Category: Medicine
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.
Will Trump Appoint a Great FDA Commissioner?
A German newspaper asked for my take on the nomination of RFK Jr. to head HHS. Here’s what I said:
Operation Warp Speed stands as the crowning achievement of the first Trump administration, exemplifying the impact of a bold public-private partnership. OWS accelerated vaccine development, production, and distribution beyond what most experts thought possible, saving hundreds of thousands of American lives and demonstrating the power of American ingenuity in a time of crisis.
By nominating Robert F. Kennedy Jr., a prominent anti-vaccine activist, President Trump undermines his own legacy, and casts doubt on his administration’s commitment to protecting American lives through science-driven health policy.
Many better choices are available. Here is my 2017 post on potential people to head the FDA, many of which would also be great at HHS. No indent. Key points remain true.
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.
China’s Libertarian Medical City
You’ve likely heard of Prospera, the private city in Honduras established under the ZEDE (Zone for Employment and Economic Development) law, which has drawn global investment for medical innovation. The current Honduran government is trying to break its contracts and evict Prospera from 
Honduras. The libertarian concept of an autonomous medical hub, free to attract top talent, pharmaceuticals, medical devices, ideas, and technology from around the world is, however, gaining traction elsewhere—most notably and perhaps surprisngly in the Boao Hope Lecheng Medical Tourism Pilot Zone in Hainan, China.
Boao Hope City is a special medical zone supported by the local and national governments. Treatments in Boao Hope City do not have to be approved by the Chinese medical authorities as Boao Hope City is following the peer approval model I have long argued for:
Daxue: Medical institutions within the zone can import and use pharmaceuticals and medical devices already available in other countries as clinically urgent items before obtaining approval in China. This allows domestic patients to access innovative treatments without the need to travel abroad…. The medical products to be used in the pilot zone must possess a CE mark, an FDA license, or PMDA approval, which respectively indicate that they have been approved in the European Union, the US, and Japan for their safe and effective use.
Moreover, evidence on the new drugs and devices used within the zone can be used to support approval from the Chinese FDA–this seems to work similar to Bartley Madden’s dual track procedure.
Daxue: Since 2020, the National Medical Products Administration has introduced regulations on real-world evidence (RWE), with the pilot zone being the exclusive RWE pilot in China. This means that clinical data from licensed items used within the zone can be transformed into RWE for registration and approval in China. Consequently, medical institutions in the zone possess added leverage in negotiations with international pharmaceutical and medical device manufacturers seeking to enter the Chinese market.
… This process significantly reduces the time required for approval to just a few months, saving businesses three to five years compared to traditional registration methods. As of March 2024, 30 medical devices and drugs have been through this process, among which 13 have obtained approval for being sold in China.
The zone also uses peer-approval for imports of health food, has eliminated tariffs on imported drugs and devices and waived visa requirements for many medical tourists.
To be sure, it’s difficult to find information about Boao Hope medical zone beyond some news reports and press releases so take everything with a grain of salt. Nevertheless, the free city model is catching on. There are already 29 hospitals in the zone including international hospitals and hundreds of thousands of medical tourists a year. The medical zone is part of a larger free port project.
Prospera is ideally placed for a medical zone for North and South America. The Honduran government should look to China’s Boao Hope Medical Zone to see what Prospera could achieve for Honduras with support instead of oppositon.
Hat tip: MvH.
Do you want a Democratic or Republican doctor?
Political polarization is increasingly affecting policymaking, but how is it influencing professional decision-making? This paper studies the differences in medical practice between Republican and Democratic physicians over 1999-2019. It links physicians in the Medicare claims data with their campaign contributions to determine their partyalignment. In 1999, there were no partisan differences in medical expenditure perpatient. By 2019, Republican physicians are now spending 13% more, or $70 annually per patient. We analyze four potential sources of this partisan difference: practice characteristics (i.e., specialization and location), patient composition, preferences for financial gain, and beliefs about appropriate care. Even among physicians in the same specialty and location treating patients for the same condition, Republican physicians spend 6% more, especially on elective procedures. Using a movers design, we also find large partisan differences for treating the same patient. We find no evidence that these partisan differences are driven by profit incentives. Instead, the evidence points to diverging beliefs. Republican physicians adhere less to clinical guidelines, consistent with their reported beliefs in prior surveys. The timing of the divergence matches the politicization of evidence-based medicine in Congress. These results suggest that political polarization may lead to partisan differences in the beliefs and behavior of practitioners.
That is from the job market paper of Woojin Kim from UC Berkeley. I found this one of the most interesting job market papers of this year.
How Low Socioeconomic Status Hinders Organ Donation
Past studies find that lower socioeconomic status (SES) individuals are less likely to donate organs. Building on the extended self literature, we propose that this effect occurs in part because the body is more central to the sense of self of lower-SES individuals. We test our predictions across seven studies (N = 8,782) conducted in different countries (United States and Brazil) with qualitative, observational, and experimental data in controlled and field settings. Results show that lower-SES individuals ascribe a greater weight to their bodies in forming their self-concept, which reduces their willingness to donate organs.
That is from a new paper by Yan Vietes and Chiraag Mittal. Via the excellent Kevin Lewis.
The Health and Employment Effects of Employer Vaccination Mandates
Health care facilities considering mandating staff vaccination face a difficult tradeoff. While additional vaccination coverage will directly reduce disease transmission within the facility, the imposition of a mandate may also cause vaccine-hesitant staff to quit, which could harm patient care. To study this tradeoff, we leverage comprehensive administrative data covering virtually all US nursing homes, including payroll-based records on approximately 500 million daily nurse shifts and weekly data on COVID transmission and mortality at each facility. We use a difference-in-differences framework to estimate the impact of employer-imposed vaccine mandates at 581 nursing homes on disease spread, employment outcomes, and several patient care metrics. While mandates did slightly increase staff turnover, the effects were concentrated on staff working less than 20 hours per week, and resulted in a reduction of less than two minutes per patient-day. Furthermore, there is only limited evidence of lower levels of care at mandate facilities in typically-monitored conditions such as patient falls, pressure ulcers, or urinary tract infections. In contrast, implementing a vaccine mandate led to large increases in staff vaccinations at mandate facilities, which directly led to less transmission of and lower patient mortality from COVID. We estimate that vaccine mandates saved one patient life for every two facilities that enacted a mandate, a large effect given the typical facility has around 100 beds. Our results suggest that the health benefits of mandates far outweigh the costs in terms of reduced patient care from staff turnover.
Yup. For some of you, it is time to read it and weep. Here is the full paper by
Ethiopia fact of the day
More than 6.1 million malaria cases, and 1,038 deaths, have been recorded in the country this year through the end of September, compared with 4.5 million cases, and 469 deaths, for all of 2023. Worse, cases are likely to soar far higher in the next couple of months because peak malaria season, driven by seasonal rains, begins in September and runs through the end of the year.
“We’re backsliding so fast — we’ve gone back a decade,” said Fitsum Tadesse, the lead scientist overseeing the malaria program at the Armauer Hansen Research Institute in Addis Ababa, the capital of the country.
Here is more from the NYT.
Quantifying the Super-Villains
There is a new paper on this topic:
We investigate the effects of substantial Medicare price reductions in the medicaldevice industry, which amounted to a 61% decrease over 10 years for certain devicetypes. Analyzing over 20 years of administrative and proprietary data, we find theseprice cuts led to a 25% decline in new product introductions and a 75% decrease inpatent filings, indicating significant reductions in innovation activity. Manufacturersdecreased market entry and increased outsourcing to foreign producers, associatedwith higher rates of product defects. Our calculations suggest the value of lost inno-vation may fully offset the direct cost savings from the price cuts. We propose thatbetter-targeted pricing reforms could mitigate these negative effects. These findingsunderscore the need to balance cost containment with incentives for innovation andquality in policy design.
By Yunan Ji and Parker Rogers. Here is a summary tweet storm. Via Sam Hammond.
Iranian Kidney Donors
Iran is one of the few countries in the world to have eliminated the shortage of kidneys. A useful new paper looks at what donors are like,
First some background:
The adoption of a regulated market mechanism for kidney procurement in Iran started in 1988 in the absence of sufficient posthumous donations (Ghods and Savaj, 2006). The mechanism allows living unrelated Iranian individuals to donate kidneys to Iranian patients with end stage renal disease (ESRD) for financial gains. The program was successful in eliminating the renal transplant waiting list within a decade of its implementation (Mahdavi-Mazdeh, 2012). In addition, the Organ Transplant Act legalized brain-stem death donations in 2000. Both ESRD patients and potential kidney donors are referred to and registered with The Association for Supporting Renal Patients, a non-profit organization (NGO) which conducts a primary medical evaluation and facilitates the market exchange. Upon successful completion of the test, a formal consent is acquired and the potential donor and the recipient are introduced to each other. At this stage both the patient and the donor are referred to a nephrologist for further evaluation, cross-match, and angiography. If the patient-donor pair is compatible, in the next step the pair negotiate the terms and conditions of the exchange. All terms within the price-cap are guaranteed and enforceable by the NGO. The price-cap is frequently adjusted for inflation and during the course of our study was set at 180 million Iranian Rial (US$4700 in August 2017). However, the negotiation is private and the pair can agree any terms they wish. The donor also receives a “gift of altruism” and 1 year of insurance from the government through the Charity Foundation for Special Diseases. Transplant surgery is carried out free of charge in public university hospitals. The Iranian Ministry of Health and Medical Education introduced further procedural changes in July 2019. In particular, they established a center for organ transplant and procurement at the ministry which acts as the matching centre and provides oversight and overall control of the process.
Are the donors irrational, risk-loving, impatient? No, they are normal people making the best of sometimes limited opportunities:
The overall picture is of individuals who were in financial need, often unemployed but with a family to support and where alternatives sources of financial support were grim. However, despite their financial position, these individuals were typically patient and not especially prone to risk-taking. They were no less rational than the average, but those who ended up completing the process might be characterized as more altruistic than those who did not….More broadly our findings indicate that even in situations of extreme poverty we should not assume lower levels of rationality will be pervasive.
Given that donation saves lives and that kidney donation is not especially risky (much less risky than driving a motorcycle, for example) the tradeoff seems positive and well within ordinary bounds.
Turning to the US, here is Sally Satel on a proposed tax credit for kidney donation:
What if we could solve the organ donor shortage with a simple tax credit? That is the idea behind the End Kidney Deaths Act (EKDA) (HR 9275).
The bill, advanced by the Coalition to Modify NOTA (NOTA stands for the National Organ Transplant Act passed in 1984) would provide a $50,000 refundable tax credit—$10,000 per year for five years—to any living donor who gave a kidney to the next person on the waiting list. The tax credit would be a 10-year pilot program.
The credit would save 10,000 to perhaps as many as 100,000 lives over ten years.
FYI, I am a supporter of Modify NOTA (along with Al Roth, Steve Levitt, and Mario Macis, to name just a few of the economists, joined by surgeons, nephrologists and others).
Hat tip: Kevin Lewis.
Fluoride revisionism?
I am usually skeptical of such efforts, but Journal of Health Economics is quite a serious outlet:
Community water fluoridation has been named one of the 10 greatest public health achievements of the 20th century for its role in improving dental health. Fluoride has large negative effects at high doses, clear benefits at low levels, and an unclear optimal dosage level. I leverage county-level variation in the timing of fluoride adoption, combined with restricted U.S. Census data that link over 29 million individuals to their county of birth, to estimate the causal effects of childhood fluoride exposure. Children exposed to community water fluoridation from age zero to five are worse off as adults on indices of economic self-sufficiency (−1.9% of a SD) and physical ability and health (−1.2% of a SD). They are also significantly less likely to graduate high school (−1.5 percentage points) or serve in the military (−1.0 percentage points). These findings challenge existing conclusions about safe levels of fluoride exposure.
That new article is by Adam Roberts. Via the excellent Kevin Lewis.
Northern Ireland fact of the day
The NHS in Northern Ireland is the worst in the UK. During the quarter April/June 2021, over 349,000 people were waiting for a first appointment, 53 percent for over a year, an increase of 39,000 for the same period in 2020. Adjusted for population size, waiting lists in Northern Ireland are 100 times greater than those in England, a country 50 times its size.
That is from the truly excellent Perils and Prospects of a United Ireland, by Padraig O’Malley. Imagine a detailed, thoughtful 500 pp. book on political issues you probably don’t care all that much about — is there any better way to study politics and political reasoning? Every page of this book offers substance.
Elsewhere, of course, we are told that reluctance to give up their health care system is a major reason why Irish reunification is not more popular in the North, and that holds for Catholics too.
This one will make the best non-fiction of the year list.
Incentives matter, the demand curve slopes downward, mental health edition
Since 2000, pharmaceuticals for common psychiatric conditions aged out of patent protection. After generic entry, supply increases as more sellers enter the market, leading to lower prices – about 80-85% less! Cheaper prescriptions and more treatment are the stated goal of policies to improve affordability.
…Drug prices definitely fell during this period. For the SSRI sertraline, consumer cost per month dropped from ~35 dollars in the mid-2000s to ~6 dollars by the mid 2010s. Total Medicaid spending on antidepressants peaked in 2004 ($2 billion) then declined through 2018 ($750 million). Authors of that paper note that “generic drug prices steadily decreased over time” while utilization increased. From 2013 to 2018, both out-of-pocket costs and total expenditures per prescription fill went down for antidepressants and antipsychotics. For antipsychotics, generic drug claims grew 35% from 2016 to 2021.
According to the DEA, total dispensing of stimulants jumped 58% from 2012 to 2022; note how this follows the generic entry of long-acting Ritalin (methylphenidate) and Adderall (amphetamine) products. More recently, stimulant prices shot up amid shortages.
And:
By the mid 2010s, people with psychiatric conditions were better able to afford mental health care. Young adults, now on their parents insurance, saw declining out of pocket costs for behavioral health in particular. For people aged 18-25, “mental health treatment increased by 5.3 percentage points relative to a comparison group of similar people ages 26–35.” Even for employer plans, in-network prices and cost-sharing decreased from 2007 to 2017…
Here is the full essay by AffectiveMedicine. It has numerous other points of interest.