Category: Regulations

When the Highly Restrictive Enrollment Criteria for Clinical Trials Steal Hope from the Innocently Desperate, It “Just Feels Unjust”

Muscular dystrophy is sometimes called “Duchenne.” The full name of the disease is “Duchenne muscular dystrophy.” When I was a student at Monroe elementary school a classmate named Frank Goldsberry played on the basketball team. In high school he was in a wheel chair with muscular dystrophy. When the high school principle, Howard Crouch, proposed to do away with the academic honor of valedictorian on the ground that there was some arbitrariness in who received it, I argued that to do would be to diminish the honor given to academic achievement. Crouch relented. It turned out that our valedictorian was Frank Goldsberry. He died a few years later in his early 20s. Frank’s father told my mother that Frank was grateful to me for speaking up. Howard Crouch had a point, but I am glad that after working hard under dire circumstances, Frank received the award.

The F.D.A. should stop mandating randomized double-blind clinical trials (RCTs) so that those who have muscular dystrophy can seek any therapy that they, their parents, and their physicians believe has promise. Not everyone will be cured, but we will learn what works through a Bayesian process of trial and error. More parents and boys will be allowed to hold on to hope.

(p. D1) Lucas was 5 before his parents, Bill and Marci Barton of Grand Haven, Mich., finally got an explanation for his difficulties standing up or climbing stairs. The diagnosis: muscular dystrophy.

Mr. Barton turned to Google.

“The first thing I read was, ‘no cure, in a wheelchair in their teens, pass in their 20s,” Mr. Barton said. “I stopped. I couldn’t read any more. I couldn’t handle it.”

Then he found a reason to hope. For the first time ever, there are clinical trials — nearly two dozen — testing treatments that might actually stop the disease.

The problem, as Mr. Barton soon discovered, is that the enrollment criteria are so restrictive that very few children qualify. As a result, families like the Bartons often are turned away.

. . .

Ryan and Brooke Saalman know how hard it can be to know what to do. “We did a lot of praying,” said Ms. Saalman, mother of two boys with Duchenne in Columbus, Ga.

They decided to enroll their oldest son, Jacob, 6, in a trial of a highly experimental drug.

. . .

. . . they discovered that gene therapy may be irreversible. And if it didn’t work, Ja-(p. D3)cob would be ineligible for an even more promising approach in the future: gene editing, to snip out the deadly mutation that causes Duchenne, an effort now in preclinical development.

. . .

The Bartons found out about a gene-therapy trial at Nationwide Children’s Hospital in Columbus, Ohio, testing a treatment by Sarepta Therapeutics.

They watched a miraculous video of a little boy struggling to walk up a flight of stairs before treatment — and then doing it easily afterward.

“This was what we were hoping for,” Mr. Barton said.

Lucas was the right age, and he seemed to qualify. But testing showed that he carries antibodies to the virus used to deliver the treatment. It would not work for him.

The Bartons were drained, devastated. And for now, there is no other trial that Lucas qualifies for.

“I had my put my hopes into this,” Mr. Barton said. “It was the miracle.”

Dr. Jeffrey Bigelow, a neurologist, and his wife, Alexis Bigelow, of Millcreek, Utah, hoped against hope that their son Henri, 8, would qualify for the only gene therapy trial that will accept boys his age.

Then the Bigelows found out that enrollees of Henri’s age have to be able to lie down and then stand up with their hands at their sides in less than 10 seconds.

It took Henri 10 seconds to do that last spring, when he was evaluated for another trial. Now it would probably take him 20 seconds, his father said.

“It feels like Henri is being punished for losing the ability to stand up from the ground too soon,” Dr. Bigelow said.

He also worries about older boys with Duchenne who are lucky enough to still walk. They are shut out from the trial because they are not yet in wheelchairs. And other trials won’t accept boys that old.

“These are boys who, like Henri, desperately need the treatment, and if they don’t get it in the next one to two years, likely will be confined to a wheelchair, to never walk again,” Dr. Bigelow said.

“This just feels unjust.”

For the full story see:

Gina Kolata. “One Shot To Qualify For Hope.” The New York Times (Tuesday, March 26, 2019 [sic]): D1 & D3.

(Note: ellipses added.)

(Note: the online version of the story has the date March 25, 2019 [sic], and has the title “For Many Boys With Duchenne Muscular Dystrophy, Bright Hope Lies Just Beyond Reach.”)

Rigid Guidelines Don’t Allow for Individualizing Treatment and Discount the Doctor’s Clinical Judgment

The criticism of the Clovers sepsis clinical trial is that the the treatment and placebo arms of the trial each require rigid adherence to a protocol, and such adherence rules out personalizing individual treatment based on individual differences among patients and doctors’ clinical judgment based on past experiences. That criticism seems plausible and also seems to apply, not just to the Clovers sepsis clinical trial, but to all< randomized double-blind clinical trials.

(p. D1) A large government trial comparing treatments for a life-threatening condition called sepsis is putting participants at risk of organ failure and even death, critics charge, and should be immediately shut down.

A detailed analysis of the trial design prepared by senior investigators at the National Institutes of Health Clinical Center in Bethesda, Md., concluded that the study “places seriously ill patients at risk without the possibility of gaining information that can provide benefits either to the subjects or to future patients.”

In a letter to the federal Office for Human Research Protection, representatives of Public Citizen’s Health Research Group compared the study, called Clovers, to “an experiment that would be conducted on laboratory animals.”

“The human subjects of the Clovers trial, as designed and currently conducted, are unwitting guinea pigs in a physiology experiment,” Dr. Michael Carome and Dr. Sidney M. Wolfe wrote in their letter.

Begun in March, Clovers is funded by the N.I.H. — despite the criticism of its own investigators — and aims to enroll 2,320 pa-(p. D3)tients at 44 hospitals around the country.

. . .

At issue is whether patients participating in Clovers are being given treatment that deviates from usual care — so much so that lives may be endangered by the research.  . . .

When patients experience septic shock, current guidelines call for raising blood pressure by administering fluids within the first three hours of care, and then administering vasopressors within the first six hours if patients do not respond to fluids.

Vasopressors can be administered early on, during or after the infusion of fluids; a new treatment guideline for hospitals says the drugs should be started within the first hour if patients aren’t responding to intravenous fluids.

Many physicians have been critical of rigid guidelines like this one because they don’t allow for individualizing treatment and appear to discount the doctor’s clinical judgment.

Both fluids in large amounts and vasopressors can cause serious complications, but when a patient’s condition continues to deteriorate, doctors use both interventions, adjusting them depending on the severity of illness.

They generally start with fluids, which in small amounts are considered less toxic than vasopressors.

But participants in Clovers are randomly assigned to a “liberal fluids” group who receive large infusions of fluids in a very short time but limits the use of vasopressors, or to a “restrictive fluids” group in which fluids are minimized and drug treatment begun earlier.

For the full story see:

Roni Caryn Rabin. “Critics Demand Halt of a Sepsis Trial.” The New York Times (Tuesday, September 25, 2018 [sic]): D1 & D3.

(Note: ellipses added.)

(Note: the online version of the story has the date Sept. 24, 2018 [sic], and has the title “Trial by Fire: Critics Demand That a Huge Sepsis Study Be Stopped.”)

The Number of Alzheimer’s Patients Is Too Few to Populate the Many Promising Clinical Trials

When the F.D.A. mandates randomized double-blind clinical trials (RCTs) be successfully performed before allowing the use of a new drug, it also mandates that diverse promising drugs will never be tested. Some of those drugs might help or even cure Alzheimer’s. The reason that some diverse promising drugs will never be tested, as explained by Gina Kolata in the passage quoted below, is that there are too few diagnosed and willing Alzheimer’s patients to conduct the number and kind of RCTs that the government mandates, for all the promising drugs under development. What is the alternative to mandated RCTs? Allow physicians to prescribe drugs that have a promising rationale. If their patients benefit the physicians will continue to prescribe the drug and they will tell their colleagues.

(p. D1) The task facing Eli Lilly, the giant pharmaceutical company, sounds simple enough: Find 375 people with early Alzheimer’s disease for a bold new clinical trial aiming to slow or stop memory loss.

There are 5.4 million Alzheimer’s patients in the United States. You’d think it would be easy to find that many participants for a trial like this one.

But it’s not. And the problem has enormous implications for treatment of a disease that terrifies older Americans and has strained families in numbers too great to count.

The Global Alzheimer’s Platform Foundation, which is helping recruit participants for the Lilly trial, estimates that to begin finding participants, it will have to inform 15,000 to 18,000 people in the right age groups about the effort.

Of these, nearly 2,000 must pass the initial screening to be selected for further tests to see if they qualify.

Just 20 percent will meet the criteria to enroll in Lilly’s trial: They must be aged 60 to 89, have mild but progressive memory loss for at least six months, and have two types of brain scans showing Alzheimer’s is underway.

Yet an 80 percent screening failure rate is typical for Alzheimer’s trials, said John Dwyer, president of the foundation. There is just no good way to quickly diagnose the disease.

The onerous process of locating just 375 patients illustrates a grim truth: finding patients on whom to test new Alzheimer’s treatments is becoming an insurmountable obstacle — no matter how promising the trial.

With brain scans, lab tests and memory tests, the cost per diagnosis alone is daunting — as much as $100,000 for each person who ends up enrolled in a trial, Mr. Dwyer said — even before they begin the experimental treatment.

Complicating the problem, the number of trials has exploded in recent years. There (p. D4) are more than 100 Alzheimer’s studies looking for a whopping 25,000 participants, Mr. Dwyer said.

To begin filling them all, 37.5 million patients in the right age group would first have to be informed. Ten percent would be referred to a trial site for screening.

Just 4 percent will move forward with an evaluation, and of these, just over 17 percent will drop out, given the current rate, leaving roughly 125,000 to be screened. And with an 80 percent screening failure rate, that leaves 25,000 participants of the 37.5 million who were first informed.

The numbers make it clear: There’s no way scientists are going to find 25,000 participants for all of the Alzheimer’s trials that have been approved.

“The irony is that the science has never been more promising,” Mr. Dwyer said. “How many promising drugs will be abandoned or their evaluation seriously delayed? Some good science is going to be left on cutting-room floor.”

For the full story see:

Gina Kolata. “Alzheimer’s Trials Hit a Roadblock.” The New York Times (Tuesday, July 24, 2018 [sic]): D1 & D4.

(Note: the online version of the story has the date July 23, 2018 [sic], and has the title “For Scientists Racing to Cure Alzheimer’s, the Math Is Getting Ugly.”)

F.D.A. Chief Sets Low Bar for Cancer Progress–Three Months of Longer Life Is “A Major Therapeutic Advance”

F.D.A. regulations have slowed progress toward curing cancer. Rather than reduce regulations, the head of the F.D.A. redefines “progress” as occurring when a new drug increases average lifespan by a mere three months.

(p. D3) Was there a moment when you realized a new era had begun?

It was a gradual thing. I wish I could say I had an “a-ha” moment.

I remember though, one of our first approvals of a PD-1 drug (a drug that unleashes the immune system to fight cancer). A division director sent me an email with a survival curve for patients in a study. It was a Friday afternoon. I saw it and I nearly fell off my seat. It was such a positive study for these patients with squamous cell lung cancer. They lived an average of six months with standard chemotherapy. With the new drug they lived 9.2 months.

I called the division director and said, “What are we going to do to expedite this?”

We had to get a submission from the drug company and that can take several months. Sometimes it takes six months and sometimes up to a year because of the voluminous amount of material that must be provided.

We got the submission in a couple of months. Nivolumab was approved in March of 2015.

It was a major therapeutic advance. These were people who heretofore had few therapeutic options.

. . .

. . ., my regret? I won’t be here in 2049, my presumed 50th F.D.A. anniversary.

I would love to see what oncology looks like given the rapid changes in the past 25 years. Hang on tight. The velocity of innovation will only increase.

For the full interview see:

Gina Kolata, interviewer. “F.D.A.’s Cancer Chief Is Forward Focused.” The New York Times (Tuesday, November 19, 2024): D3.

(Note: ellipses added.)

(Note: the online version of the interview has the date Nov. 8, 2024, and has the title “He’s the F.D.A.’s Cancer Chief, Not a Fortune Teller.” The question is from the interviewer Gina Kolata. The rest of the words are quoted from the answers of Dr. Richard Pazdur.)

Peppermint at One Time Required a Prescription, While Strychnine Was Sold Over-the-Counter

I suspect I would not much like the Remaking the American Patient book–it seems to blame capitalism for all of the ills of the healthcare system. But it does include one compelling example of the limitations of government regulation of drugs: allowing strychnine while restricting peppermint.

(p. D3) Medical historians who focus on the conquest of dire diseases serve up narratives of progress and triumph. Not Ms. Tomes, a professor of history at Stony Brook University, who has chosen to examine instead the health care experience of average healthy citizens, the great silent majority whose lives are punctuated by a variety of minor ills and only the occasional major calamity.

. . .

Are you perplexed by our regulatory chaos, with layer upon layer of well-meaning but persistently ineffective efforts to guarantee the safety of medical services? It turns out we come from a long tradition of such inadequacy: Patient safety has been the holy grail for everyone, long sought, never achieved.

Drug regulatory efforts have been inconsistent and confusing. (At one point in the 1940s, peppermint drops were available by prescription, while strychnine could be freely purchased by anyone).

For the full review see:

Abigail Zuger, M.D. “When Patients Became Purchasers.” The New York Times (Tuesday, January 26, 2016 [sic]): D3.

(Note: ellipsis added.)

(Note: the online version of the review has the date Jan. 23, 2016 [sic], and has the title “Review: ‘Remaking the American Patient’.”)

The book under review above is:

Tomes, Nancy. Remaking the American Patient: How Madison Avenue and Modern Medicine Turned Patients into Consumers, Studies in Social Medicine. Chapel Hill: The University of North Carolina Press, 2016.

Democratic New York Department of Environmental Conservation Raids Home, Seizing and Killing P’Nut, Internet-Famous Orphan Pet Squirrel

(p. A15) . . . P’Nut was an internet-famous squirrel who was seized and euthanized by New York State wildlife agents last week . . .

. . .

. . . Elon Musk lionized the rodent as a Jedi martyr — more powerful in death than in life.

“RIP Peanut,” read a post on a Trump campaign’s official TikTok account on Sunday [Nov. 3, 2024]. “Needlessly murdered by Democrat bureaucrats in New York.”

. . .

P’Nut’s journey from cowboy-hat-wearing Instagram cutie to conservative lightning rod began on Oct. 30 [2024]. That was when New York State Department of Environmental Conservation officers, responding to what the agency said were anonymous complaints, arrived at the home of his owner, Mark Longo, in Pine City in Chemung County. In New York State, it is illegal to house animals considered wildlife without a special permit; Mr. Longo has said he was in the process of applying for one.

D.E.C. agents seized the squirrel, which Mr. Longo had cared for ever since its mother was hit by a car seven years ago. Agents also apprehended Fred the raccoon. At some point, the squirrel bit a person involved with the investigation, according to a statement put out by the agency, leading its officers to swiftly euthanize both animals to test for rabies.

In tearful online posts, Mr. Longo and his wife, Daniela, railed against tax dollars being spent to kill the animals they considered pets.

. . .

In Macon, Ga., Marjorie Taylor Greene, the Georgia congresswoman, spoke at a Trump rally and compared Peanut’s fate to that of Laken Riley, a local woman who was killed by a Venezuelan man who had once lived in New York. She blamed Democrats in New York City, which is 200 miles from Pine City, for euthanizing P’Nut.

“Democrats in New York City went in and raided a home to kill a squirrel,” Ms. Greene said. “Yet it was the same State of New York that let the criminal illegal alien go that came to Georgia that murdered our very own Laken Riley.”

. . .

. . . the animals’ owner, Mr. Longo, 34, considers himself apolitical. He is not registered with any political party and said he has never voted in his life.

. . .

He has spent the past days grieving, he said, and when he found a stray almond that Peanut had sneaked into his pocket, he burst into tears. He was just grateful, he said, “that somebody is giving P’Nut a voice.”

“I don’t care if it was the blue side or the red side,” he added. “Somebody on this planet is fighting for my animals.”

For the full story see:

Sarah Maslin Nir. “Death of a Pet Squirrel Is a G.O.P. Rallying Cry.” The New York Times (Wednesday, November 6, 2024): A15.

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

(Note: the online version of the story has the date Nov. 4, 2024, and has the title “How the Death of a Celebrity Squirrel Became a Republican Rallying Cry.”)

Universally Applicable Egg Guidelines Are Impossible Because Some Are Hypo-Responders and Others Are Hyper-Responders to Dietary Cholesterol

(p. D5) “Intervention studies have shown that moderate egg consumption doesn’t appreciably raise cholesterol levels,” Dr. Hu [chairman of nutrition and epidemiology at the Harvard T.H. Chan School of Public Health] said. “Low to moderate consumption of three or four eggs a week doesn’t appear to have a major effect on blood cholesterol unless the person has high cholesterol or Type 2 diabetes.”

He added, “In most previous studies of healthy people, moderate egg consumption was not associated with a significant increase in cardiovascular risk.” However, among 21,275 participants in the Physicians’ Health Study who were followed for more than 20 years, those who ate one or more eggs a day were more likely to develop heart failure than those who ate eggs infrequently.

“Contradictory findings among different studies are not unusual — it’s part of the scientific process,” Dr. Hu said. “In forming guidelines, you have to look at the totality of evidence rather than overreact to a single new study.”

Zachary S. Clayton, author of a comprehensive review of research on egg consumption and heart health published in Nutrition in 2017, said in an interview that giving two eggs a day for 12 weeks to healthy people didn’t raise any of their cardiovascular risk factors and “actually decreased their triglyceride levels.”

But, Dr. Clayton, a postdoctoral fellow in nutrition at the University of Colorado, Boulder, said, “It’s important to distinguish between hypo-responders and hyper-responders to dietary cholesterol. If someone is a hyper-responder, eating two eggs a day would increase the risk of cardiovascular disease.”

For the full commentary see:

Jane E. Brody. “Cracking the Code on Eggs and Your Diet.” The New York Times (Tuesday, April 23, 2019 [sic]): D5.

(Note: bracketed words quoted from earlier in the commentary.)

(Note: the online version of the commentary has the date April 22, 2019 [sic], and has the title “Should You Be Eating Eggs?”)

Clayton’s co-authored academic review article on the effects of egg consumption, mentioned above, is:

Clayton, Zachary S., Elizabeth Fusco, and Mark Kern. “Egg Consumption and Heart Health: A Review.” Nutrition 37 (May 2017): 79-85.

A Drug’s Lack of Randomized Clinical Trials Does Not Imply the Drug Lacks Efficacy

(p. D5) In 2013, the American College of Cardiology and the American Heart Association issued a series of statin recommendations for primary prevention, relevant to adults up to age 75 who have high cholesterol or diabetes, or who for other reasons face an estimated 7.5 percent risk or greater of developing heart disease within 10 years.

Last year, the United States Preventive Services Task Force similarly recommended statins for primary prevention in people aged 40 to 75 who had risk factors like high cholesterol, diabetes, high blood pressure or smoking, with a 10-year disease risk of 10 percent or greater.

But for people over age 75, both panels agreed, there was not sufficient evidence to reach a conclusion. As with many clinical trials, the major statin studies mostly haven’t included patients at advanced ages.

. . .

But Dr. Paul Ridker, a self-described “statin advocate” who directs the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital in Boston, gets irked at the argument that we don’t know enough to give statins to older patients without heart disease.

“I don’t believe there’s any doubt that statin therapy is effective for primary prevention in older adults,” Dr. Ridker said. He cites a recent reanalysis of data from two major studies showing that patients over age 70 taking statins experienced the same reductions in cardiovascular events and mortality as younger ones.

Dr. Orkaby and her Harvard colleagues hoped to help resolve such questions with their recent study, published in the Journal of the American Geriatrics Society, comparing physicians over age 70 who took statins for primary prevention with those who didn’t.

The team matched each group for 30 variables and found that over an average of seven years, statin-takers had an 18 percent lower death rate, though not a statistically significant reduction in cardiovascular events.

In the same issue, though, an editorial co-authored by Dr. Rich called statin use for primary prevention in older patients “an unresolved conundrum.”

The physician study was observational, so can’t establish causes, he pointed out.

For the full story see:

Paula Span. “The New Old Age; If You’re Over 75 and Healthy, Are Statins for You?” The New York Times (Tuesday, January 9, 2018 [sic]): D5.

(Note: ellipsis added.)

(Note: the online version of the story has the date January 5, 2018 [sic], and has the title “The New Old Age; You’re Over 75, and You’re Healthy. Why Are You Taking a Statin?”)

The article on the effect of statins on older physicians, co-authored by Orkaby and mentioned above, is:

Orkaby, Ariela R., J. Michael Gaziano, Luc Djousse, and Jane A. Driver. “Statins for Primary Prevention of Cardiovascular Events and Mortality in Older Men.” Journal of the American Geriatrics Society 65, no. 11 (Nov. 2017): 2362-68.

Government Sugar Quotas Increase Demand for Harder-to-Metabolize Corn Syrup, Making Americans Fatter

For decades on the last day of every micro principles class I discussed the causes and effects of U.S. government sugar quotas. Government sugar quotas reduce the quantity of sugar that can be imported into the U.S., increasing the price of sugar. If the price of one substitute (sugar) rises, the demand for the other substitute (corn syrup) increases. As a result Americans consume more corn syrup which is harder to metabolize and easier to overconsume. Government sugar quota regulation thus increases obesity, and obesity-related diseases such as diabetes, heart disease, and cancer.

(p. D5) To clarify the effects of our high-sugar diet, I consulted an expert, Kimber L. Stanhope, a researcher in nutritional biology at the University of California, Davis, whose work is free of industry support and funded primarily by the National Institutes of Health. In a comprehensive 34-page review of research published in Critical Reviews in Clinical Laboratory Sciences in 2016, she linked consumption of added sugar to metabolic disease — cardiovascular disease, Type 2 diabetes and nonalcoholic fatty liver disease — as well as high blood levels of uric acid, a risk factor for kidney stones and gout.

In studies done in her lab among young adults consuming their normal diets, the risk for developing heart disease and kidney stones rose in direct proportion to the amount of high-fructose corn syrup they consumed.

. . .

“Fructose and glucose are not metabolized the same way in the human body,” which can account for the adverse effects of fructose, Dr. Stanhope said. Glucose is metabolized in cells throughout the body and used for energy. Fructose is metabolized in the liver, resulting in fat production and raising the risk of heart and fatty-liver disease. In addition, she explained, “fructose doesn’t stimulate the satiety-promoting substance leptin,” prompting some people to overconsume it, especially in soft drinks containing high-fructose corn syrup, and other tempting foods as well.

For the full story see:

Jane E. Brody. “The Sharp Bite of a Sweet Tooth.” The New York Times (Tuesday, July 23, 2019 [sic]): D5.

(Note: ellipsis added.)

(Note: the online version of the story has the date July 22, 2019 [sic], and has the title “The Downside of Having a Sweet Tooth.”)

The review article on the effect of sugar consumption on metabolism and obesity, mentioned above, is:

Stanhope, Kimber L. “Sugar Consumption, Metabolic Disease and Obesity: The State of the Controversy.” Critical Reviews in Clinical Laboratory Sciences 53, no. 1 (2016): 52-67.

Constraints and Incentives Help Explain Useless Medical Procedures

(p. D4) Researchers surveyed 2,106 physicians in various specialties regarding their beliefs about unnecessary medical care. On average, the doctors believed that 20.6 percent of all medical care was unnecessary, including 22 percent of prescriptions, 24.9 percent of tests and 11.1 percent of procedures. The study is in PLOS One.

Nearly 85 percent said the reason for overtreatment was fear of malpractice suits, . . .

. . .

More than 70 percent of doctors conceded that physicians are more likely to perform unnecessary procedures when they profit from them, while only 9.2 percent said that their own financial security was a factor.

“This study is essentially the voice of physicians about the problem,” said the senior author, Dr. Martin A. Makary, a professor of surgery at Johns Hopkins. “We’re told that there are too many operations done for narrowed blood vessels in the legs. Spine surgeons say that a quarter of all spine surgery may not be necessary. Half of stents placed may be unnecessary. These are significant opportunities to improve quality and lower costs.”

For the full story see:

Nicholas Bakalar. “Doctors: Overtreatment Weighed.” The New York Times (Tuesday, September 12, 2017 [sic]): D4.

(Note: ellipses added.)

(Note: the online version of the story has the date Sept. 6, 2017 [sic], and has the same title “Overtreatment Is Common, Doctors Say.”)

The academic study in PLOS One mentioned above is:

Lyu, Heather, Tim Xu, Daniel Brotman, Brandan Mayer-Blackwell, Michol Cooper, Michael Daniel, Elizabeth C. Wick, Vikas Saini, Shannon Brownlee, and Martin A. Makary. “Overtreatment in the United States.” PLOS ONE 12, no. 9 (2017): e0181970.

After a Century an Important Serendipitous Health Hunch Is Pursued

All of us (you, me, dogs, and physicians) observe patterns all the time. Some of the patterns, if pursued, could make the world much better. When a physician observes a pattern, even one they cannot articulately describe or justify, they could change their practices, curing more patients, saving more lives. But they are constrained from deviating from mainstream protocols by government regulations, insurance company rules, hospital administrators, and potential lawsuits. How many serendipitous discoveries that would help us flourish are delayed a century, or even totally snuffed out?

(p. C2) . . . my eye was drawn to a new study in the New England Journal of Medicine finding that hysterosalpingography cured some cases of infertility. Hystero refers to the uterus. Salpingo, I knew, relates to the fallopian tubes that funnel eggs to the uterus. Ography relates to imaging—but how could taking a picture of reproductive organs cure anything?

Doctors use hysterosalpingography to see if there are blockages that could be causing fertility problems.

. . .

To look at blockages, technicians have to introduce a teaspoon or two of a dye that’s opaque to X-rays. How that material is introduced, it turns out, is the key to the procedure’s effect on childlessness.

. . .

Smaller studies had given the scientists an idea of what to do next. They randomly chose half of the women to get the X-ray-opaque dye dissolved in oil, while the other half got the dye in water.

. . .

In an average of three months, whether treated or not, about 40% of the women receiving the oil-based dye material became pregnant, while only 29% of the women who got the water-based dye material conceived.

Hysterosalpingography is exactly a century old this year. Luckily, some astute doctors guessed that the method of taking a picture was having an unintended fertility effect, and now research has backed this up. Such serendipity in medical progress is neatly captured by a saying of the great French biologist Louis Pasteur about the need to be ready to see the unexpected: “In the fields of observation, chance only favors the prepared mind.”

The realization that supposedly inert oil could help to fulfill some couples’ dreams has built slowly. No one knows exactly how it works.

For the full commentary see:

Melvin Konner. “Mind & Matter; Can Just Taking a Picture Help to Treat Infertility?” The Wall Street Journal (Saturday, July 29, 2017 [sic]): C2.

(Note: ellipses added.)

(Note: the online version of the commentary has the date July 26, 2017 [sic], and has the same title as the print version. The Latin words in the first quoted sentence appear in italics in the original version.)

The New England Journal of Medicine article discussed in the passages above is:

Dreyer, Kim, Joukje van Rijswijk, Velja Mijatovic, Mariëtte Goddijn, Harold R. Verhoeve, Ilse A.J. van Rooij, Annemieke Hoek, Petra Bourdrez, Annemiek W. Nap, Henrike G.M. Rijnsaardt-Lukassen, Catharina C.M. Timmerman, Mesrure Kaplan, Angelo B. Hooker, Anna P. Gijsen, Ron van Golde, Cathelijne F. van Heteren, Alexander V. Sluijmer, Jan-Peter de Bruin, Jesper M.J. Smeenk, Jacoba A.M. de Boer, Eduard Scheenjes, Annette E.J. Duijn, Alexander Mozes, Marie J. Pelinck, Maaike A.F. Traas, Machiel H.A. van Hooff, Gijsbertus A. van Unnik, Cornelia H. de Koning, Nan van Geloven, Jos W.R. Twisk, Peter G.A. Hompes, and Ben W.J. Mol. “Oil-Based or Water-Based Contrast for Hysterosalpingography in Infertile Women.” New England Journal of Medicine 376, no. 21 (May 25, 2017): 2043-52.