The Elephant in the Brain: Hidden Motives in Everyday Life, and here is the opening bit of the summary:

Human beings are primates, and primates are political animals. Our brains were designed not just to gather and hunt, but also to get ahead socially, often by devious means. The problem is that we like to pretend otherwise; we’re afraid to acknowledge the extent of our own selfishness. And this makes it hard for us to think clearly about ourselves and our behavior.

The Elephant in the Brain aims to fix this introspective blind spot by blasting floodlights into the dark corners of our minds. Only when everything is out in the open can we really begin to understand ourselves: Why do humans laugh? Why are artists sexy? Why do people brag about travel? Why do we so often prefer to speak rather than listen?

Like all psychology books, The Elephant in the Brain examines many quirks of human cognition. But this book also ventures where others fear to tread: into social critique. The authors show how hidden selfish motives lie at the very heart of venerated institutions like Art, Education, Charity, Medicine, Politics, and Religion.

Acknowledging these hidden motives has the potential to upend the usual political debates and cast fatal doubt on many polite fictions. You won’t see yourself — or the world — the same after confronting the elephant in the brain.

Due out January 1, 2018, of course this is essential reading.

For years, muscular dystrophy patients in the United States have been purchasing the drug deflazacort — used to stabilize muscle strength and keep patients mobile for a period of time — from companies in the United Kingdom at a manageable price of $1,600 a year.

But because an American company just got approval from the Food and Drug Administration to sell the drug in the United States, the price of the drug will soar to a staggering $89,000 annually, the Wall Street Journal reported last week.

Because the FDA restricts the importing of drugs from overseas if a version is available domestically, patients are stuck with the new, expensive version. This makes deflazacort the perfect case for advocates of international drug reciprocity — a reform that would make it easier for consumers to buy drugs that have been approved in other developed countries.

That is the introduction to an interview with yours truly in the Washington Post. I discuss thalidomide and the race to the bottom argument. Here is one other bit:

IT: Do you have any thoughts about the potential for FDA reform under this new administration and Congress?

AT: Peter Thiel’s speech at the Republican National Convention reminded us that we used to take big, bold risks — like going to the moon. Today, to say a project is a “moon shot” is almost a put-down, as if going to the moon never happened. We have become risk-averse and complacent, to borrow a term from my colleague Tyler Cowen. The result of the incessant focus on safety is playgrounds without teeter totters, armed guards at our schools and national monuments, infrastructure projects that no longer get built, and pharmaceutical breakthroughs that never happen.

The new administration is unpredictable, but when it comes to the FDA, unpredictable is better than business as usual.

The administration has yet to appoint a great FDA commissioner. Early names floated included Balaji Srinivasan, Jim O’Neill, Joseph Gulfo, and Scott Gottlieb but Srinivasan seems to have removed himself from the running. O’Neill would be great but I don’t think the US is ready, so that leaves Gulfo and Gottlieb. My suspicion is that Trump will like Gulfo because of Gulfo’s entrepreneurial experience but, as I said, the new administration is unpredictable.

I don’t have a similar graph for subway workers, but come on. The overall pictures is that health care and education costs have managed to increase by ten times without a single cent of the gains going to teachers, doctors, or nurses. Indeed these professions seem to have lost ground salary-wise relative to others.

That is just one bit from a very excellent blog post by Scott Alexander.

They have a new book out, namely Governing Global Health: Who Runs the World and Why?  It is to the point, clear, uses economic reasoning very well, and serves up the information you actually want to learn.  It is a look at some major public health organizations, specifically the Global Fund to Fight AIDS, TB and Malaria, the Gavi Alliance, the WHO, and the World Bank, and how they operate, from a public choice point of view.  It’s hard to think of many books I’ve looked at over the last year or two that so well understand the notion that readers want a “landscape” of sorts painted for them.  So if you have an interest in public health issues, or in either or both of the two authors, I can gladly recommend this to you.

Here is an earlier Chelsea Clinton memo on Haiti.

There is a new paper on this topic, by Gigi Moreno, Emma van Eijndhoven, Jennifer Benner, and Jeffrey Sullivan.  The upshot is to beware price controls:

Price controls for prescription drugs are once again at the forefront of policy discussions in the United States. Much of the focus has been on the potential short-term savings – in terms of lower spending – although evidence suggests price controls can dampen innovation and adversely affect long-term population health. This paper applies the Health Economics Medical Innovation Simulation, a microsimulation of older Americans, to estimate the long-term impacts of government price setting in Medicare Part D, using pricing in the Federal Veterans Health Administration program as a proxy. We find that VA-style pricing policies would save between $0.1 trillion and $0.3 trillion (US$2015) in lifetime drug spending for people born in 1949–2005. However, such savings come with social costs. After accounting for innovation spillovers, we find that price setting in Part D reduces the number of new drug introductions by as much as 25% relative to the status quo. As a result, life expectancy for the cohort born in 1991–1995 is reduced by almost 2 years relative to the status quo. Overall, we find that price controls would reduce lifetime welfare by $5.7 to $13.3 trillion (US$2015) for the US population born in 1949–2005.

I would insist that we do not have good enough models of the innovation process to really understand the price elasticity of supply.  Nonetheless it is surely not zero, and under plausible assumptions the price controls are a bad idea.

We need a new rooftop chant: “Beware analyses that neglect supply elasticities,” to sweet cadences of course.  They should play that on AM radio as well.

For the pointer I thank the still excellent Kevin Lewis.

A new study by the Taub Center for Social Policy Studies in Israel finds a relationship between the longevity of men in Israel and army service, which contributes to Israeli men’s better physical fitness

Main findings:

  • In 2013, the average life expectancy for men in Israel was 81 years, in contrast to the OECD average of 77.7 and a world average of 68.8 years.
  • Considering other variables that influence longevity – including wealth and education levels, the health system and the country’s general demographic profile – the Israeli advantage is large and increasing.
  • An analysis based on a sample of more than 130 countries found that military service added more than three years to male life expectancy.
  • This conclusion is reinforced in data showing the differences in the average life expectancy of men and women in Israel and in the OECD. In the 34 OECD countries, women live an average of 5.5 years longer than men, but in Israel, where military service is shorter and in most cases less physically demanding for women, women’s life expectancy is only 3 years longer.
  • While military service is an important component in public health, it has not yet been discussed in the academic literature on general health factors, nor has it been discussed in Israeli health literature.

Here is further information.  Here is a link to the cited report.  Here is the study itself.

I am very much against the draft outside of extreme military emergencies, but I suspect when the economic history of the American 20th century is written, the end of the draft will play some significant role in explaining the evolution of conditions for the deplorables.

For the pointer to this work I thank Rafi Bryl.

What accounts for misery?

by on January 27, 2017 at 2:20 am in Data Source, Medicine, Science | Permalink

Sarah Flèche and Richard Layard have a new paper on this topic, and they suggest a focus on mental illness:

Studies of deprivation usually ignore mental illness. This paper uses household panel data from the USA, Australia, Britain and Germany to broaden the analysis. We ask first how many of those in the lowest levels of life-satisfaction suffer from unemployment, poverty, physical ill health, and mental illness. The largest proportion suffers from mental illness. Multiple regression shows that mental illness is not highly correlated with poverty or unemployment, and that it contributes more to explaining the presence of misery than is explained by either poverty or unemployment. This holds both with and without fixed effects.

I don’t like the term “mental illness,” yet at the same time I reject the Szaszian rejection of the concept.  I would say that mental processes can deviate from procedural rationality in especially disadvantageous (and sometimes systematic) ways, and that this is something above and beyond merely having “different preferences.”

For the pointer I thank the excellent Kevin Lewis.

Frances Kelsey Syndrome

by on January 25, 2017 at 7:30 am in Economics, Law, Medicine | Permalink

Occasionally I have been told that FDA reform is something that only a few libertarian economists support. But in fact, there is strong support for reform in much of the medical community. See, for example, the survey that Dan Klein and I did on off-label prescribing and FDA reform or the many surveys of physicians done by CEI.

I mentioned Dr. Vincent DeVita in my post, Will Trump Appoint a Great FDA Commissioner? It’s worthwhile exploring DeVita’s views at greater length because he is a prominent figure in the field of oncology. Here, from Wikipedia, is some background on DeVita:

Vincent Theodore DeVita, Jr., MD is an internationally recognized pioneer physician in the field of oncology. DeVita spent the early part of his career at the National Cancer Institute (NCI). In 1980, the president of the United States appointed him as director of the NCI and the National Cancer Program, a position he held until 1988. While at the NCI, he was instrumental in developing combination chemotherapy programs that ultimately led to an effective regimen of curative chemotherapy for Hodgkin’s disease and diffuse large cell lymphomas. Along with colleagues at the NCI, he developed the four-drug combination, known by the acronym MOPP, which increased the cure rate for patients with advanced Hodgkin’s disease from nearly zero to over 70%.

DeVita was the Director of Yale Cancer Center from 1993 to 2003. He is currently the chair of the Yale Cancer Center advisory board and is professor of internal medicine and of epidemiology and public health at Yale’s medical school.

DeVita currently serves on the editorial boards of numerous scientific journals and is the author or co-author of more than 450 scientific articles. He is one of the three editors of the popular textbook (also available online) Cancer: Principles and Practice of Oncology and serves as the editor-in-chief of The Cancer Journal.

In his book, The Death of Cancer, DeVita has a chapter on the FDA. The title of that chapter? Frances Kelsey Syndrome. He writes:

The thalidomide episode sent the message to those who worked at the FDA that the way to do right by people was to say no. Saying yes would prove perilous–not only to patients, but to the careers of a reviewer. As a result, the agency tends to reward those who say no, not yes. (In fact, there’s an annual Frances Kelsey award. But there are no awards for getting a good drug quickly into the public domain.)

Exactly right. Later he discusses another problem that he sees with FDA evaluation procedures:

We are approaching what we might have considered nirvana years ago. We can design drugs that will hit a specific target, and by being so specific, they have fewer side effects. But because effective treatments almost always require hitting more than one target at the same time, some very good and relatively safe cancer drugs show no evidence of effectiveness when used alone.

What a dilemma. After spending millions of dollars developing a drug, a company may be forced to abandon it for lack of efficacy, when, if approved, it would be another exciting tool for clinical investigators who want to explore combinations of targeted therapies in post-market research trials. Compound that with the FDA’s insistence on testing them first on patients with very advanced, resistant disease, and many potentially useful drugs don’t look so good. As a result, drug companies are reluctant to invest money in new cancer drugs, because they might never make it past the FDA’s hurdles.

DeVita may be wrong but he’s certainly not uninformed.

DIY Gene Therapy

by on January 24, 2017 at 6:03 am in Economics, Law, Medicine, Uncategorized | Permalink

As I noted in yesterday’s post, Will Trump Appoint a Great FDA Commissioner?, personalized medicine is a challenge to the FDA. Technology Review has an excellent piece on an extreme version of personalized medicine, DIY gene therapy:

Hanley, 60, is the founder of a one-man company called Butterfly Sciences, also in Davis. After encountering little interest from investors for his ideas about using DNA injections to help strengthen AIDS patients, he determined that he should be the first to try it. “I wanted to prove it, I wanted to do it for myself, and I wanted to make progress,” says Hanley.

Most gene therapy involves high-tech, multimillion-dollar experiments carried out by large teams at top medical centers, with an eye to correcting rare illnesses like hemophilia. But Hanley showed that gene therapy can be also carried out on the cheap in the same setting as liposuction or a nose job, and might one day be easily accessed by anyone.

…Hanley opted instead for a simpler method called electroporation. In this procedure, circular rings of DNA, called plasmids, are passed into cells using an electrical current. Once inside, they don’t become a permanent part of person’s chromosomes. Instead, they float inside the nucleus. And if a gene is coded into the plasmid, it will start to manufacture proteins. The effect of plasmids is temporary, lasting weeks to a few months.

Hanley’s method is painful and doesn’t last long but it’s remarkable that it can be done at all.

At least one additional person who underwent self-administered gene therapy is a U.S. biotech executive who did not want his experience publicly known because he is dealing with the U.S. Food and Drug Administration on other matters.

Hanley says he did not secure the approval of the FDA before carrying out his experiment either. The agency requires companies to seek an authorization called an investigational new drug application, or IND, before administering any novel drug or gene therapy to people. “They said ‘You need an IND’ and I said, ‘No, I don’t,’” recalls Hanley, who traded e-mails with officials at the federal agency. He argued that self-experiments should be exempt, in part because they don’t pose any risk to the public.

Hat tip: Samir Varma.

As someone who has written about FDA reform for many years it’s gratifying that all of the people whose names have been floated for FDA Commissioner would be excellent, including Balaji Srinivasan, Jim O’Neill, Joseph Gulfo, and Scott Gottlieb. Each of these candidates understands two important facts about the FDA. First, that there is fundamental tradeoff–longer and larger clinical trials mean that the drugs that are approved are safer but at the price of increased drug lag and drug loss. Unsafe drugs create concrete deaths and palpable fear but drug lag and drug loss fill invisible graveyards. We need an FDA commissioner who sees the invisible graveyard.

Each of the leading candidates also understands that we are entering a new world of personalized medicine that will require changes in how the FDA approves medical devices and drugs. Today almost everyone carries in their pocket the processing power of a 1990s supercomputer. Smartphones equipped with sensors can monitor blood pressure, perform ECGs and even analyze DNA. Other devices being developed or available include contact lens that can track glucose levels and eye pressure, devices for monitoring and analyzing gait in real time and head bands that monitor and even adjust your brain waves.

The FDA has an inconsistent even schizophrenic attitude towards these new devices—some have been approved and yet at the same time the FDA has banned 23andMe and other direct-to-consumer genetic testing companies from offering some DNA tests because of “the risk that a test result may be used by a patient to self-manage”. To be sure, the FDA and other agencies have a role in ensuring that a device or test does what it says it does (the Theranos debacle shows the utility of that oversight). But the FDA should not be limiting the information that patients may discover about their own bodies or the advice that may be given based on that information. Interference of this kind violates the first amendment and the long-standing doctrine that the FDA does not control the practice of medicine.

Srinivisan is a computer scientist and electrical engineer who has also published in the New England Journal of Medicine, Nature Biotechnology, and Nature Reviews Genetics. He’s a co-founder of Counsyl, a genetic testing firm that now tests ~4% of all US births, so he understands the importance of the new world of personalized medicine.

The world of personalized medicine also impacts how new drugs and devices should be evaluated. The more we look at people and diseases the more we learn that both are radically heterogeneous. In the past, patients have been classified and drugs prescribed according to a handful of phenomenological characteristics such as age and gender and occasionally race or ethnic background. Today, however, genetic testing and on-the-fly examination of RNA transcripts, proteins, antibodies and metabolites can provide a more precise guide to the effect of pharmaceuticals in a particular person at a particular time.

Greater targeting is beneficial but as Peter Huber has emphasized it means that drug development becomes much less a question of does this drug work for the average patient and much more about, can we identify in this large group of people the subset who will benefit from the drug? If we stick to standard methods that means even larger and more expensive clinical trials and more drug lag and drug delay. Instead, personalized medicine suggests that we allow for more liberal approval decisions and improve our techniques for monitoring individual patients so that physicians can adjust prescribing in response to the body’s reaction. Give physicians a larger armory and let them decide which weapon is best for the task.

I also agree with Joseph Gulfo (writing with Briggeman and Roberts) that in an effort to be scientific the FDA has sometimes fallen victim to the fatal conceit. In particular, the ultimate goal of medical knowledge is increased life expectancy (and reducing morbidity) but that doesn’t mean that every drug should be evaluated on this basis. If a drug or device is safe and it shows activity against the disease as measured by symptoms, surrogate endpoints, biomarkers and so forth then it ought to be approved. It often happens, for example, that no single drug is a silver bullet but that combination therapies work well. But you don’t really discover combination therapies in FDA approved clinical trials–this requires the discovery process of medical practice. This is why Vincent DeVita, former director of the National Cancer Institute, writes in his excellent book, The Death of Cancer:

When you combine multidrug resistance and the Norton-Simon effect , the deck is stacked against any new drug. If the crude end point we look for is survival, it is not surprising that many new drugs seem ineffective. We need new ways to test new drugs in cancer patients, ways that allow testing at earlier stages of disease….

DeVita is correct. One of the reasons we see lots of trials for end-stage cancer, for example, is that you don’t have to wait long to count the dead. But no drug has ever been approved to prevent lung cancer (and only six have ever been approved to prevent any cancer) because the costs of running a clinical trial for long enough to count the dead are just too high to justify the expense. Preventing cancer would be better than trying to deal with it when it’s ravaging a body but we won’t get prevention trials without changing our standards of evaluation.

Jim O’Neill, managing director at Mithril Capital Management and a former HHS official, is an interesting candidate precisely because he also has an interest in regenerative medicine. With a greater understanding of how the body works we should be able to improve health and avoid disease rather than just treating disease but this will require new ways of thinking about drugs and evaluating them. A new and non-traditional head of the FDA could be just the thing to bring about the necessary change in mindset.

In addition, to these big ticket items there’s also a lot of simple changes that could be made at the FDA. Scott Alexander at Slate Star Codex has a superb post discussing reciprocity with Europe and Canada so we can get (at the very least) decent sunscreen and medicine for traveler’s diarrhea. Also, allowing any major pharmaceutical firm to produce any generic drug without going through a expensive approval process would be a relatively simply change that would shut down people like Martin Shkreli who exploit the regulatory morass for private gain.

The head of the FDA has tremendous power, literally the power of life and death. It’s exciting that we may get a new head of the FDA who understands both the peril and the promise of the position.

That is the topic of my latest Bloomberg column, here is one excerpt:

At a further margin, government’s contribution to the health care, retirement and education sectors will also seem inadequate, because at such high prices a government really cannot pay for everything. A heated political debate will ensue. Progressives will argue that significant human needs are being neglected, and they will be able to point to numerous supportive anecdotes. Conservatives will argue that the fiscal path behind such policies is unsustainable, and they will be right, too. Because it will feel to voters that government isn’t doing a good job in these high-cost areas, the conservative view will get further traction. Libertarians may promote radical spending cuts, hoping for much higher productivity growth, but the government interventions are built in so thickly that that strategy could take a long time to pay off, and in the meantime it won’t look like a political winner.

All of the various sides may be correct in their major claims, but none will have a workable solution. This actually isn’t so far from where the health-care debate stands now, and where the retirement and nursing home debate is headed as America ages.

Do read the whole thing.

As a simple rule, reject any argument that asserts “my opponent X is leaving a health care need unfilled” because indeed that is always the case.  Within Obamacare, for instance, do you favor expanding the scope of the mandate at every margin?  Probably not.  The trick is to have a good argument for why yours is the Goldilocks position, not to note that those who subsidize health care less are…doing less.  There is always someone who wants to subsidize more than you do, so fight Parfit’s “war on two fronts.”

I’ve been getting lots of vaccinations in preparation for my sabbatical in India. A Canadian friend recommended Dukoral. Dukoral is a vaccine for cholera, a very serious disease although one that’s rare for travelers even in undeveloped countries. (It’s roughly comparable in prevalence to Japanese encephalitis, however, which most travel physicians recommend vaccinating for.) As a side-effect, however, Dukoral is also quite effective (60%) against the most common cause of traveler’s diarrhea, that caused by enterotoxigenic E. coli.

Dukoral was approved in the European Union in 2004 but it has not been approved in the United States (a different cholera vaccine was approved late last year but it is not yet widely available). Moreover, Dukoral is available without a prescription in Canada (and also I believe in New Zealand). It’s a big seller in Canada and widely used by Canadians abroad.

It has long been my position that if a medical drug or device has been approved in another developed country then it ought to be approved in the United States. If it’s good enough for the Canadians then it’s good enough for me.

Never let it be said that I don’t follow through on my beliefs. I arranged for someone to buy me some Canadian Dukoral and ship it over the border. Unfortunately, my “connect” is not as practiced in the art of evading U.S. customs as would be ideal and in a fit of regrettable honesty wrote “gift, diarrhea medicine” on the package. The ever-vigilant U.S. Customs intercepted and confiscated my package, thus saving me from the dangers of FDA-unapproved medicine. So I am out $150 (2 doses) and will be less than fully protected on my trip.

If my son or I become “indisposed” in India, I will know who to blame.

That is the topic of my latest Bloomberg column, here is the last bit:

I don’t mean to say that technological stagnation is a good thing. But sometimes the biggest advances lead to more tragedy than comfort, especially in the short run, before we learn how to adjust to their challenges. To paraphrase Peter Thiel, they promised us flying cars, and what we got was a bunch of stoned characters, and more than 140 of them. Beware the end of the productivity slowdown.

Do read the whole thing.

How to make annoying alarms

by on December 23, 2016 at 1:07 am in Law, Medicine, Science | Permalink

The faster an alarm goes, the more urgent it tends to sound. And in terms of pitch, alarms start high. Most adults can hear sounds between 20 Hz and 20,000 Hz—Baldwin uses 1,000 Hz as a base frequency, which is at the bottom of the range of human speech. Above 20,000 Hz, she says, an alarm “starts sounding not really urgent, but like a squeak.”

Harmonics are also important. To be perceived as urgent, an alarm needs to have two or more notes rather than being a pure tone, “otherwise it can sound almost angelic and soothing,” says Baldwin. “It needs to be more complex and kind of harsh.” An example of this harshness is the alarm sound that plays on TVs across the U.S. as part of the Emergency Alert System. The discordant noise is synonymous with impending doom.

After the alarm designers create a range of sounds in the lab, says Baldwin, they will test the annoyance factor of these sounds in a process called “psychophysical matching, or psychophysical ratings.” Yes, this involves subjecting human beings to a bunch of irritating sounds. Participants determine how annoying the sounds are by sorting them into categories ranking them on a scale of one to 100. 

Then there’s more testing. “If it’s a medical alarm, for instance, we’ll start using that sound and then we’ll maybe measure people’s physiological response to it—does their heart rate go up, does their skin conductance level go down, what happens to their brain activity,” says Baldwin. Skin conductance measures how much the sound affects the body—skin gets better at conducting electricity when the body is physiologically aroused.

An effective audio alarm is one in which the annoyance factor and perceived urgency of the sound is matched to the hazard level—a soft little chime for the fridge door, say, and a “BREHHHHK BREHHHHK BREHHHHK” for a plane in a tailspin. “We want it to be detectable, so to get your attention, but for you to recognize what it means right away,” says Baldwin.

It turns out this is a problem in hospitals:

In hospitals in particular, there are “so many nuisance alarms going off all the time, that people—nurses, doctors—just tune them out,” says Baldwin. “They don’t even hear them anymore.” The statistics say that most of these alarms are not indications of peril. A 2012 review of medical audio alarms found that in one intensive therapy unit, “of 1455 soundings of alarms, only eight were associated with potentially life-threatening problems.”

Here is the full piece, from the excellent Atlas Obscura, and for the pointer I thank Torsten Kehler.

I was pleased to see their title for the column: “Go Wet, Young Man.”  Here is one of the claims:

Counterintuitively, I see the greatest promise for seasteading as a path toward more rather than less human companionship.

…some of the elderly have started living on cruise ships full-time. A good assisted-living facility might cost $80,000 a year in the U.S., more than many year-long cruises. (Cruising could also be cheaper than living in an expensive neighborhood.) Furthermore, the cruise offers regular contact with other passengers and also the crew, and the lower average age means that fewer of one’s friends and acquaintances are passing away. The weather may be better, and there is the option of going onshore to visit relatives and go shopping.

The cruise ship removes the elderly from full-service hospitals, but on the plus side, regular social contact is good for health, passengers are watched much of the time and there is a doctor minutes away. Better health and human companionship could be major motives for this form of seasteading. I could imagine many more of the elderly going this route in the future, and some cruise lines already are offering regular residences on board.

The goal of this seasteading enterprise is to pack people more tightly together rather than to open up broad new vistas for a Wild West kind of settlement. The proprietors make physical space more scarce, not less, to induce better clustering. So seasteading does have a future, but it is to join and build a new and crowded communitarian project, not to get away from one.

Do read the whole thing.