Category: Medicine

Guinea pig questions

by  Tyler Cowen in

If someone demographically normal and not especially at-risk wants to serve as a guinea pig, what is the optimal allocation of that resource?

Is there any formal discussion of this question? I know they say “there is always an Effective Altruism blog post,” but is there?

Mostly I have medicine and medical experimentation in mind, but I can imagine other answers as well, such as “trying to leap forty flaming cars with a motorcycle.”  Though I doubt that one will end up as the winner.  In any case, I am assuming away legal constraints.  Where can you volunteer as a guinea pig for the highest social value?

The Adderall Shortage: DEA versus FDA in a Regulatory War

by  Alex Tabarrok in

A record number of drugs are in shortage across the United States. In any particular case, it’s difficult to trace out the exact causes of the shortage but health care is the US’s most highly regulated, socialist industry and shortages are endemic under socialism so the pattern fits. The shortage of Adderall and other ADHD medications is a case in point. Adderall is a Schedule II controlled substance which means that in addition to the FDA and other health agencies the production of Adderall is also regulated, monitored and controlled by the U.S. Drug Enforcement Administration (DEA).

The DEA aims to “combat criminal drug networks that bring harm, violence, overdoses, and poisonings to the United States.” Its homepage displays stories of record drug seizures, pictures of “most wanted” criminal fugitives, and heroic armed agents conducting drug raids. With this culture, do you think the DEA is the right agency to ensure that Americans are also well supplied with legally prescribed amphetamines?

Indeed, there is a large factory in the United States capable of producing 600 million doses of Adderall annually that has been shut down by the DEA for over a year because of trivial paperwork violations. The New York Magazine article on the DEA created shortage has to be read to be believed.

Inside Ascent’s 320,000-square-foot factory in Central Islip, a labyrinth of sterile white hallways connects 105 manufacturing rooms, some of them containing large, intricate machines capable of producing 400,000 tablets per hour. In one of these rooms, Ascent’s founder and CEO — Sudhakar Vidiyala, Meghana’s father — points to a hulking unit that he says is worth $1.5 million. It’s used to produce time-release Concerta tablets with three colored layers, each dispensing the drug’s active ingredient at a different point in the tablet’s journey through the body. “About 25 percent of the generic market would pass through this machine,” he says. “But we didn’t make a single pill in 2023.”

… the company has acknowledged that it committed infractions. For example, orders struck from 222s must be crossed out with a line and the word cancel written next to them. Investigators found two instances in which Ascent employees had drawn the line but failed to write the word.

The causes of the DEA’s crackdown appears to be precisely the contradiction in its dueling missions. Ascent also produces opioids and the DEA crackdown was part of what it calls Operation Bottleneck, a series of raids on a variety of companies to demand that they account for every pill produced.

To be sure, the opioid epidemic is a problem but the big, multi-national plants are not responsible for fentanyl on the streets and even in the early years the opioid epidemic was a prescription problem (with some theft from pharmacies) not a factory theft problem (see figure at left). Maybe you think Adderall is overprescribed. Could be but the DEA is supposed to be enforcing laws not making drug policy. The one thing one can say for certain is that Operation Bottleneck has surely been a success in creating shortages of Adderall.

The DEA’s contradictory role in both combating the illegal drug trade and regulating the supply of legal, prescription drugs is highlighted by the fact that at the same as the DEA was raiding and shutting down Ascent, the FDA was pleading with them to increase production!

For Ascent, one of the more frustrating parts of being told by the government to stop making Adderall is that other parts of the government have pleaded with the company to make more. The company says that on multiple occasions, officials from the FDA asked it to increase production in response to the shortage, and that Ron Wyden, the Democratic senator from Oregon, also pressed Ascent for help. They received responses similar to those the company gave the stressed-out callers looking for pills: Ascent didn’t have any information. Instead, the company directed them to the DEA.

UNOS Kills

by  Alex Tabarrok in

I’ve long been an advocate of increasing the use of incentives in organ procurement for transplant; either with financial incentives or with rules such as no-give, no-take which prioritize former potential organ donors on the organ recipient list. What I and many reformers failed to realize, however, is that the current monopolized system is so corrupt, poorly run and wasteful that thousands of lives could be saved even without incentive reform. (To be clear, these issues are related since an incentivized system would never have become so monopolized and corrupt in the first place but that is a meta-issue for another day.) Here, for example, is one incredible fact:

 An astounding one out of every four kidneys that’s recovered from a generous American organ donor is thrown in the trash.

Here’s another:

Organs are literally lost and damaged in transit every single week. The OPTN contractor is 15 times more likely to lose or damage an organ in transit than an airline is a suitcase.

Organs are not GPS-tracked!

In an era when consumers can precisely monitor a FedEx package or a DoorDash dinner delivery, there are no requirements to track shipments of organs in real time — or to assess how many may be damaged or lost in transit.

“If Amazon can figure out when your paper towels and your dog food is going to arrive within 20 to 30 minutes, it certainly should be reasonable that we ought to track lifesaving organs, which are in chronic shortage,” Axelrod said.

Here’s one more astounding statistics:

Seventeen percent of kidneys are offered to at least one deceased person before they are transplanted….

Did you get that? The tracking system for patients is so dysfunctional that 17% of kidneys are offered to patients who are already dead–thus creating delays and missed opportunities.

All of this was especially brought to light by Organize, a non-profit patient advocacy group who under an innovative program embedded with the HHS and working with HHS staff produced hard data.

Many more details are provided in this excellent interview with Greg Segal and Jennifer Erickson, two of the involved principals, in the IFPs vital Substack Statecraft. 

In Conversation with Próspera CEO Erick Brimen & Vitalia Co-Founder Niklas Anzinger

by  Alex Tabarrok in

During my visit to Prospera, one of Honduras’ private governments under the ZEDE law, I interviewed Prospera CEO Erick Brimen and Vitalia co-founder Niklas Anzinger. I learned a lot in the interview including the real history of the ZEDE movement (e.g. it didn’t begin with Paul Romer). I also had not fully appreciated the power of reciprocity stacking.

Companies in Prospera have the unique option to select their regulatory framework from any OECD country, among others. Erick Brimen elaborated in the podcast how this enables companies to do normal, OECD approved, things in Prospera which literally could not be done legally anywhere else in the world.

…so in the medical world for instance you have drugs that are approved in some countries but not others and you have medical practitioners that are licensed in some countries but not the others and you have medical devices approved in some countries but not others and there’s like a mismatch of things that are approved in OECD countries but there’s no one location where you can say hey if they’re approved in any country they’re approved here. That is what Prosper is….Our hypothesis is that just by doing that we can leapfrog to a certain extent and it’s got nothing to do with the wild west or doing weird things.

…so here so you can have a drug approved in the UK but not in the US with a doctor licensed in the US but not in the UK with a medical device created in Israel but not yet approved by the FDA following a procedure that has been say innovated in Canada, all of that coming together here in Prospera.

As it should be

by  Tyler Cowen in

The next time you send your doctor an email, don’t be surprised if they charge you a fee to answer.

More healthcare groups are charging fees to answer patients’ electronic messages, often the ones you exchange via their portal. Doctors say it’s only fair if they’re spending time on the messages and note that an email discussion can often save you the time of having to come in.

The typical cost of an email message claim was $39 in 2021, including both the portion paid by insurance and by the patient, according to a Peterson-KFF Health System Tracker analysis.

Some patients have been taken aback by the charges. They are surprised at the notifications on portals about the change, and irritated at the idea of a new fee.

Dr. Lauren Oshman, a family physician and associate professor at the University of Michigan Medical School, says she initially experienced some patient resistance and anger about the prospect of being billed for emails.

Now, she says, patients are typically pleased that they are able to get a direct response from her through a portal message.

“They’re thrilled when they get me directly,” she says.

Here is more from the WSJ, via the excellent Daniel Lippman.

What can be learned from Singaporean health care institutions?

by  Tyler Cowen in

Besides the usual, that is.  Max Thilo of the UK has a new and excellent study on this, here is one excerpt from the foreword by Lord Warner:

Second, and critical, the Singaporeans are not fixated on delivering services from acute hospitals – the most expensive part of any healthcare system because of its fixed overheads and expensive maintenance. As this report demonstrates “the reason why Singapore spends so much less on health than other developed countries is its low hospital utilisation.” Instead, Singapore has invested in highly productive polyclinics and low-cost telemedicine. The result is that Singaporeans can visit their GP more often than English patients. In their polyclinics they also improve productivity by separating chronic and acute care.

And from Max:

During a recent trip, I met with the CEO of the largest telemedicine provider in Singapore. He casually mentioned that UK patients were already using his service. This seemed surprising. No comprehensive data is available for the costs of UK telemedicine services, so I googled the cost of online appointments in the UK and Singapore. Singaporean appointments are less than half the price of those in the UK. The most affordable online appointment I found in the UK was £29. Yet, many providers charge significantly more – for instance, Babylon Health lists its price for private GP appointments at £59. In contrast, Doctor Anywhere, Singapore’s leading telemedicine provider, offers services for just £12.27 Doctor Anywhere has an app where patients can log on and see patients virtually. They make and then register the diagnosis. The rest of the process, including referrals and prescriptions, is automated.

Recommended.

U.S.A. yikes fact of the day

by  Tyler Cowen in

Between January 2016 and December 2022, the monthly antidepressant dispensing rate increased 66.3%, from 2575.9 to 4284.8. Before March 2020, this rate increased by 17.0 per month (95% confidence interval: 15.2 to 18.8). The COVID-19 outbreak was not associated with a level change but was associated with a slope increase of 10.8 per month (95% confidence interval: 4.9 to 16.7). The monthly antidepressant dispensing rate increased 63.5% faster from March 2020 onwards compared with beforehand. In subgroup analyses, this rate increased 129.6% and 56.5% faster from March 2020 onwards compared with beforehand among females aged 12 to 17 years and 18 to 25 years, respectively. In contrast, the outbreak was associated with a level decrease among males aged 12 to 17 years and was not associated with a level or slope change among males aged 18 to 25 years.

That is by Kao-Ping Chua, et.al., from the high-quality journal Pediatrics.  So that is how we respond to crises?  By doping up the young women?  Yikes!

Via the excellent Kevin Lewis.

Genetic Insurance

by  Alex Tabarrok in

Genetic testing identifies disease risk, enabling individuals to dodge environmental triggers, optimize treatments, and improve planning. Yet, the fear of increased insurance premiums deters many from undergoing tests. Genetic testing offers societal benefits but also presents significant distributional challenges. To address this, my 1994 paper proposed the idea of genetic insurance.

For a small fee genetic insurance would insure against the possibility of a positive test result. If the test came back positive the customer would be paid a large sum of money, enough to cover the expected costs of his disease or equivalently enough to allow him to purchase health insurance at the new risk premium. If the test turns out negative the customer would lose his genetic insurance fee but would gain the results of the test and also lower health insurance premiums. Those who have positive tests results would be paid enough money to pay their health care costs and would also benefit from being able to plan in accord with the test results. Under this proposal average insurance rates will fall and everyone will be made better off.\

Genetic insurance is insurance against changes in the cost of health insurance due to genetic information. John Cochrane would later generalize this idea to show that it’s possible to insure against changes in the cost of health insurance due to any new information. Cochrane called this time-consistent health insurance or health-status insurance; it’s a way of creating long-term health insurance contracts without binding an individual to a firm.

In an interesting paper, Helene Schernberg extends my 1994 paper. Schernberg shows that even if an individual has full-health insurance that can’t be taken away, there are other reasons to want genetic insurance. She focuses on the planning aspect. Genetic insurance could be used to shift consumption earlier, to better health states and thus improve life-time allocation.

Genetic testing could soon be a routine part of your medical journey. It offers insights into inherited disorders or susceptibility to various conditions. For example, if you are a woman with a BRCA mutation, you have a 55 to 72% lifetime risk of breast cancer.

… This suggests that genetic information is valuable while providing a theoretical argument in favor of genetic insurance. The mechanism is described in Tabarrok (1994): Individuals purchase genetic insurance before taking a genetic test, thus receiving a compensation upon being identified as a high-risk. Tabarrok (1994) relates this genetic insurance payment to the need to cover expensive health insurance premia. I show that it also relates to the fact that a temporally risk-averse individual wishes to insure against the lifetime utility losses she may experience when her health prospects deteriorate after taking a genetic test.

Monopolized organ collection

by  Tyler Cowen in

The nation’s 56 organ procurement organizations collect organs — mainly kidneys — from deceased donors at hospitals and arrange for them to be transported to surgeons at the 250 U.S. medical centers that perform transplants. Each procurement group holds a government-guaranteed monopoly over a swath of U.S. territory where it operates.

Some have failed for years to collect enough organs to meet demand, according to government records. But the Centers for Medicare and Medicaid Services, the part of HHS that licenses the nonprofits to operate, has never decertified one. In response to critiques, the CMS issued new benchmarks that will allow the agency to weed out poor performers beginning in 2026.

Now many of these organ collection groups are under investigation for fraud and overbilling the government.

Access to Medical Data Saves Lives

by  Alex Tabarrok in

ProPublica: In January, the Biden administration pledged to increase public access to a wide array of Medicare information to improve health care for America’s most sick and vulnerable.

…So researchers across the country were flummoxed this week when the Centers for Medicare and Medicaid Services announced a proposal that will increase fees and diminish access to claims data that has informed thousands of health care studies and influenced major public health reforms.

Using big Medicare databases has never been cheap or easy. Under the current system, researchers could have the data transferred to secure university computers for about $20,000–that’s a lot but once the data was on the university computers it could be accessed by multiple researchers, cutting costs. A professor could buy the data and their PhD students, for example, wouldn’t have to pay again. Under the new system it will cost $35,000 for one researcher to access the data which will be held on government (CMS) computers. Moreover, it’s unclear how complex statistical analysis will be performed or how congested the CMS systems may become.

Research teams on complex projects can include dozens of people and take years to complete. “The costs will grow exponentially and make access infeasible except for the very best resourced organizations,” said Joshua Gottlieb, a professor at the University of Chicago’s Harris School of Public Policy.

Public data should be open access to researchers, with appropriate anonymization. We know from IP law that barriers to access reduce research and innovation; and in the medical sphere research and innovation saves lives. Open access is also a check on how governments spends taxpayer money and the effectiveness of such spending. I also worry that raising the dollar cost of access is a prelude to other restrictions. The NIH, for example, is restricting access to genetic data if it thinks the researcher will be asking forbidden questions. Even without such explicit restrictions, there is a chilling effect when researchers are beholden for access to the government and indeed to the very agencies they may be researching.

I place a high value on privacy but I get suspicious when governments invoke privacy to block citizen access to government data but not to block government access to citizen data. Medicare databases have always been appropriately anonymized and care is taken so the data are secured but the dangers of these databases in anyone’s hand, let alone researchers, is far less than anti-money laundering, KYC laws and suspicious transaction reports in banking, automated license plate readers that the police us to scan billions of license plates or mass surveillance of the communications of US citizens under FISA. Sadly, this list could easily be extended. Liberty thrives on the people’s privacy and the government’s transparency.

Give Innovation a Chance

by  Alex Tabarrok in

Elizabeth Currid-Halkett writing in the NYTimes discusses her son’s muscular dystrophy and his treatment with the controversial gene-therapy Elevidys. Currid-Halkett, like many parents whose children have been treated with Elevidys, reports much better results than appear in the statistics.

On Aug. 29, [my son] finally received the one-time infusion. Three weeks later, he was marching upstairs and able to jump over and over. After four weeks, he could hop on one foot. Six weeks after treatment, Eliot’s neurologist decided to re-administer the North Star Ambulatory Assessment, used to test boys with D.M.D. on skills like balance, jumping and getting up off the floor unassisted. In June, Eliot’s score was a 22 out of 34. In the second week of October, it was a perfect 34 — that of a typically developing, healthy 4-year-old boy. Head in my hands, I wept with joy. This was science at its very best, close to a miracle.

…a narrow focus on numbers ignores the real quality-of-life benefits doctors, patients and their families see from these treatments. During the advisory committee meeting for Elevidys in May 2023, I listened to F.D.A. analysts express skepticism about the drug after they watched videos of boys treated with Elevidys swimming and riding bikes. These experts — given the highest responsibility to evaluate treatments on behalf of others’ lives — seemed unable to see the forest for the trees as they focused on statistics versus real-life examples.

Frankly, I side with the statistics. We don’t hear from the parents in the placebo group whose children also spontaneously made improvements.

Even though I side the statistics, I side with approval. Innovation is a dynamic process. It’s not surprising that the first gene therapy for DMD offers only modest benefits; you don’t hit a home run the first time at bat. But if the therapy isn’t approved, the scientists don’t go back to the drawing board and keep going. If the therapy isn’t approved, it dies and you lose the money, experience and learning by doing that are needed to develop, refine and improve.

Approval is not the end of innovation but a stepping stone on the path of progress. Here’s an example I gave earlier of the same principle. When we banned supersonic aircraft, we lost the money, experience and learning by doing needed to develop quieter supersonic aircraft. A ban makes technological developments in the industry much slower and dependent upon exogeneous progress in other industries.

You must build to build better.

Addendum: Peter Marks is the best and perhaps the most important director CBER has ever had. CBER, the Center for Biologics Evaluation and Research, is responsible for biological products, including vaccines and gene therapies. Marks has repeatedly pushed and sometimes overruled his staff in approving products like Elevidys. Marks named and was the driving force at the FDA behind Operation Warp Speed, a tremendous FDA success and break with tradition. Marks has been challenging the FDA’s conservative culture. I hope his changes survive his tenure.

Avoiding Repugnance

by  Alex Tabarrok in

Works in Progress has a good review of the state of compensating organ donors, especially doing so with nudges or non-price factors to avoid backlash from those who find mixing money and organs to be repugnant. My own idea for this, first expressed in Entrepreneurial Economics, but many times since is a no-give, no-take rule. Under no-give, no-take, people who sign their organ donor cards get priority should they one day need an organ. The great virtue of no-give, no-take is that it provides an incentive to sign one’s organ donor card but one that strikes most people as fair and just and not repugnant. Israel introduced a no-give, no-take policy in 2008 and it appears to have worked well.

In March 2008, to increase donations, the Israeli government imple­mented a ‘priority allocation’ policy to encourage more people to sign up to donate organs after their deaths. Once someone has been registered as a donor for three years, they receive priority allocation if they themselves need a transplant. If a donor dies and their organs are usable, their close family members also get higher priority for transplants if they need them – ​which also means that families are more inclined to give their consent for their deceased relatives’ organs to be used.

In its first year, the scheme led to 70,000 additional sign-ups. The momentum continued, with 11.1 percent of all potential organ donors being registered in the five years after the scheme was introduced, compared to 7.7 percent before. According to a 2017 study, when presented with the decision to authorize the donation of their dead relative’s organs, 55 percent of families decided to donate after the priority scheme, compared to 45 percent before.