Category: Regulations

Regulations Slow the Creation and Adoption of Healthcare Breakthroughs

CPR is “cardiopulmonary resuscitation.” ECPR is “extracorporeal CPR.” The ATTEST randomized double-blind clinical trial (RCT) provided dramatic evidence of the efficacy of ECPR. But the INCEPTION RCT seemed to provide equally strong evidence of a lack of efficacy. The key difference is the high level of experience and dedication of those implementing the ATTEST RCT, and the lack of experience, and likely lower dedication of those in the INCEPTION RCT. Dr. Demetris Yannopoulos has improved his techniques through trial and error, probably in some ways that he can articulate and in other ways that are harder to articulate. Gary Klein with his naturalistic decision-making research, writes that experience gives emergency workers a quick “recognition” of what needs to be done in different situations.

At what point in the development of a therapy do you perform the canonical RCT? In the case of Emil Freireich’s four drug chemo-cocktail for curing childhood leukemia, he continually improved the ingredients and doses of the cocktail. If an RCT had been performed too early in that process, the result would have been a lack of efficacy, and a therapy would have been abandoned that had the potential to be developed into a useful efficacious therapy. Ditto for Vince DeVita’s development of his chemo-cocktail for curing Hodgkin’s Lymphoma. Ditto also for the development of the drug that eventually proved efficacious in the For Blood and Money book, where Stanford cancer doctor and Pharmacyclics co-founder acquired and developed cancer therapy Imbruvica, but abandoned it after an RCT of it failed. But Miller was ousted by major Pharmacyclics stock-holder, and entrepreneurial non-scientist, Bob Duggan, who did not want to give up on Imbruvica. Duggan persevered, overseeing its further development, until a later RCT was performed that proved efficacy.

In an earlier entry, I documented a much simpler and cheaper CPR innovation that also promises to improve heart failure therapy, called “neuroprotective CPR” (NCPR). Which one, if either, of ECPR or NCPR should we endorse? Ideally, in a fully function medical marketplace, we could comfortably say: “let the market decide.” Entrepreneurial scientists and physicians could develop the therapies and see how many willing patients would be willing to pay for each. Maybe the more expensive ECPR therapy would initially only be bought by the better-off. But as Yannopoulos improves it, as he is already working to do, making it simpler and cheaper, it would eventually be appealing to a broader customers. In Openness, I claim that this is the common path of a great many breakthrough innovations in areas outside of medicine.

Notice that the ECPR was heavily funded by the Helmsley Trust, a private foundation. This is consistent with my claim that medical innovation benefits from a diversity of funding sources, especially of private funding sources that are more likely to fund a diversity of methods and to take chances with heterodox ideas, partly motivated by private funders’ greater mission-orientation due to having more ‘skin-in-the-game.’

Notice also that Yannopoulos’s implementation of ECPR was constrained by a scarcity of trained personnel. Yannopoulos could not act as a nimble entrepreneur because massive regulations limit nimble entrepreneurship in healthcare. This is especially try on labor market issues where massive labor market regulations pile on top of massive healthcare regulations. Breakthrough innovations are usually implemented by small nimble start-ups. To create Disneyland, Walt Disney created WED Enterprises, instead of try to created it with the large incumbent The Walt Disney Company. Jonathan Bush tried nimble labor market innovation in healthcare, but was stymied by regulations. So in the ECPR case, Yannopoulos had the beds to care for more cardiac arrest patients, but could not fill those rooms because of a lack of trained healthcare workers. He could not simply offer higher pay. He was part of a larger organization where he had limited decision-rights that reduced his nimble control. (On the importance of decision-rights, see Koch 2007.)

(p. 27) In reality, by the time a patient without a pulse arrives in the E.R., we know what the outcome is going to be. We continue CPR and shock the patient if we can. We insert a breathing tube and connect it to a ventilator. We inject medications: adrenaline, heart-rhythm drugs. But these treatments almost always fail.

. . .

Demetris Yannopoulos, an interventional cardiologist and professor at the University of Minnesota Medical School who created its Center for Resuscitation Medicine, refused to accept that this was the best doctors could do. In 2014, he began performing ECPR, a treatment that was starting to catch on in a few places, mostly in Asia and Europe. To his surprise, patients he didn’t expect to survive ended up doing well.  . . .

When a patient in cardiac arrest is placed on an extracorporeal membrane oxygenation (ECMO) machine, as Sauer was, the treatment is called ECPR. The type of ECMO intervention used in ECPR provides full life support, which means it does the work of both lungs and heart. (Another type of ECMO, used on Covid-19 patients, helps just with breathing.) ECMO evolved from the heart-lung machines that started being used during heart surgery in the 1950s.

. . .

ECPR by itself doesn’t actually cure anything. But by providing fresh blood flow to the brain and other organs, it lets the body rest and gives doctors time to fix the underlying problem, if it’s fixable.  . . .  After patients are hooked up to ECMO, angiograms of their hearts are typically performed to determine whether they have clogged arteries — as about 85 percent do. In Sauer’s case, Yannopoulos found a blockage in his largest heart vessel, the left anterior descending artery, also known as “the widow maker.” He inserted a stent to open it back up.

. . .

(p. 28) Several years after the program started, Yannopoulos, Bartos and their team conducted the first randomized, controlled trial of ECPR. The results were published in The Lancet in 2020 as the ARREST trial.  . . .

After enrolling just 30 patients, the ARREST trial was stopped early by an N.I.H. board because the patients who got ECPR did so much better than the control-group subjects who received standard resuscitation, and it would have been unethical to continue the study. After six months, 43 percent of the 14 patients who got ECPR were alive with good brain function, compared with zero in the control group.

. . .

The Helmsley Trust gave Yannopoulos grants totaling $19.4 million, which enabled him to add this “hub and spoke” mobile component to his program: The university hospital would be the hub, and a truck and some local hospitals would be the spokes. “It was a real big bet,” Panzirer told me.

To reach patients in areas that were more suburban and rural, Yannopoulos first had to team up with surrounding health systems. Competition is more often the norm among health systems, rather than collaboration, but he persuaded his chief executive, James Hereford, to gather his counterparts from other institutions. Eventually, they were willing to work together. But they had to sort out a lot more than simply agreeing to collaborate. How would insurers pay for what they were doing? Would the initial hospital get the money, or would the university hospital? Would malpractice coverage protect doctors outside their own institutions? What about transport?

Every question could be turned into a reason for hospital administrators and lawyers to say no.

. . .

(p. 29) The economics of ECPR are in line with those of other established lifesaving interventions, like dialysis and heart transplants. And if patients don’t survive, ECPR may perfuse their bodies with enough oxygen to keep their organs eligible for donation. The program in Minnesota costs about $3.2 million a year to operate, which is covered by its revenue. This doesn’t include the start-up funding from the Helmsley Trust, however, or the significant groundwork Yannopoulos laid before that — or his personal sacrifices. “When I started, I had hair and my beard was black,” says Yannopoulos, who is mostly bald and gray. For seven years, he was not paid for his ECPR work; some years, he was on call every day. Today, he still spends about 6,500 hours on call annually. “It’s the force of his will more than anything,” Hereford says when explaining why the program has succeeded.

. . .

Yannopoulos has invited physicians from all over to visit his program; afterward, he often hears from them that replicating his work at their home institutions — getting health and E.M.S. systems to collaborate, finding institutional support and start-up funding, coordinating 24/7 staffing — seems too daunting. For these reasons, Yannopoulos regards his ECPR program as “an administrative and political achievement, rather than a scientific or technological one.”

. . .

(p. 30) The trial, called INCEPTION, compared ECPR with standard care across 10 medical centers in the Netherlands. It was the first randomized, controlled trial to look at ECPR across multiple facilities, and unlike the ARREST trial, it found that ECPR resulted in similar survival as standard treatments.  . . .

Yet there are reasons to interpret the study as saying more about the real-world challenges of developing and implementing ECPR programs than it does about the treatment itself. In the INCEPTION trial, it took roughly a half-hour longer for patients to get on an ECMO machine once they arrived at the hospital than it did in the ARREST study. Of the patients who got ECPR, 12 percent were not successfully connected to the machines, compared with zero in ARREST. Several Dutch hospitals handled only a couple of ECPR cases a year, which means they hadn’t yet acquired the right skills. “I think they were destined for failure because of that rollout, with no experience up front,” Bartos says.

Experience matters profoundly: According to a 2022 paper based on data from the Extracorporeal Life Support Organization, an international nonprofit that Robert Bartlett founded, patients treated at centers that perform fewer than 10 ECPR procedures yearly have 64 percent lower odds of survival; for every 10-case increase, the odds go up 11 percent. (The Minnesota program treats about 150 every year.)

Not only does the procedure itself require mastery, but so, too, does the care in the I.C.U. afterward — an ineffable art as much as a precise science.

. . .

(p. 45) . . . it’s not much of a surprise to hear Yannopoulos ask, “What does INCEPTION have to do with what we’re doing?” His program was carefully developed, with deep expertise, over years, to achieve the best outcomes; INCEPTION studied what would happen if a lot of hospitals started doing ECPR tomorrow.

Engineering the ideal ECPR program can feel like a maddening calculus involving experience, availability and distance — all to beat time. To treat patients faster, maybe doctors should go directly to the scene. For more than a decade, doctors in France have been doing just that, performing ECPR on the streets of Paris, in Métro stations, even on the oak parquet floors of the Louvre. Early on, Lionel Lamhaut, the head of Paris’s ECMO team, was told that he was “a cowboy to try to do something outside the hospital.” But as he and his colleagues persisted, they “started a new way of thinking.”

. . .

. . . as much money as the Helmsley Trust has given, it is not enough to overcome some of the structural limitations in the American health care system. The organization funded a multimillion-dollar expansion of the cardiovascular I.C.U. at Yannopoulos’s hospital to add 12 more spacious rooms specifically designed to accommodate patients on ECMO. But on a weekend in January when I visited, the I.C.U. was closed to new ECPR patients: Not enough nurses were available to work, so four beds in the unit were kept empty.

Even as Yannopoulos and his team hit administrative roadblocks like these, they are still trying to redefine what is medically possible. Recently, a 74-year-old man collapsed on the streets of St. Paul and went into cardiac arrest. Forty-two minutes after the first 911 call, the man was already on ECMO and had regained his pulse. Yannopoulos was optimistic about the case, given how quickly ECMO was started, even though the patient had not been shocked with a defibrillator — which meant he technically fell outside the protocol and should not have received ECPR at all. (After a week in the I.C.U., the man died when his family decided to stop all treatment.)

The man’s heart was almost certainly in pulseless electrical activity (P.E.A.), which many experts think should not be treated with ECPR. Of the three published ECPR randomized, controlled trials, only one did not limit the intervention to people with shockable rhythms. That ambitious trial, in Prague, included patients whose hearts were in the same P.E.A. pattern as the St. Paul man’s. The study was stopped early when it appeared that ECPR wasn’t saving significantly more people than standard care was. These enigmatic cases that lack shockable rhythms are vexing: When the Prague data was reanalyzed without these patients, the findings were favorable for ECPR.

Yannopoulos is undeterred by the Prague results. “You have to decide what’s more important: your survival rate” — what is often used in studies and by institutions to justify support for a program — “or the number of patients you actually save.” Because its program is now well established, Yannopoulos’s team is starting to treat patients with less promising rhythms, even though that may drive down its overall survival rate.  . . .

Yannopoulos wonders if, in a decade or perhaps less, ECPR science will still require the same specially trained teams using the same high-tech equipment — at least before patients get to the hospital. Instead, he imagines small cannulas that will be easy to place in the patient’s neck and attached to compact, simple machines that provide some blood flow to the brain. In his vision, which he is currently working to realize, medics could be trained to start people on this, and then doctors could transition them to regular ECMO once they reach the hospital. If the brain is protected, the rest of the body can eventually recover.

. . .

“There is this idea that people in cardiac arrest, you cannot harm them,” Yannopoulos says. For some doctors, that means cycling relentlessly through chest compressions and medications, so they feel as if they did everything they could. For others, it means briefly going through the motions, so they feel as if they did something. And for still others, it has always seemed kindest to do nothing at all, to let their patients die peacefully. Because almost none of them lived — no matter what the doctors did. “But now we know what is possible,” Yannopoulos says. “So if you’re not achieving that, then you are harming them in a way, right?”

For the full story see:

Helen Ouyang. “Reinventing CPR.” The New York Times Magazine (Sunday, March 31, 2024): 22-31 & 45.

(Note: ellipses added.)

(Note: the online version of the story was updated June [sic] 19, 2024, and has the title “The Race to Reinvent CPR.”)

Some references relevant to my discussion at the start of this entry are:

Bush, Jonathan, and Stephen Baker. Where Does It Hurt?: An Entrepreneur’s Guide to Fixing Health Care. New York: Portfolio, 2014.

DeVita, Vincent T., and Elizabeth DeVita-Raeburn. The Death of Cancer: After Fifty Years on the Front Lines of Medicine, a Pioneering Oncologist Reveals Why the War on Cancer Is Winnable–and How We Can Get There. New York: Sarah Crichton Books, 2015.

Diamond, Arthur M., Jr. Openness to Creative Destruction: Sustaining Innovative Dynamism. New York: Oxford University Press, 2019.

Klein, Gary A. Seeing What Others Don’t: The Remarkable Ways We Gain Insights. Philadelphia, PA: PublicAffairs, 2013.

Klein, Gary A. Sources of Power: How People Make Decisions. 20th Anniversary ed. Cambridge, MA: The MIT Press, 2017.

Klein, Gary A. Streetlights and Shadows: Searching for the Keys to Adaptive Decision Making. Cambridge, MA: The MIT Press, 2009.

Koch, Charles G. The Science of Success: How Market-Based Management Built the World’s Largest Private Company. Hoboken, NJ: Wiley & Sons, Inc., 2007.

Silberner, Joanne. “How a Plunger Improved CPR.” The New York Times (Tues., June 27, 2023): D5.

Taleb, Nassim Nicholas. Skin in the Game: Hidden Asymmetries in Daily Life. New York: Random House, 2018.

Vardi, Nathan. For Blood and Money: Billionaires, Biotech, and the Quest for a Blockbuster Drug. New York: W. W. Norton & Company, 2023.

Is Longevity Constrained by Nature or by Government Regulations?

I am a longevity optimist. If regulatory constraints are loosened, I believe entrepreneurs will bring us quicker progress.

(p. A12) S. Jay Olshansky, who studies the upper bounds of human longevity at the University of Illinois Chicago, believes people shouldn’t expect to live to 100.

. . .

Kaare Christensen, co-author of a paper predicting most newborns born in the 2000s would live to 100 if medical progress continued, said it is too soon to know who is right. Future advances could make up for stalled life expectancy gains.

“The setback could be temporary,” he said.

Christensen, who runs studies on very old people at the Danish Aging Research Center in Denmark, said people in their 90s have better cognitive function and healthier teeth over their lifetimes than counterparts of the same age born just 10 years earlier.

“I would say prepare for your 90s instead,” Christensen said.

Old-age debate

Olshansky’s foray into the limits of lifespan began in 1990 when he published a paper in Science stating that life expectancy wouldn’t rise dramatically even if diseases including cancer and heart disease are eliminated. He has been fighting about it ever since.

James Vaupel, a demographer, pushed back. In a 2021 paper, Vaupel pointed to statistics showing that since around 1840 life expectancy at birth has increased almost 2.5 years per decade in some countries.

Vaupel and Olshansky published dueling papers over the decades until Vaupel’s death at age 76 in 2022.

Steven Austad, a professor of biology at the University of Alabama at Birmingham, was asked at a 2001 scientific meeting when he thought the first person to live to 150 would be born. “I think that person is already alive,” Austad replied. Austad said he based his answer on optimism that scientists will figure out how to change the biology of aging.

When Olshansky heard about the exchange, he bet Austad that wasn’t true. In 150 years, he argued, there still wouldn’t be a person alive at 150. The men wagered $150 each, which they put in a fund to pay out in 150 years, with the winner’s heirs to reap the profit. A decade ago, they each added another $150 to the account.

Austad said he agreed with Olshansky that most newborns born now won’t live to 100. But he thinks his optimism that someone will live to 150 is justified. He pointed to a study showing the compound rapamycin extended the lifespan of mice, even if they start getting it later in life. Some longevity enthusiasts are taking rapamycin themselves. Studies on other potentially antiaging compounds are under way.

“If any turn out to work,” Austad said, “they will win my bet for me.”

For the full story see:

Amy Dockser Marcus. “Live Until 100? Our Chances Are Slim.” The Wall Street Journal (Wednesday, July 17, 2024): A12.

(Note: ellipsis added.)

(Note: the online version of the story has the date July 11, 2024, and has the title “Think You Will Live to 100? These Scientists Think You’re Wrong.”)

The paper co-authored by Christensen and mentioned above, is:

Christensen, Kaare, Gabriele Doblhammer, Roland Rau, and James W. Vaupel. “Ageing Populations: The Challenges Ahead.” Lancet 374, no. 9696 (Oct. 3, 2009): 1196-208.

The 2021 paper co-authored by Vaupel and mentioned above, is:

Vaupel, James W., Francisco Villavicencio, and Marie-Pier Bergeron-Boucher. “Demographic Perspectives on the Rise of Longevity.” Proceedings of the National Academy of Sciences 118, no. 9 (2021): e2019536118.

$6 Billion of Taxpayer Money Wasted in 2021 for Bogus Hospital “Facility” Fees Where No Hospital Facility Was Used

The complexity, opaqueness, arbitrariness, and conflicts of interest of government healthcare, as exemplified by Medicare, make it rife for several kinds of inefficiency and fraud. The passages quoted below, document one kind.

(p. B4) Hospitals are adding billions of dollars in facility fees to medical bills for routine care in outpatient centers they own. Once an annoyance, the fees are now pervasive, and in some places they are becoming nearly impossible to avoid, data compiled for The Wall Street Journal show. The fees are spreading as hospitals press on with acquisitions, snapping up medical groups and tacking on the additional charges.

The fees raise prices by hundreds of dollars for widely used and standard medical care, including colonoscopies, mammograms and heart screening.

The added cost isn’t justified, physicians and economists say. Medicare advisers said last year the federal insurer likely overpaid for a sample of services by about $6 billion because of the fees in 2021.

. . .

The fees show up on patients’ bills after hospitals snap up clinics and doctors. Hospitals can designate the newly acquired clinics as an extension of their operations, forcing patients to pay the fees to cover costs for the entire hospital.

Fees have grown more pervasive as hospitals have gone on an acquisition tear in recent years, chasing after patients who have more options to get medical care somewhere else. Many hospital systems now get at least half their revenue from patients who aren’t admitted. By one estimate, more than half of doctors work for hospitals.

For the full story see:

Melanie Evans. “Patients Rack Up Hidden Hospital Fees.” The Wall Street Journal (Tuesday, March 26, 2024): B4.

(Note: ellipsis added.)

(Note: the online version of the story has the date March 25, 2024, and has the title “Hospitals Are Adding Billions in ‘Facility’ Fees for Routine Care.”)

Federal Government Creates Perverse Incentives for Medical Insurers to Harvest Diagnoses for Untreated Maladies in the So-Called Medical “Advantage” Program

Notice that the federal government has set up the incentives of the Medicare Advantage program so that insurers will receive benefits, but no costs, for diagnosing patients with certain conditions, that the patients have not asked them to treat. The nurse home visits aimed at harvesting diagnoses do not benefit patients, but instead waste patients’ time and taxpayers’ money. Is UnitedHealth Group the most despicable organization for shamelessly exploiting the perverse incentives, or is the federal government the most despicable organization for creating the perverse incentives?

(p. A3) Millions of times each year, insurers send nurses into the homes of Medicare recipients to look them over, run tests and ask dozens of questions.

The nurses aren’t there to treat anyone. They are gathering new diagnoses that entitle private Medicare Advantage insurers to collect extra money from the federal government.

A Wall Street Journal investigation of insurer home visits found the companies pushed nurses to run screening tests and add unusual diagnoses, turning the roughly hourlong stops in patients’ homes into an extra $1,818 per visit, on average, from 2019 to 2021. Those payments added up to about $15 billion during that period, according (p. A9) to a Journal analysis of Medicare data.

Nurse practitioner Shelley Manke, who used to work for the HouseCalls unit of UnitedHealth Group, was part of that small army making home visits. She made a half-dozen or so visits a day, she said in a recent interview.

Part of her routine, she said, was to warm up the big toes of her patients and use a portable testing device to measure how well blood was flowing to their extremities. The insurers were checking for cases of peripheral artery disease, a narrowing of blood vessels. Each new case entitled them to collect an extra $2,500 or so a year at that time.

But Manke didn’t trust the device. She had tried it on herself and had gotten an array of results. When she and other nurses raised concerns with managers, she said, they were told the company believed that data supported the tests and that they needed to keep using the device.

“It made me cringe,” said Manke, who stopped working for HouseCalls in 2022. “I didn’t think the diagnosis should come from us, period, because I didn’t feel we had an adequate test.”

. . .

Last month, the Journal reported that insurers received nearly $50 billion in payments from 2019 to 2021 due to diagnoses they added themselves for conditions that no doctor or hospital treated. Many of the insurer-driven diagnoses were outright wrong or highly questionable, the Journal found.

. . .

In the Medicare Advantage system—conceived as a lower-cost alternative to traditional Medicare—private insurers get paid a lump sum to provide health benefits to about half of the 67 million seniors and disabled people in the federal program. The payments go up when people have certain diseases, giving insurers an incentive to diagnose those conditions.

To find out how insurers use home visits to add diagnoses, the Journal interviewed nurses, patients, home-visit managers and industry executives and reviewed hundreds of pages of internal documents from home-visit companies. They described a system that used nurses, software and audits to generate diagnoses.

“They do the job with a purpose, and it pays off for the Medicare Advantage plans,” said Francois de Brantes, a former executive at Signify Health, a company that does home visits for insurers. “Identifying the diagnoses, that’s the job.”

. . .

Secondary hyperaldosteronism, a condition in which levels of the hormone aldosterone rise, is rarely diagnosed in traditional Medicare patients. HouseCalls documents show that its software would suggest the diagnosis if a patient had a history of heart failure or cirrhosis, and either took certain drugs, such as diuretics, or had swelling due to fluid retention. Nurses weren’t required to confirm the diagnosis with a lab test.

“In a million years, I wouldn’t have come up with a diagnosis of secondary hyperaldosteronism,” said Bell, the former HouseCalls nurse.

UnitedHealth diagnosed it 246,000 times after home visits, leading to $450 million in payments over the three years of the Journal’s analysis. All other Medicare insurers combined collected $42 million from making that diagnosis after home visits.

For the full story see:

Anna Wilde Mathews, Christopher Weaver, Tom McGinty and Mark Maremont. “Nurse Visits Made Insurers $15 Billion.” The Wall Street Journal (Tuesday, Aug. 6, 2024): A1 & A9.

(Note: ellipses added.)

(Note: the online version of the story has the date August 4, 2024, and has the title “The One-Hour Nurse Visits That Let Insurers Collect $15 Billion From Medicare.”)

Healthcare Competition Sometimes Reduces Prices

Numerous complex government healthcare regulations differentially increase the costs of small healthcare firms and independent healthcare practitioners that cannot afford to hire the specialized experts to understand and navigate the regulations. As a result the small firms and independent practitioners often give up and merge with larger organizations, thereby reducing competition. Also, in many locations, governments give incumbent hospitals veto power over the start-up of new hospitals, thereby also reducing competition.

(p. A3) Prices for surgery, intensive care and emergency-room visits rise after hospital mergers. The increases come out of your pay.

Hospitals have struck deals in recent years to form local and regional health systems that use their reach to bargain for higher prices from insurers. Employers have often passed the higher rates onto employees.

Such price increases added an average of $204 million to national health spending in the year after mergers of nearby hospitals, according to a study published Wednesday [April 24, 2024] by American Economic Review: Insights.

Workers cover much of the bill, said Zack Cooper, an associate professor of economics at Yale University who helped conduct the study. Employers cut into wages and trim jobs to offset rising insurance premiums, he said. “The harm from these mergers really falls squarely on Main Street,” Cooper said.

For the full story see:

Melanie Evans. “Hospital Prices Rise After Mergers, and Patients Bear Brunt.” The Wall Street Journal (Thursday, April 25, 2024): A3.

(Note: bracketed date added.)

(Note: the online version of the story was updated April 24, 2024, and has the title “The True Cost of Megamergers in Healthcare: Higher Prices.” The online version says that the title of the print version was “Hospital-Care Prices Rise After Mergers.” But my national edition of the print version had the title “Hospital Prices Rise After Mergers, and Patients Bear Brunt.”)

The forthcoming article co-authored by Cooper, and mentioned above, is:

Brot-Goldberg, Zarek, Zack Cooper, Stuart Craig, and Lev Klarnet. “Is There Too Little Antitrust Enforcement in the U.S. Hospital Sector?” American Economic Review: Insights (forthcoming).

Low Government-Negotiated Drug Prices Will Slash Pharma Revenue Needed to Finance Government-Mandated Costly Phase 3 Trials

Mandated Phase 3 randomized double-blind clinical trials cost many millions of dollars each, and most of the trials fail. To fund all the trials that fail and the few that succeed, the few new drugs that succeed need to have high price tags. The only other way for new drug development to be economically sustainable, is to stop mandating Phase 3 clinical trials. If we stopped mandating Phase 3 clinical trials, we would, in other words, allow physicians and patients to try drugs after safety has been shown through Phase 1 and Phase 2 trials, but without the expensive proof of efficacy from Phase 3 trials. We would thereby allow physicians and patients greater freedom.

(p. B6) While many companies, from Pfizer to Bristol-Myers Squibb to Bayer and Novartis, have announced big layoffs, news from a key outsourcer on Wednesday [Aug. 7, 2024] showed that the industry’s cost-cutting ways are intensifying.

Charles River Laboratories International, which provides drug-development services, plunged 12.6% on Wednesday [Aug. 7, 2024], the most in four years, after sounding the alarm over pharma research spending plans. The Massachusetts-based company said it now expects to post a decline in sales for the full year, primarily owing to lower demand from pharma clients. The company previously expected to grow this year. “There are profound cuts at pharmaceutical companies,” James Foster, Charles River’s chief executive officer, told analysts. Foster called the reduction in pharma research spending “unusual” and “sudden.”

Foster said his clients are blaming the cuts on the Inflation Reduction Act, which allows Medicare to negotiate some drug prices directly with manufacturers, and a looming patent cliff, which will see more than $200 billion in annual drug sales come under threat from copycat generics.

For the past few years, pharma companies have been warning that they might need to cut back on innovation as the U.S. government forces some companies to negotiate prices of their top-selling drugs.

. . .

A reduction in preclinical testing, the kind of services that Charles River provides, is the sort of thing that will only be felt in the long term. By that time, current management teams, desperate to lift their stocks now, might be long gone.  . . .

Big pharma wants to clean house. Expensive studies of drugs that won’t make it to market for many years to come are an easy target.

For the full commentary see:

David Wainer. “Big Pharma Scales Back R&D, Sending Shudders Through Industry.” The Wall Street Journal (Friday, Aug. 9, 2024): B6.

(Note: ellipses, and bracketed dates, added.)

(Note: the online version of the commentary has the date August 8, 2024, and has the title “Big Pharma Cuts R&D, Sending Shudders Through Industry.” The quoted paragraph starting with “Foster said” appears in the online, but not the print, version of the commentary.)

The New York Times Is Open to the Possibility and Desirability of Geoengineering

In the past, The New York Times either ignored, or was dismissive of, geoengineering to reverse or mitigate the alleged future effects of global warming. A few months ago, I was pleasantly surprised to see the paper publish a page one article, quoted below, that was open to the policy of geoengineering. This is progress because the left’s standard response to the alleged effects of global warming is to advocate reduced economic growth. Geoengineering would allow economic growth, and the human flourishing it allows, to continue, even if global warming becomes as severe as the pessimists fear.

(p. 1) On a windswept Icelandic plateau, an international team of engineers and executives is powering up an innovative machine designed to alter the very composition of Earth’s atmosphere.

If all goes as planned, the enormous vacuum will soon be sucking up vast quantities of air, stripping out carbon dioxide and then locking away those greenhouse gases deep underground in ancient stone — greenhouse gases that would otherwise continue heating up the globe.

Just a few years ago, technologies like these, that attempt to re-engineer the natural environment, were on the scientific fringe. They were too expensive, too impractical, too sci-fi. But with the dangers from climate change worsening, and the world failing to meet its goals of slashing greenhouse gas emissions, they are quickly moving to the mainstream among both scientists and investors, despite questions about their effectiveness and safety.

. . .  Once science fiction, today these ideas are becoming reality.

Researchers are studying ways to block some of the sun’s radiation. They are testing whether adding iron to the ocean could carry carbon dioxide to the sea floor. They are hatching plans to build giant parasols in space. And with massive facilities like the one in Iceland, they are seeking to reduce the concentration of carbon dioxide in the air.

. . .

(p. 12) A plant similar to the one in Iceland, but far larger, is being built in Texas by Occidental Petroleum, the giant oil company.

. . .

The Occidental plant, being built near Odessa, Texas, and known as Stratos, will be more than 10 times more powerful than Mammoth, powered by solar energy, and have the potential to capture and sequester 500,000 metric tons of carbon dioxide per year.

It uses a different process to extract carbon dioxide from the air, though the goal is the same: Most of it will be locked away deep underground. But at least some of the carbon dioxide, Occidental says, will also be used to extract more oil.

In that process, carbon dioxide is pumped into the ground to force out oil that might otherwise be too difficult to reach. Techniques like this have made Occidental a company worth more than $50 billion and helped send American crude production to a new high in recent years.

Of course, it is the world’s reliance on the burning of oil and other fossil fuels that has so dangerously sent carbon dioxide levels soaring. In the atmosphere, carbon dioxide acts as a blanket, trapping the sun’s heat and warming the world.

Today, Occidental says it is trying to become a “carbon management” company as well as an oil producer. Last year, it paid $1.1 billion for a start-up called Carbon Engineering that had developed a way to soak up carbon dioxide from the air, and began building the Stratos project. Today, what was a barren plot of dirt less than 12 months ago is a bustling construction site.

“It’s like the Apollo missions at NASA,” said Richard Jackson, who oversees carbon management and domestic oil operations at Occidental. “We’re trying to move as quickly as we can.”

For the full story see:

David Gelles. “Can We Engineer Our Way Out of a Climate Crisis?” The New York Times, First Section (Sunday, March 31, 2024): 1 & 12-13.

(Note: ellipses added.)

(Note: the online version of the story was updated April 4, 2024, and has the title “Can We Engineer Our Way Out of the Climate Crisis?” The sentence above that starts “Once science fiction” appeared in the print, but not the online, version.)

Prepare for Next Unexpected Disaster By Unbinding Nimble Entrepreneurs Who Can Pivot and Improvise

Governments have trouble preparing for uncertain and rare disasters, such as pandemics. So they “fight the last war,” expecting that the next disaster will look like the last disaster. Before WWII, France built the Maginot line, which they thought would have protected them against the kind of attack they had faced in WWI. The U.S. was more prepared for an Ebola pandemic than for a Covid pandemic. In an uncertain world, the best way to prepare for rare disasters is to allow and encourage nimble entrepreneurs who can resiliently pivot and improvise to counter whatever disaster arrives.

(p. A8) Britain’s government “failed” the country’s citizens in its handling of the coronavirus pandemic, a damning report from an official public inquiry said on Thursday [July 18, 2024], partly because officials had prepared for “the wrong pandemic.”

The arrival of Covid-19 in 2020 exposed flaws in Britain’s public health system and its pandemic preparedness that had been ignored for years, the report said. During the early waves of infections, Britain’s per capita death rate was among the highest in Europe, eventually leading to more than 225,000 deaths in total, according to official data.

“Had the U.K. been better prepared for and more resilient to the pandemic, some of that financial and human cost may have been avoided,” the report said.

. . .

Britain had a plan, but it was “outdated and lacked adaptability,” the report said.

It was also too focused on the possibility of a flu pandemic. “Although it was understandable for the U.K. to prioritize pandemic influenza, this should not have been to the effective exclusion of other potential pathogen outbreaks,” the report said.

. . .

Ministers, who are political appointees, did not have access to a broad enough range of scientific research and opinions that would have informed their policies, and advisers did not feel confident about expressing dissenting views.

“The advice offered to ministers and international bodies may well have been affected by a degree of ‘groupthink’,” the report said.

For the full story see:

Lynsey Chutel. “Before Covid, U.K. Prepared for ‘the Wrong Pandemic,’ Inquiry Finds.” The New York Times (Monday, July 22, 2024): A8.

(Note: ellipses, and bracketed date, added.)

(Note: the online version of the story has the date July 18, 2024, and has the title “U.K. Failed in Handling of Covid Pandemic, Inquiry Finds.”)

The “damning report” mentioned above, is:

Hallett, Baroness. “Uk Covid-19 Inquiry; Module 1: The Resilience and Preparedness of the United Kingdom.” July 18, 2024.

The “Innovative Approach” of the Dog Aging Project May Have Hurt Its Odds for Renewed Funding

Veterinary medicine is less regulated than human medicine, and so trial and error experiments may allow faster innovation that would benefit both dogs and humans.

(p. D3) In late 2019, scientists began searching for 10,000 Americans willing to enroll their pets in an ambitious new study of health and longevity in dogs. The researchers planned to track the dogs over the course of their lives, collecting detailed information about their bodies, lifestyles and home environments. Over time, the scientists hoped to identify the biological and environmental factors that kept some dogs healthy in their golden years — and uncover insights about aging that could help both dogs and humans lead longer, healthier lives.

Today, the Dog Aging Project has enrolled 47,000 canines and counting, and the data are starting to stream in. The scientists say that they are just getting started.

“We think of the Dog Aging Project as a forever project, so recruitment is ongoing,” said Daniel Promislow, a biogerontologist at the University of Washington and a co-director of the project. “There will always be new questions to ask. We want to always have dogs of all ages participating.”

But Dr. Promislow and his colleagues are now facing the prospect that the Dog Aging Project might have its own life cut short. About 90 percent of the study’s funding comes from the National Institute on Aging, a part of the National Institutes of Health, which has provided more than $28 million since 2018. But that money will run out in June, and the institute does not seem likely to approve the researchers’ recent application for a five-year grant renewal, the scientists say.

“We have been told informally that the grant is not going to be funded,” said Matt Kaeberlein, the other director of the Dog Aging Project and a former biogerontology researcher at the University of Washington. (Dr. Kaeberlein is now the chief executive of Optispan, a health technology company.)

. . .

Steven Austad, a biogerontologist at the University of Alabama at Birmingham who is not part of the research team, said he was surprised that the researchers’ grant might not be renewed. “The importance of the things they publish and the depth of detail will increase over time, but I thought they got off to a really good start,” he said. “A large study like this really deserves a chance to mature.”

Dr. Austad’s miniature dachshund, Emmylou, is enrolled in the Dog Aging Project. But at 2 years old, he noted, Emmylou is “not going to teach them a lot about aging for a long time yet.”

The project’s innovative approach might have worked against it, Dr. Austad added. Reviewers accustomed to evaluating short-term research on lab mice and long-term studies of humans may not have known what to make of an enormous epidemiological study of pet dogs.

Whatever the reason, the refusal to commit to more funding is “wrong,” Dr. Kaeberlein said. “It’s just really, really difficult to justify this decision, if you look at the productivity and the impact of the project.”

That impact extends beyond the findings themselves, he added. “This project has engaged almost 50,000 Americans in biomedical scientific research.”

Over the last few years, Shelley Carpenter, of Gulfport, Miss., has provided the researchers with regular updates on and medical records for her Pembroke Welsh corgi, Murfee. (She also collected a cheek swab for genomic sequencing.) Ms. Carpenter, whose previous corgi died from a neurodegenerative disease similar to A.L.S., hoped that the project might produce new medical knowledge that could help both dogs and people.

For the full story see:

Emily Anthes. “Scientists Scramble to Keep Dog Aging Project Alive.” The New York Times (Tuesday, January 16, 2024): D3.

(Note: ellipses added.)

(Note: the online version of the story has the date Jan. 11, 2024, and has the same title as the print version.)

Sweden’s Restraint in Mandating Covid Lockdowns Resulted in Much Lower Excess Mortality Than the U.S. Suffered

(p. A17) The best measure of health performance during the pandemic is all-cause excess mortality, which captures the overall number of deaths relative to the expected level, encompassing Covid and lockdown-related deaths. On this measure Sweden—which kept most schools open and avoided strict lockdown orders—outperformed nearly every country in the world.

A recent study published in the Proceedings of the National Academy of Sciences found that the U.S. “would have had 1.60 million fewer deaths if it had the performance of Sweden, 1.07 million fewer deaths if it had the performance of Finland, and 0.91 million fewer deaths if it had the performance of France.” In America, states that imposed prolonged lockdowns had no better health outcomes when measured by all-cause excess mortality than those that stayed open. While no quantifiable relationship between lockdown severity and a reduction in Covid health harms has been found, states with severe lockdowns suffered significantly worse economic outcomes.

. . .

The economic costs of lockdowns were also staggering. According to the Bureau of Labor Statistics, as many as 49 million Americans were out of work in May 2020. This shock had health consequences. A National Bureau of Economic Research study found that the lockdown unemployment shock is projected to result in 840,000 to 1.22 million excess deaths over the next 15 to 20 years, disproportionately killing women and minorities.

For the full commentary see:

Scott W. Atlas and Steve H. Hanke. “Covid Lessons Learned, Four Years Later.” The Wall Street Journal (Tuesday, March 19, 2024): A17.

(Note: ellipsis added.)

(Note: the online version of the commentary has the date March 18, 2024, and has the same title as the print version.)

The “recent study” mentioned above is:

Ioannidis, John P. A., Francesco Zonta, and Michael Levitt. “Variability in Excess Deaths across Countries with Different Vulnerability During 2020–2023.” Proceedings of the National Academy of Sciences 120, no. 49 (Dec. 5, 2023): e2309557120.

The published version of the National Bureau of Economic Research study mentioned above is:

Bianchi, Francesco, Giada Bianchi, and Dongho Song. “The Long-Term Impact of the Covid-19 Unemployment Shock on Life Expectancy and Mortality Rates.” Journal of Economic Dynamics and Control 146 (Jan. 2023): 104581.

Fingarette Provoked Thought on Alcohol and Death

When I was a graduate student in the late 1970s I attended a small seminar in Santa Barbara presented by Henry Fingarette on his thoughts on alcoholism. I do not know if I agree with those thoughts, or his thoughts on death, mentioned in the obituary quoted below. But I enjoyed his non-politically-correct seminar and still find his thoughts on both topics to be worth pondering. [I participated in the seminar as part of a month or two residency in Santa Barbara organized by the philosopher Tibor Machan and funded by the Reason Foundation. Other participants included David Levy, Doug Rasmussen, and Doug Den Uyl. Gary Becker told me that it was a mistake for me to attend; he said those weeks would be better spent staying in Chicago and improving my math skills. Becker’s advice was sincere and well-intentioned, but even now I am conflicted on whether I should have followed his advice.]

(p. 26) Herbert Fingarette, a contrarian philosopher who, while plumbing the perplexities of personal responsibility, defined heavy drinking as willful behavior rather than as a potential disease, died on Nov. 2 at his home in Berkeley, Calif. He was 97.

. . .

In “Heavy Drinking: The Myth of Alcoholism as a Disease” (1988), Professor Fingarette all but accused the treatment industry of conspiring to profit from the conventional theory that alcoholism is a disease. He maintained that heavy use of alcohol is a “way of life,” that many heavy drinkers can choose to reduce their drinking to moderate levels, and that most definitions of the word “alcoholic” are phony.

“Some people can drink very heavily and get into no trouble whatsoever,” he told The New York Times in 1989.

. . .

At his death, he was completing an essay on how the dead continue to shape the lives of the living, a topic he had written about in “Death: Philosophical Soundings” (1996). . . .

“Never in my life will I experience death,” he wrote. “I will never know an end to my life, this life of mine right here on earth.” He added: “People hope never to know the end of consciousness. But why merely hope? It’s a certainty. They never will!”

For the full obituary, see:

Sam Roberts. “Herbert Fingarette, 97, Contrarian on Alcoholism.” The New York Times, First Section (Sunday, November 18, 2018 [sic]): 26.

(Note: ellipses added.)

(Note: the online version of the obituary has the date Nov. 15, 2018 [sic], and has the title “Herbert Fingarette, Contrarian Philosopher on Alcoholism, Dies at 97.”)

Fingarette’s book on alcoholism, mentioned above, is:

Fingarette, Herbert. Heavy Drinking: The Myth of Alcoholism as a Disease. Berkeley, CA: University of California Press, 1989.

Fingarette’s book on death, mentioned above, is:

Fingarette, Herbert. Death: Philosophical Soundings. Chicago: Open Court, 1999.