When Ronald Reagan Needed the Owls of Hogwarts

One of my favorite scenes in the first Harry Potter movie is when an owl tries to deliver to Harry Potter an acceptance letter to Hogwarts. Ever since Voldemort murdered Harry’s parents when he was a baby, Harry has lived under a staircase with the Dursleys (Mrs. Dursley was the sister of Harry’s mother). Mr. Dursley, and the other Dursleys too, do not like Harry, hence his living under a staircase. Mr. Dursley sees the letter to Harry, opens it, and when he realizes the contents tears it up. Then a few other copies arrive and Dursley burns them. It would appear that Harry’s hope of escape is dashed.

But then something wonderful. Countless owls fly toward the Dursley house, each carrying copies of the letter. Acceptance letters start pouring through the front door mail slot, down the chimney, and through every opening in the house. Soon the inside of the Dursley house is buried in acceptance letters. Dursley cannot stop Harry from knowing.

I thought of this scene when I was reading the Wikipedia entry for “Human Events.” Human Events was a smallish weekly readers-digest-type newspaper that my father subscribed to for many years (in the 1960s and 1970s?). Copies of Human Events would always be piled up next to his chair in the living room. Human Events was a contrarian publication presenting conservative/libertarian commentaries on the issues of the day.

The Wikipedia article says that starting in 1961, Ronald Reagan is an avid reader of Human Events. In the 1970s he writes articles that appear in Human Events. When he is president, Reagan’s top aides Baker, Darman, and Deaver do not like what is in Human Events, and try to keep copies of it away from him. When Reagan realizes that his aides are blocking Human Events, he “arranged for multiple copies to be sent to the White House residence every weekend” (Edwards 2011, as quoted in Wikipedia entry on “Human Events“).

Unfortunately for Reagan he does not have a flock of wise owls providing redundant information. But Reagan is his own owl.

Harry could not fire Dursley; I wonder why Reagan did not fire Baker, Darman, and Deaver?

Wikipedia gives the source of the Edwards quote as:

Edwards, Lee. “Reagan’s Newspaper.” URL: http://www.humanevents.com/article.php?id=41609

Britain’s Socialized Medicine Can Take Many Hours to Transport Emergency Patients

(p. A1) WREXHAM, Wales — Rachel Parry and Wayne Jones, two paramedics with the Wrexham Ambulance Service, pulled up to a hospital in northern Wales with a patient just after 10 a.m. one early December [2022] morning.

That’s when their wait began.

It would be 4:30 p.m. before their patient, a 47-year-old woman with agonizing back pain and numbness in both of her legs, would be handed over to the emergency room of Wrexham Maelor Hospital. It was more than 12 hours since she had first called 999, the British equivalent of 911.

The delays have grown so bad — and so common — the two paramedics said, that their first interaction with patients is no longer an introduction.

“We start with an apology now,” Ms. Parry said. “Every job is, like, they open the front door, ‘Hi, we are so sorry we are late.’ That has become the norm.”

The sight of ambulances lined up for hours outside hospitals has become distressingly familiar in Wales, which last month recorded its worst wait times ever for life-threatening emergency calls. But the problem is far from isolated. Ambulances services in England, Scotland and Northern Ireland are also experiencing record-high waits.

It’s a near-crisis situation that experts say signals a breakdown of the compact between Britons and their revered National Health Service: that the government will provide responsible, efficient health care services, mostly free, across all income levels.

. . .

(p. A7) While Ms. Parry and Mr. Jones waited at the hospital with their second patient, there were at least 21 calls in their response area that they and other paramedics also stuck at the hospital could not be deployed to. During their 12-hour shift, they picked up only three patients.

“It’s frustrating,” Mr. Jones said. “These people are out in the community and they are desperate.”

Good Samaritans sometimes step in and drive people in distress to the hospitals themselves. While Ms. Parry and Mr. Jones were waiting with their patients, two cars pulled into the ambulance drop-off point with patients. In both cases — one in which an elderly woman fell and broke her wrists and another in which a woman collapsed in a supermarket — the driver had called the emergency services only to be told it would be hours before an ambulance could come.

“Bystanders are doing more jobs than me today,” Ms. Parry said in frustration, after helping both arrivals into the hospital.

. . .

Families also find the long waits excruciating as they watch their loved ones suffer. Frank Taylor waited three hours with his wife Ann Taylor, 79, for an ambulance, saying it was hard for him to see her in so much pain.

When the paramedics arrived, he was relieved to see them swiftly hook her up to oxygen before gently carrying her, wrapped in a blue knit blanket, down the stairs to the ambulance.

But when they reached the hospital, it was another two-hour wait before Ms. Taylor was finally taken inside.

Around 8:30 p.m., Ms. Taylor was transferred from the emergency room to the intensive care unit, the final stop after a long day of uncertainty.

Last year, Ms. Taylor was moved to a nursing home after her health declined — she has end-stage lung disease — and Mr. Taylor visits her daily. It was there that the ambulance picked her up.

. . .

While he praised the care of the paramedics, Mr. Taylor said the wait time was frustrating. He worried about his wife’s dignity during this final stage of her life.

For the full story, see:

Megan Specia. “A Day With a U.K. Ambulance: Painful Waits, Crowded Hospitals.” The New York Times (Wednesday, December 21, 2022 [sic]): A1 & A7.

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

(Note: the online version of the story was updated Dec. 22, 2022 [sic], and has the title “One Day With an Ambulance in Britain: Long Waits, Rising Frustration.”)

The Lovable, Frustrating, Vulnerable “Big Easy”

Our daughter is a loyal Notre Dame graduate, so we went to New Orleans for the Sugar Bowl game, scheduled for January 1, but ultimately played on January 2. The day before the scheduled game, we were in Jackson Square on New Year’s Eve for the countdown to 2025. For us a little partying goes a long way, so we headed back to the Marriott about 12:30. About two and a half hours later, a couple of blocks from where we had been, the terrorist plowed his truck through the crowd, killing 14, and seriously injuring many more.

They call New Orleans “the Big Easy.” I appreciate its joy, its spontaneity, its libertarian tolerance. But I can only visit New Orleans, I cannot live there.

When I arrive in a hotel I want a glass of ice water. In our two most recent visits to Marriott hotels in New Orleans, the ice machines on our floor did not at first work. It never worked during our stay at the first hotel and worked only occasionally at the second hotel. When I complained at the first hotel, I got a joyful grin and a shrug–the ice machine had been that way for several days and who knows when or if it would be fixed? It’s “easy” to celebrate; it’s hard to fix ice machines and keep them running.

There were barriers on Bourbon Street that could have kept the terrorist from killing 14. But it has come out that they were not working and it was not “easy” to fix them. (There were also supposed to be levies that could have reduced the damage from Hurricane Katrina, but it was not “easy” to fix them either.)

I like visiting New Orleans. I like its joyful spontaneity. But what makes New Orleans “the Big Easy” also makes it “the Big Frustrating” and “the Big Vulnerable.” I like visiting New Orleans but I want to live in a city where type-A personalities do what is hard: build, fix, and protect.

The Second Arthur Mansfield Diamond Would Be 100 Today

Dad holding me as a baby in 1953.
Dad holding me as a baby in 1953.

Happy Birthday Dad! He was the second Arthur Mansfield Diamond and would be 100 today.

I think if we adopt the right policies, many of us could live to 100. Too late for Dad, and almost certainly for me.

The first Arthur Mansfield Diamond died in 1933, I think. I was told he played the piano by ear and I saw an article saying that when he was a young man he briefly was a book-keeper for the family vaudeville activities. He looked dapper in a straw hat and knew Knute Rockne of Notre Dame. My Dad was eight when cancer took the first Arthur Mansfield Diamond. My Grandma, with no college degree, raised four children during the Great Depression. Cabbage was nutritious and cheap, so Grandma served a lot of sauerkraut. As an adult Dad hated sauerkraut.

Dad was always reading. He is the only person I ever met who read all three volumes of Solzhenitsyn’s Gulag Archipelago. And he read a conservative reader’s digest weekly (or monthly?) newspaper called Human Events. He was a Republican lawyer in an overwhelmingly Democratic county.

When my brothers and I were young he read aloud to us most of the Oz books, and other books including Atlas Shrugged. Thank you Dad, especially for that.

I wish I had finished my book before he died–he would have read it, argued with me about parts of it, but I think mostly liked it.

Dad was active in Toastmasters, a self-help organization for those who want to improve their public speaking. He rose to become the International President. Their headquarters is near Disneyland. When Dad first joined the Toastmasters board, he spent some time in the park. When he returned from that first trip, I remember his excitement at the then-new attraction, the Tiki Room–seeing what was possible in audio animatronics. Mom and Dad took us to Disneyland and on road trips to most of the U.S.

I remember Dad telling me in his last year that one of his regrets is that he won’t know how things turn out.

Dad was not perfect; neither am I. But I miss him and wish I could still talk with him, and thank him for his wit, his curiosity, and his courage in holding unpopular views when he thought they were right.

To End Drug Shortages Make Healthcare a Free Market

Drug shortages are sometimes blamed on the free market. A bum rap. In a free market when supply declines or demand increases, prices rise, and the increase in price incentivizes a greater quantity supplied, eventually ending a short-run period where quantity demanded at the going price exceeds quantity supplied at the going price (in other words, a shortage). But healthcare in America is far from a free market. Every aspect is highly regulated. Prices are negotiated, often by middlemen called (Pharmacy Benefit Managers, aka PBMs), entry is not free, and the demanders (patients) often do not know (or care) about the prices, since they are paid by a third party (insurers, employers, or the government). Perverse incentives abound.

(p. A26) There’s been a bombardment of bad news for drug supplies. The American Society of Health-System Pharmacists found this summer that nearly all of the members it surveyed were experiencing drug shortages, which generally affect half a million Americans. Cancer patients have scrambled as supplies of chemotherapy drugs dwindle. Other shortages include antibiotics for treatable diseases, such as the only drug recommended for use during pregnancy to prevent congenital syphilis (a disease that is 11 times more common today than a decade ago), and A.D.H.D. medications, without which people struggle to function in their day-to-day lives. The toll on Americans is heavy.

Over half of the shortages documented this summer by health consulting firm IQVIA had persisted for more than two years. But even though drug shortages affect millions of Americans, policymakers and industry leaders have provided little to no long-term relief for people in need.

Shortages have occurred regularly since at least the early 2000s, when national tracking began. Hundreds of drugs, in every major therapeutic category, have been unavailable for some period. The average drug shortage lasts about 1.5 years. Even when substitute medications are available, they may be suboptimal (for example, deaths by septic shock rose by 10 percent during a 2011 shortage of the first-line medication, norepinephrine) or have spillover effects (such as possibly increasing the risk of antimicrobial resistance). In addition to harming patients, shortages have cost health systems billions of dollars in increased labor and substitute medications.

. . .

Large hospital chains can readily monitor shortage risks and preemptively place large orders. This panic buying can wipe out inventory, and leave hospitals with fewer resources strapped since they may get notice of a drug shortage only when it’s too late. There is little penalty for over-ordering because unused drugs can often be returned.

. . .

Addressing the underlying fragility of our essential drug supply will take structural change and investments. While all industries must grapple with how to build resilient supply chains, the pharmaceutical industry is unique. The people who are most affected by supply chain vulnerabilities — patients — are also those with least say in the choice to buy from reliable manufacturers. When people buy cars, they may pay more based on company reputation, ratings by outside testers and reviews from other customers. In contrast, patients bear the harm of drug shortages, yet they cannot choose the manufacturers of their essential drugs nor evaluate their reliability.

For the full commentary see:

Emily Tucker. “We’re Stuck in a Constant Cycle of Drug Shortages.” The New York Times (Thursday, December 7, 2023 [sic]): A26.

(Note: ellipses added.)

(Note: the online version of the commentary has the date Dec. 6, 2023 [sic], and has the title “America Is Having Yet Another Drug Shortage. Here’s Why It Keeps Happening.”)

F.D.A. Should Allow Physicians and Parents the Freedom to Give Preterm Infants Probiotics

Substantial observational evidence shows that the status of a person’s microbiome can have a large effect on the person’s health. We still have a lot to learn about which bacteria are helpful and the details of how they help. But patients must act under uncertainty, or in the case of the preterm infants discussed in the passages quoted below, physicians and parents must act under uncertainty. Given the current evidence and the uncertainty, the F.D.A. is arrogantly wrong to ban probiotics.

(p. A5) For years, hospitals around the world have tried to protect prematurely born babies from life-threatening gut disease by giving them probiotics. Then . . . [in Oct. 2023], American hospitals stopped.

The Food and Drug Administration had linked an infant’s recent death to one of the products. It warned doctors about using them in preterm infants without getting agency permission first, and pushed Abbott Laboratories and another major manufacturer, Infinant Health, to stop selling them.

. . .

Neonatologists in the U.S. and other developed countries have learned to help smaller and smaller babies stay alive. As they treat tinier babies, the medical challenges mount, including a swift-onset disease known as necrotizing enterocolitis, or NEC.

. . .

To help prevent NEC, nearly all neonatal units in Australia and New Zealand give probiotics, as do a majority in several European countries. About 40% in the U.S. did before the FDA’s actions, according to recent surveys and neonatologists’ estimates.

Nearly all of the products consist of live bacteria intended to help create a healthy community of microbes in the gut. Scientists don’t know exactly how they work, but suspect they prevent harmful bacteria from overwhelming the bowels.

. . .

Neonatal units across the U.S. halted use of the probiotics because popular versions were no longer available and the FDA warned doctors against using probiotics for preterm babies outside of clinical trials.

“I was stunned,” said Jennifer Canvasser, who started a NEC patient advocacy group after her infant son died 10 years ago, weakened by the disease. “To think about families having one potential less way to prevent this devastating disease is just concerning.”

Probiotics supporters say the FDA disregarded the evidence favoring probiotics for preterm babies, saying that they likely save hundreds of infants for every one probiotic-caused infection, which can be treated with antibiotics.

An analysis of more than 100 studies involving more than 25,000 premature infants, published . . . [in Oct. 2023] in the journal JAMA Pediatrics, found that probiotics containing multiple strains of bacteria were associated with reduced deaths and NEC.

For the full story see:

Liz Essley Whyte. “Discord Arises Over Treating Preemie Babies.” The Wall Street Journal (Saturday, Nov. 17, 2023 [sic]): A5.

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

(Note: the online version of the story was updated Nov. 16, 2023 [sic], and has the title “Doctors, FDA Fight Over Giving Probiotics to Premature Babies.” The passages quoted above omit the subheadings that appear in the print, but not the online, version of the story.)

The analysis published in JAMA Pediatrics and mentioned above is:

Wang, Yuting, Ivan D. Florez, Rebecca L. Morgan, Farid Foroutan, Yaping Chang, Holly N. Crandon, Dena Zeraatkar, Malgorzata M. Bala, Randi Q. Mao, Brendan Tao, Shaneela Shahid, Xiaoqin Wang, Joseph Beyene, Martin Offringa, Philip M. Sherman, Enas El Gouhary, Gordon H. Guyatt, and Behnam Sadeghirad. “Probiotics, Prebiotics, Lactoferrin, and Combination Products for Prevention of Mortality and Morbidity in Preterm Infants: A Systematic Review and Network Meta-Analysis.” JAMA Pediatrics 177, no. 11 (2023): 1158-67.

For a useful discussion of how current medical protocols, especially the over-prescription of antibiotics, harm the microbiome, see chapter 3 of:

Makary, Marty. Blind Spots: When Medicine Gets It Wrong, and What It Means for Our Health. New York: Bloomsbury Publishing, 2024.

Health Insurance Firms Tell Regulators Surgery Prices Are Lower than What They Actually Charge, Undermining Price Transparency

Insurance firms that negotiate low prices with hospitals will be viewed more favorably by regulators, legislators, and the public. So they have a substantial incentive to inaccurately report prices as lower than they are. For true transparency, prices would need to be reported by those with no incentive to fudge the figures. Would that be hospitals, doctors, Consumer Reports, or academic economists?

(p. A11) How much does a new hip cost in New York? The answer isn’t at all clear, despite Gov. Andrew Cuomo’s efforts to improve price transparency.  . . .

. . . Michael Frank, a 52-year-old Westchester County executive . . . had his left hip replaced in 2015. The Manhattan hospital charged roughly $140,000. The insurance company paid a discounted rate of about $76,000, . . .

. . .

After hearing his story, I told Mr. Frank what I thought was an odd twist: I’d recently had two hips replaced, six months apart, at the same hospital that had treated him.

. . .

Eventually I learned that the hospital had charged $175,000 for my right hip and $180,000 for the left. The insurance company had paid discounted rates of $75,000 and $77,000.

. . .

In 2009, New York’s then-attorney general, Andrew Cuomo, announced the creation of a nonprofit organization called FAIR Health. Its mandate is to provide consumers accurate pricing information for all kinds of medical services.

I found the FAIR Health website and queried its database. It reported that the out-of-network price for a hip replacement in Manhattan was $72,656, close to what Mr. Frank’s and my insurance companies had paid. The problem: We were both in-network, and FAIR Health estimated that cost as only $29,162.

Something didn’t make sense, so I called FAIR Health. “Maybe you had complications,” the spokesperson suggested. Happily, I hadn’t. I was discharged from the hospital each time in under 24 hours, with no issues and no need for a home health aide. How many data points did FAIR Health use to calculate its price estimate? I was told “4,500 in Manhattan over the last six months.” Who submitted these prices? “The insurance companies.”

. . .  Rather than relying on insurers, it might be more effective if FAIR Health collected pricing information directly from hospitals and doctors. That way the data would be less susceptible to selective reporting or massaging. That’s what happened in the early 2000s, when class-action lawsuits revealed the main pricing database was being manipulated to the advantage of insurance companies.

For the full commentary see:

Steve Cohen. “You Can’t Put a Price on a Hip Replacement, and That’s a Problem.” The Wall Street Journal (Saturday, July 14, 2018 [sic]): A11.

(Note: ellipses added.)

(Note: the online version of the commentary has the date July 13, 2018 [sic], and has the title “Heard on the Street; New Biden Law Won’t Kill Drug Cures. It Will Reshape Them.” In the next to last paragraph quoted above, the second quoted sentence appears in the online, but not the print, version of the commentary.)

The American Academy of Pediatrics Ignored Early Evidence that Having Infants AVOID Peanuts CAUSES Peanut Allergy

I have praised Marty Makary’s Blind Spots in earlier posts, partly for its compelling examples of where mainstream medicine has failed to adapt to new, strong, sometimes observational evidence. His opening major example is the American Academy of Pediatrics’s long ban on giving peanuts to infants and toddlers. Instead of protecting them from peanut allergy, the ban caused a large increase in peanut allergy. In the essay quoted below, Makary summarizes the peanut example from Blind Spots.

(p. C4) In 1999, researchers at Mount Sinai Hospital estimated the incidence of peanut allergies in children to be 0.6%. But starting in the year 2000, the prevalence began to surge. Doctors began to notice that more children affected had severe allergies.

What had changed wasn’t peanuts but the advice doctors gave to parents about them. The American Academy of Pediatrics (AAP) wanted to respond to public concern by telling parents what they should do to protect their kids from peanut allergies. There was just one problem: Doctors didn’t actually know what precautions, if any, parents should take. Rather than admit that, in the year 2000 the AAP issued a recommendation for children 0 to 3 years old and pregnant and lactating mothers to avoid all peanuts.

. . .

Dr. Gideon Lack, a pediatric allergist and immunologist in London, had a different view. In 2000 he was giving a lecture in Israel on allergies and asked the roughly 200 pediatricians in the audience, “How many of you are seeing kids with a peanut allergy?” Only two or three raised their hands. Back in London, nearly every pediatrician had raised their hand to the same question.

Startled by the discrepancy, he had a eureka moment. Many Israeli infants are fed a peanut-based food called Bamba. To Lack, this was no coincidence, and he quickly assembled researchers in Tel Aviv and Jerusalem to launch a formal study. It found that Jewish children in Israel had one-tenth the rate of peanut allergies compared with Jewish children in the U.K., suggesting that genetic predisposition was not responsible, as the medical establishment had assumed.

Lack and his Israeli colleagues titled their paper “Early Consumption of Peanuts in Infancy Is Associated with a Low Prevalence of Peanut Allergy.” However, the 2008 publication was not enough to uproot groupthink. Avoiding peanuts had been the correct answer on medical school tests and board exams, which were written and administered by the American Board of Pediatrics. For nearly a decade after AAP’s peanut avoidance recommendation, neither the National Institute of Allergy and Infectious Diseases (NIAID) nor other institutions would fund a robust study to evaluate whether the policy was helping or hurting children.

Meanwhile, the more that health officials implored parents to follow the recommendation, the worse peanut allergies got. From 2005 to 2014, the number of children going to the emergency department because of peanut allergies tripled in the U.S. By 2019, a report estimated that 1 in every 18 American children had a peanut allergy.  . . .

In a second clinical trial, published in the New England Journal of Medicine in 2015, Lack compared one group of infants who were exposed to peanut butter at 4-11 months of age to another group that had no peanut exposure. He found that early exposure resulted in an 86% reduction in peanut allergies by the time the child reached age 5 compared with children who followed the AAP recommendation.

. . .

When modern medicine issues recommendations based on good scientific studies, it shines. Conversely, when doctors rule by opinion and edict, we have an embarrassing track record. Unfortunately, medical dogma may be more prevalent today than in the past because intolerance for different opinions is on the rise, in medicine as throughout society.

For the full essay see:

Marty Makary. “Who’s Responsible for America’s Peanut Allergy Epidemic?” The Wall Street Journal (Saturday, Sept. 21, 2024): C4.

(Note: the online version of the essay has the date September 19, 2024, and has the title “How Pediatricians Created the Peanut Allergy Epidemic.”)

Makary’s essay is adapted from his book:

Makary, Marty. Blind Spots: When Medicine Gets It Wrong, and What It Means for Our Health. New York: Bloomsbury Publishing, 2024.

The So-Called “Inflation Reduction Act” Reduces Incentives to Develop Small Molecule Drugs and Drugs for Seniors

A recent blog entry suggested that the so-called “Inflation Reduction Act” “creates an incentive for Pharma firms to develop many middling drugs rather than a couple of blockbuster drugs.” In the passages quoted below from a different David Wainer commentary, he suggests that the Act also incentivizes pharma firms to reallocate development funds away from drugs for seniors and away from biologics. He assumes that the reallocation is “unintended” rather than based on the government believing that seniors matter less than others, or that biologics deserve more funding than the previous semi-free market allocated to biologics.

(p. B14) . . . the Inflation Reduction Act, . . . requires the federal government to negotiate prices for some drugs. Merck Chief Executive Officer Robert Davis was just one of many to warn it will be “highly chilling on future innovation.”

The 274-page legislation passed in 2022 doesn’t look likely to be a massive damper on innovation, but it will surely have an impact on how capital is allocated. When companies look at their R&D budgets, they will have to consider the law’s ramifications.

. . .

. . ., there is no arguing with the fact that the bill is reshaping many incentives drug companies face. For example, critics of the law point out that it eliminates the incentive to conduct additional research once a drug has been approved—a common strategy to extend patent protection for a drug—because prices are negotiated after nine years for small-molecule drugs and 13 years for biologics. As Kirsten Axelsen, a visiting scholar at the American Enterprise Institute explains, many oncology medications are first approved for severely ill patients and over time those drugs are tested for patients in earlier stages of the disease.

“Thanks to that, we’re now able to hold back the progression of cancer so that many of the major cancers have five-year survival rates of longer than 90%,” says Ms. Axelsen, who is also a policy adviser to law firm DLA Piper.

. . .

The law . . . could shift investment toward drugs that target the general population and away from seniors. That is because it only empowers Medicare to negotiate prices, leaving the commercial market wide open.

. . .

Perhaps the most serious concern is that the law picks winners and losers by favoring biologic drugs over small molecules, which face price reductions four years sooner than their larger molecule counterparts.

Small molecule drugs are chemically derived and simpler to make and can usually be taken orally by patients. These drugs—think medicine cabinet essentials like aspirin or statins—dominated the pharmaceutical industry during the 20th century. Biologics, therapies that are extracted from living organisms, are usually given through an injection and, because of their higher price tags, make up the bulk of today’s top-selling drugs. While biologics are at the cutting edge of medicine, discoveries of new small-molecule drugs continue to be made.

Eli Lilly’s CEO, David Ricks, noted in a recent earnings call that “it sends a signal to investors” that small molecules “aren’t wanted and are worth a lot less.” That could tip the scales toward more development in biologics, a likely unintended consequence of the law.

MIT’s Professor Lo says that is like effectively creating a tax on small molecules, or a subsidy for larger ones.

For the full commentary see:

Wainer, David. “Heard on the Street; Drug Industry’s Secret Weapon: ‘Guided Missiles’.” The Wall Street Journal (Saturday, Jan. 7, 2023 [sic]): B14.

(Note: ellipses added.)

(Note: the online version of the commentary has the date January 6, 2023 [sic], and has the title “Heard on the Street; New Biden Law Won’t Kill Drug Cures. It Will Reshape Them.” In the next to last paragraph quoted above, the second quoted sentence appears in the online, but not the print, version of the commentary.)

Regulators Wanted to Renege on Promise to Clinical Trial Volunteers Who Got the Placebo

Everyone agrees that those who receive the placebo in a randomized double-blind controlled trial (RCT) are losers in the clinical lottery. The question is whether the epistemic gain from RCTs justifies the pain for the losers? I am not a fan of Fauci, but his proposed solution to the dilemma in the case discussed below seems plausible, if we assume (as I do not) that RCTs are a necessary condition for all actionable medical knowledge and yet we still attempt to treat clinical trial volunteers ethically. My even better solution is to allow all willing volunteers to take the experimental drug, with no-one receiving a placebo. Then use some Bayesian updating technique to gather information from the comparison of results for study participants who volunteered to take the drug, with results for study participants who did not volunteer to take the drug. The study would not be blind, but useful information could be obtained, for instance if no one who takes the drug suffers from the disease, but many who do not take the drug, do suffer from the disease. In that case we have evidence that the drug is effective.

(p. A7) In October [2020], Judith Munz and her husband, Scott Petersen, volunteered for a coronavirus vaccine trial. At a clinic near their home in Phoenix, each got a jab in the arm.

Dr. Petersen, a retired physician, became a little fatigued after his shot, and developed redness and swelling on his arm. But Ms. Munz, a social worker, didn’t notice any change. “As much as I wanted it, I couldn’t find a darned thing,” she said. “It was a nothing burger.”

She knew there was a 50-50 chance that she would get the vaccine, developed by Johnson & Johnson. Judging from her lack of symptoms, she guessed she had received the placebo.

At the time, Ms. Munz thought that anyone who had received the placebo would get the real vaccine as soon as the trial showed it was safe and effective. She looked forward to the peace of mind it would bring. But last month, she was asked to sign a modified consent form indicating that people who got the placebo might have to wait up to two years to get the vaccine, if they got one at all.

Ms. Munz found the form vague, confusing and, most of all, unfair. “You put yourself out there with that risk,” she said. “I am owed that vaccine.”

. . .

But on Wednesday [Dec. 2, 2020], 18 leading vaccine experts — including a top regulator at the Food and Drug Administration — argued that vaccinating placebo groups early would be disastrous for the integrity of the trials. If all of the volunteers who received placebo shots were to suddenly get vaccinated, scientists would no longer be able to compare the health of those who were vaccinated with those who were not.

“If you’re going to prioritize people to get vaccinated, the last people you should vaccinate are those who were in a placebo group in a trial,” said Richard Peto, a medical statistician at the University of Oxford. Mr. Peto and his colleagues laid out their concerns in a new commentary in The New England Journal of Medicine.

. . .

Yet the prospect of giving people something useless in the face of a life-threatening disease has always been fraught. Even Jonas Salk balked at the idea of giving people placebos when researchers designed a trial to test his new polio vaccine in 1953.

“I would feel that every child who is injected with a placebo and becomes paralyzed will do so at my hands,” he complained. The study, Dr. Salk declared, “would make Hippocrates turn over in his grave.”

. . .

Dr. Fauci sketched out one possible way to balance the obligation owed to people who took the placebo against the need for more data from the trials. Vaccine makers could give everyone who got the placebo the vaccine — while also giving everyone who got the vaccine the placebo. None of the trial participants would know which order they got the doses. The trial could therefore continue to be blinded.

. . .

After learning that it may take two years before Johnson & Johnson will provide her with the real vaccine, Ms. Munz, who is 68, is considering trying to get Pfizer or Moderna’s version as soon as she’s eligible thanks to her age.

“I’ll drop out, which I can do, and I’ll get the vaccine,” she said.

Holly Janes, a biostatistician at the Fred Hutchinson Cancer Research Center in Seattle, and her colleagues are preparing for this kind of erosion. She and her colleagues are now working on statistical methods to squeeze the most insight out of the trials no matter what their fate.

“It won’t be ideal from a purely scientific vantage point, because we lose the direct comparison between vaccine and placebo,” she said. “But we’re trying to strike a balance between doing what some would argue is right for the participants, and maximizing the public health value that comes out of these trials.”

For the full story see:

Carl Zimmer and Noah Weiland. “Should Volunteers Who Got Placebo Be First to Get the Real Thing?” The New York Times (Thursday, December 3, 2020): A7.

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

(Note: the online version of the story was updated Dec. 18, 2020 [sic], and has the title “Many Trial Volunteers Got Placebo Vaccines. Do They Now Deserve the Real Ones?”)

Regulations Discourage Search for Magic Bullet Cures

The so-called “Inflation Reduction Act” mandates that several of the biggest blockbuster drugs must have prices negotiated between Medicare and Pharma firms. As the commentary quoted below suggests, this creates an incentive for Pharma firms to develop many middling drugs rather than a couple of blockbuster drugs. Paul Ehrlich’s “magic bullet” may be impossible, but we will never know if no-one is trying to discover it.creates an

(p. B10) A true home run in the drug industry is when a company develops a mega-blockbuster that transforms its finances for years.

But with Medicare trying to bring costs down by targeting the industry’s most expensive drugs, a portfolio of medium-size moneymakers that can keep your name off the U.S. government’s naughty list can be a wise strategy.

That is at least one reason why big pharma is investing heavily in biotech companies developing antibody-drug conjugates. Known as ADCs, these treatments work like a guided missile by pairing antibodies with toxic agents to fight cancer. In short, they enable a more targeted form of chemotherapy that goes straight into the cancer cells while minimizing harm to healthy cells.

. . .

One reason most ADCs aren’t likely to become mega-blockbusters like Keytruda, a cancer immunotherapy that has earned 35 approvals across 16 types of cancer, is that they aren’t one-size-fits-all drugs. Instead, they are designed to target a specific protein that is expressed on the surface of a cancer cell. That means that each drug is made with an antibody targeting a subset of cancer. There are more than 100 ADCs being tested in humans by pharma and biotech companies.

For the full commentary see:

David Wainer. “Heard on the Street; Drug Industry’s Secret Weapon: ‘Guided Missiles’.” The Wall Street Journal (Friday, Oct. 27, 2023 [sic]): B10.

(Note: ellipsis added.)

(Note: the online version of the commentary has the date October 26, 2023 [sic], and has the title “Heard on the Street; ‘Guided Missile Drugs’ Could Be Big Pharma’s Secret Weapon.”)