants more than a shrug. Bad doesn’t have to be on the scale of COVID-bad to warrant precaution. The 2009 H1N1 flu pandemic, while relatively mild, infected about 61 million people in the U.S., leading to 274,000 hospitalizations, 12,400 deaths, and billions of dollars in economic costs.
H5N1 will likely pass us over—but only the weak rely on luck. Strong civilizations don’t pray for mercy from microbes; they crush them. Each new outbreak should leave us not relieved, but better armed, better trained and better prepared for nature’s next assault.
*Blind Spots: When Medicine Gets It Wrong, and What It Means for Our Health*
That is the new book by Marty Makary. Since Makary has been nominated to head the FDA, I am surprised this work is not receiving more attention.
In the book, Makary is sympathetic to HRT, skeptical about a lot of antibiotic use (microbiome issues), says it is fine to ingest the cholesterol in eggs, and he is critical of earlier attempts to separate mothers and their babies. He believes silicone breast implants got a bum rap, and thinks we have screwed up the treatment of peanut allergies. A common theme is that there is too much groupthink in modern medicine and medical research. He wonders if we should be suspicious of fluoride, in part because of microbiome issues. He briefly worries about the ingestion of microplastics. I would not say I have concrete views on these questions, but overall I came away from this book comfortable with him running the FDA, at least relative to past candidates. I am skeptical of his views on fluoride, however, as the recent flurry of debate seems to have settled on a “fluoride is a net benefit” side. I also worry a bit he is picking on some easy cases (e.g., separating mothers from their babies), and not going hard enough on the incentive problems in U.S. health care and its research communities.
Makary is not obviously an accelerationist. Most of all, he likes to avoid groupthink and give matters a further look. While such a view is hard to disagree with, it makes me nervous in a bureaucratic context. In reality, “groupthink” is how many things get approved as quickly as they do. Just how many public health debates are we supposed to be reopening here? Should that be the priority of the FDA? Or should speeding up clinical trials and lowering their cost be the emphasis?
When he thinks about FDA matters, is he willing to have questions of incentives arise first in his thoughts? If so, that would be a break from his writing career so far.
I also would be curious to know why he thinks “his sides of these debates” will, on the whole, avoid groupthink more than the status quo has done. Lemon-picking from the status quo, even if we agree with him on every point, does not clarify this all-important question. Groupthink stems from incentives, and what kind of better incentives will he build into the U.S. health care system? He does write about “common sense,” and making things “physician-centered,” both fine and well, but I don’t see either of those as answering my questions in a scalable manner.
Makary wanted to approve and accelerate the Johnson and Johnson vaccine, a good sign in my view. Still, on some issues he will, for my tastes, be insufficiently consequentialist (“go ahead and let them try!”) and too worried about “getting the science right” and “sampling more data.”
Marty has strong academic and research credentials, here is his Wikipedia page. Here is more on what he has done, all positives in my view:
Makary is a director on the board at Harrow, an ophthalmic pharmaceuticals company, and an adviser to Sidecar Health, an insurance provider that aims to lower customer costs by eliminating provider networks and drug formularies.
He’s also chief medical adviser to Nava, a benefits brokerage, and chief medical officer at Sesame, a cash-pay health service market that offers compounded semaglutide, Stat reported over the weekend, raising questions about how Makary will approach the GLP-1 shortage brouhaha should he be confirmed.
Sesame’s founder, David Goldhill, wrote a well-known piece in The Atlantic about his father’s death from a hospital-acquired infection that references a surgery checklist Makary helped develop to reduce errors and adverse events.
During the pandemic he called for universal masking and opposed vaccine mandates. He supported national lockdowns and called for “first doses first.” He also raised doubts about children needing two doses of the Covid vaccine. Rather than relitigate whether those are all the correct views or not, I will simply note he is not a deregulator per se. He donated to Obama in 2008.
Here is a recent Russ Roberts podcast with Makary.
Overall, I see only upsides from this pick. Nonetheless I also see a good chance he focuses on reform directions where I think the expected benefits are small. So I am not excited by this pick, at least not yet.
Jay Bhattacharya at the NIH
Trump has announced the appointment, so it is worth thinking through a few matters. While much of the chatter is about the Great Barrington Declaration, I would note that Bhattacharya has a history of focusing on the costs of obesity. So perhaps we can expect more research funding for better weight loss drugs, in addition to other relevant public health measures.
Bhattacharya also has researched the NIH itself (with Packalen), and here is one bit from that paper: “NIH’s propensity to fund projects that build on the most recent advances has declined over the last several decades. Thus, in this regard NIH funding has become more conservative despite initiatives to increase funding for innovative projects.”
I would expect it is a priority of his to switch more NIH funding into riskier bets, and that is all to the good. More broadly, his appointment can be seen as a slap in the face of the Fauci smug, satisfied, “do what I tell you” approach. That will delight many, myself included, but still the question remains of how to turn that into concrete advances in public health policy. Putting aside the possibility of another major pandemic coming around, that is not so easy to do.
My main worry is simply that NIH staff will not trust their new director. The problem is not so much GBD, which can be compartmentalized as a “political” stance, but rather the earlier claims that many more people had Covid early than we had thought, and that expected fatalities were going to be quite low, with a maximum of 40,000. We all make mistakes, the question is how those mistakes get processed. If you interrogate Perplexity it will report “Bhattacharya has not publicly acknowledged or confessed to these mistakes in his early predictions.” You don’t have to agree with Perplexity (though contrary cites are welcome!), rather it suffices to say that reflects a common perception of the scientific community. He also seemed to be pushing those low fatality estimates for longer than might have been considered appropriate. And that is indeed a problem for his tenure at the NIH.
The danger is simply that NIH staff will double down on risk aversion, and they may not so readily support any attempt to make the grants themselves riskier, or rooted in the greater discretion of program directors, a’la DARPA and the like. They will fear that their director will not sufficiently follow the evidence, or admit when mistakes are being made and reverse course. Even if you fully agree with GBD and the like, I hope you are able to see this as a relevant problem. Every institutional revolution requires supportive troops on the inside, even if they are only a minority.
I very much hope this works out well, but in the meantime that is my reservation.
Alcohol estimates
The number of deaths caused by alcohol-related diseases more than doubled among Americans between 1999 and 2020, according to new research. Alcohol was involved in nearly 50,000 deaths among adults ages 25 to 85 in 2020, up from just under 20,000 in 1999.
The increases were in all age groups. The biggest spike was observed among adults ages 25 to 34, whose fatality rate increased nearly fourfold between 1999 and 2020.
Women are still far less likely than men to die of an illness caused by alcohol, but they also experienced a steep surge, with rates rising 2.5-fold over 20 years.
The new study, published in The American Journal of Medicine, drew on data from the Centers for Disease Control and Prevention.
*Gray Matters*
The author is Theodore M. Schwartz and the subtitle of this excellent book is A Biography of Brain Surgery. Excerpt:
Whil there is no proven ideal age for a brain surgeon, let’s just say that during the first five years after residency, we are still getting our sea legs. Over time, as with any learned skill, a subtle transition occurs. Suddenly, surgeries seem to take less effort. Movements become second nature as wel enter what psychologist Mihaly Csikszentmihalyi called a “flow state,” where pursuit of a single goal creates a transcendental state of purposeful concentration the task.
…One well-known neurosurgeon was once asked how he became so good at his craft. His answer? “there’s a graveyard full of my mistakes behind the hospital.”
Definitely recommended, the book also offers considerable detailed information about how brain surgery is done, which maladies lie behind brain surgery, and much more.
Human Challenge Trials Aren’t Riskier than RCTs
Nature: Keller Scholl got out of quarantine 13 days ago, and he’s still not feeling 100%. The itchiness — far and away the worst symptom, he says — is mostly gone, and now the graduate student just feels exhausted. “I’m trying to get enough sleep,” he says.
Scholl’s symptoms might be uncomfortable, but they are also of his own making. That’s because he signed up to be a volunteer in the first human ‘challenge trial’ involving Zika virus, a mosquito-borne pathogen that can cause fever, pain and, in some cases, a brain-development problem in infants. In standard infectious-disease trials, researchers test drugs or vaccines on people who already have, or might catch, a disease. But in challenge trials, healthy people agree to become infected with a pathogen so that scientists can gather preliminary data on possible drugs and vaccines before bigger trials take place. “Accelerating a Zika vaccine by a month, a few days, that does a lot of good in the world,” says Scholl, who studies at Pardee RAND Graduate School in Santa Monica, California.
Keller spent time here at GMU working with Robin Hanson and hanging out with the lunch gang. Way to go Keller! Thank you!
The rest of the article uncritically repeats the usual claims from so-called “bioethicists” that human challenge trials (HCTs) are unethical because they involve risks. Of course, HCTs carry risks—so what? Randomized controlled trials (RCTs) also require that participants are exposed to risk. Indeed, for participants in the placebo arm of an RCT, the risks are identical. Furthermore, since RCTs require more participants to achieve statistical validity than HCTs, they must expose more people to harm and, as a result, it’s even possible that more participants are harmed in an RCT than an HCT. Thus, HCTs are not necessarily more risky to participants than RCTs and, of course, to the extent that they speed up results, they can save many lives and greatly reduce risk to everyone else in the the larger society.
In my talk, The Economic Way of Thinking in a Pandemic (starting around 10:52, though the entire presentation is worthwhile), I explain the real reason why bioethicists and physicians hesitate over human challenge trials: they fear feeling personally responsible if a participant is harmed. “We exposed this person to risk, and they died.” Well, yes. But my response is, it’s not about you! Set aside personal emotions and focus on what saves the most lives.
Hat tip: Alexander Berger who pointed to this story that I had missed earlier.
The economic powers of the HHS secretary
That is the topic of my latest Bloomberg column, here is one excerpt:
One of the problems with an RFK Jr. ascendancy is that his core views, which run strongly against vaccines and pharmaceuticals, make it unlikely that any of these reimbursement revisions will be done in a rational or scientific way. The best evidence indicates that pharmaceuticals are a relatively cost-effective ways of saving lives, and conversely that many costly surgical procedures are not very effective. One of the main drawbacks of the US health-care system is often described as overtreatment, yet some vaccines and drugs — the Covid vaccines, GLP-1 medications and HIV-AIDS treatments, to name just a few — are yielding very high returns.
The danger is that, with RFK Jr. at HHS, the US would restrain health-care spending in exactly the wrong areas. The human costs of such a mistake are obvious, but from a more narrow fiscal perspective, a sicker America would lead to even more serious budgetary problems.
In any case, for all the recent talk and speculation about DOGE, the HHS secretary could well have more of an impact on the federal budget, for better or worse.
HHS also oversees liability protection for vaccines…
Worth a very serious ponder.