Category: Regulations

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.

When Medical Insurers Own Doctor Practices, Medicare Advantage Creates “Conflicts of Interest and Opportunities to Game the System”

Through its Optum division health insurer UnitedHealth has 90,000 affiliated doctors. Under the federal government’s Medicare Advantage program, UnitedHealth received higher payments from the federal government for its customers who have more dire diagnoses. This creates an incentive for UnitedHealth to pressure its affiliated doctors to code their patients with dire diagnoses.

(p. A3) UnitedHealth has built a sprawling health services company that shows no sign of slowing down. With annual revenue of $372 billion in 2023, it ranks among the five largest companies in the U.S. on that measure. Its stock, meanwhile, has returned more than 600% in the past decade.

UnitedHealth’s success has been fueled by its expansion beyond insurance as its care delivery and solutions unit Optum steadily acquires a vast array of health services companies, from a pharmacy-benefits manager to specialty pharmacies to doctor groups and surgical centers. Over the past two decades, Optum has spent about $82 billion on nearly 100 acquisitions, according to a tally by Raymond James analysts.

Much like the rest of the U.S. economy, America’s healthcare system has consolidated in recent decades, creating giant hospital systems, chain-owned medical practices and vertically integrated insurance conglomerates. Immense scale can drive efficiencies and reduce the cost of care. But in the highly complex and opaque world of U.S. healthcare, where giant companies always seem to be a step ahead of regulators, it also raises potential conflicts of interest and opportunities to game the system. The benefits of size often flow to those companies, not patients or the employers and taxpayers footing much of the bill.

. . .

A key growth driver for UnitedHealth is Optum’s steady acquisitions of doctor practices. Optum now has ties with 90,000 doctors—about 10% of the country’s physician workforce.

. . .

Much of the vertical integration in the industry has focused on the Medicare Advantage business, the sector’s golden goose. These are the private plans in which the government pays insurers a fixed rate to manage the care of seniors. The sicker the patient, the more the government pays.

In recent years, some insurers’ acquisitions seem targeted at controlling the Medicare coding apparatus. If you control the doctors who code patients, you control how much you get paid, explains Loren Adler, a fellow at the Center on Health Policy at the Brookings Institution, a nonprofit research organization. UnitedHealth and other insurers argue that they are simply coding patients according to their risk profile and that they comply with Centers for Medicare and Medicaid Services rules.

But they have been accused of abusing the system by coding patients too aggressively. An investigation by the Office of Inspector General of the Department of Health and Human Services found that Medicare insurers received $9 billion in questionable payments in a single year.

For the full commentary see:

David Wainer. “Insurers as Healthcare Providers Risk Conflict of Interest.” The Wall Street Journal (Friday, June 14, 2024): B10.

(Note: ellipses added.)

(Note: the online version of the commentary has the date June 13, 2024, and has the title “What Happens When Your Insurer Is Also Your Doctor and Your Pharmacist.”)

Older Americans, Most at Risk from Covid-19, Were Often Excluded from Mandated Clinical Trials of Therapies and Vaccines

Mandating randomized double-blind clinical trials for Covid-19 candidate therapies or vaccines slowed down the ability of citizens to choose those therapies or vaccines in 2020. Arguably those most hurt by the delay were older Americans age 65 and older, who had the greatest risk of death from Covid-19. The mandated trials slowed availability, but did they at least provide older Americans more and better information about the safety and efficacy of the therapies and vaccines? Not as much as you might suppose. The clinical trials often excluded older Americans because their participation would make the trials more expensive, slower, and less likely to prove safety and efficacy at levels that would result in FDA approval.

(p. D3) “Ideally, the patients enrolled in a randomized clinical trial reflect the demographics of the disease,” said Dr. Mark Sloan, a hematologist leading a Covid-19 drug study at Boston Medical Center, in an email. “Unfortunately, this is seldom the case.”

Now, Dr. Sharon K. Inouye, a geriatrician at Harvard Medical School and Hebrew SeniorLife, is sounding an alarm. She points out that in the race to find drugs and vaccines to fight the pandemic — in which 80 percent of American deaths have occurred in people over age 65 — a substantial proportion of studies may be excluding older subjects, purposely or inadvertently.

“A year from now, when these trials are published, I don’t want to see that there’s no one in them over 75,” she said. “If they create a drug that works really well in healthy 50- and 60-year-olds, they’ve missed the boat.”

She and her team have reviewed 241 interventional Covid-19 studies undertaken in the United States and listed on clinicaltrials.gov, a site maintained by a division of the National Institutes of Health.

They found that 37 of these trials — testing drugs, vaccines and devices — set specific age limits and would not enroll participants older than 75, 80 or 85. A few even excluded those over 65.

. . .

Overall, when Dr. Inouye compiled preliminary results, which have not yet been published, she found that about one-quarter of interventional trials in the United States could exclude or underrepresent older adults.

“To have them be this gravely impacted and not include them is immoral,” said Dr. Louise Aronson, the author of the best-selling book “Elderhood” and a geriatrician at the University of California, San Francisco. “It seems crazy.”

. . .

In clinical trials, “you want to control as many factors as possible,” Dr. Aronson said. Most older adults have other illnesses and take multiple medications, so-called confounding variables that make it difficult to distinguish the effects of the drug or vaccine being studied.

Older people also suffer more side effects. “Nearly all drugs are less toxic when given to younger, healthier people,” Dr. Sloan said in an email. Focusing on them produces fewer adverse effects that must be reported, “and thereby improves chances for F.D.A. approval.”

Physical disabilities, which make it harder for seniors to reach study sites, or hearing and vision impairments requiring large-print forms or audio amplification, can further decrease participation. Investigators may need to take the extra step of obtaining family consent if a patient is incapacitated.

For the full story see:

Paula Span. “The New Old Age; Older Adults May Be Left Out of Some Covid-19 Trials.” The New York Times (Tuesday, June 23, 2020 [sic]): D3.

(Note: ellipses added.)

(Note: the online version of the story has the date June 19, 2020 [sic], and has the same title as the print version.)

After the publication of the NYT article quoted above, Dr. Inouye’s results were published in:

Helfand, Benjamin K. I., Margaret Webb, Sarah L. Gartaganis, Lily Fuller, Churl-Su Kwon, and Sharon K. Inouye. “The Exclusion of Older Persons from Vaccine and Treatment Trials for Coronavirus Disease 2019—Missing the Target.” JAMA Internal Medicine 180, no. 11 (Nov. 2020): 1546-49.

Our Brains Learn in a Process of Continuous Bayesian Updating

(p. A13) First articulated in the 18th century by a hobbyist-mathematician seeking to reason backward from effects to cause, Bayes’ theorem spent the better part of two centuries struggling for recognition and respect. Yet today, argues Tom Chivers in “Everything Is Predictable,” it can be seen as “perhaps the most important single equation in history.” It drives the logic of spam filters, artificial intelligence and possibly our own brains. . . .

At its core, the theorem provides a quantitative method for getting incrementally wiser by continuously updating what you think you know—your prior beliefs, which initially might be subjective—with new information. Your refined belief becomes the new prior, and the process repeats.

. . .

At times Mr. Chivers, a London-based science journalist who now writes for Semafor, seems overwhelmed by an admittedly complex subject, and his presentation lacks the clarity of Sharon Bertsch McGrayne’s “The Theory That Would Not Die” (2011). Yet he is onto something, since Bayes’ moment has clearly arrived. He notes that Bayesian reasoning is popular among “people who come from the new schools of data science—machine learning, Silicon Valley tech folks.” The mathematician Aubrey Clayton tells him that, in the cutting-edge realms of software engineering, “Bayesian methods are what you’d use.”

. . .

It’s notoriously difficult for most people to grasp problems in a structured Bayesian fashion. Suppose there is a test for a rare disease that is 99% accurate. You’d think that, if you tested positive, you’d probably have the disease. But when you figure in the prior—the fact that, for the average person (without specific risk factors), the chance of having a rare disease is incredibly low—then even a positive test means you’re still unlikely to have it. When quizzed by researchers, doctors consistently fail to consider prevalence—the relevant prior—in their interpretation of test results. Even so, Mr. Chivers insists, “our instinctive decision-making, from a Bayesian perspective, isn’t that bad.” And indeed, in practice, doctors quickly learn to favor common diagnoses over exotic possibilities.

. . .

Our brains work by making models of the world, Mr. Chivers reminds us, assessing how our expectations match what we earn from our senses, and then updating our perceptions accordingly. Deep down, it seems, we are all Bayesians.

For the full review, see:

David A. Shaywitz. “Thinking Prior to Thought.” The Wall Street Journal (Thursday, May 15, 2024): A13.

(Note: the online version of the review has the date May 14, 2024, and has the title “‘Everything Is Predictable’ Review: The Secret of Bayes.” In the last quoted sentence I have replaced the word “earn” that appears in both the online and print versions, with the word “learn.”)

The book under review is:

Chivers, Tom. Everything Is Predictable: How Bayesian Statistics Explain Our World. New York: Atria/One Signal Publishers, 2024.