Bayesian Updating, Not Clinical Trials, Is Key to Advancing Medical Knowledge

(p. D8) In the early pandemic era, for instance, airborne transmission of Covid-19 was not considered likely, but in early July the World Health Organization, with mounting scientific evidence, conceded that it is a factor, especially indoors. The W.H.O. updated its priors, and changed its advice.

This is the heart of Bayesian analysis, named after Thomas Bayes, an 18th-century Presbyterian minister who did math on the side. It captures uncertainty in terms of probability: Bayes’s theorem, or rule, is a device for rationally updating your prior beliefs and uncertainties based on observed evidence.

. . .

As Marc Lipsitch, an infectious disease epidemiologist at Harvard, noted on Twitter, Bayesian reasoning comes awfully close to his working definition of rationality. “As we learn more, our beliefs should change,” Dr. Lipsitch said in an interview.

. . .

But there is little point in trying to establish fixed numbers, said Natalie Dean, an assistant professor of biostatistics at the University of Florida.

“We should be less focused on finding the single ‘truth’ and more focused on establishing a reasonable range, recognizing that the true value may vary across populations,” Dr. Dean said. “Bayesian analyses allow us to include this variability in a clear way, and then propagate this uncertainty through the model.”

. . .

Joseph Blitzstein, a statistician at Harvard, delves into the utility of Bayesian analysis in his popular course “Statistics 110: Probability.” For a primer, in lecture one, he says: “Math is the logic of certainty, and statistics is the logic of uncertainty. Everyone has uncertainty. If you have 100 percent certainty about everything, there is something wrong with you.”

By the end of lecture four, he arrives at Bayes’s theorem — his favorite theorem because it is mathematically simple yet conceptually powerful.

“Literally, the proof is just one line of algebra,” Dr. Blitzstein said. The theorem essentially reduces to a fraction; it expresses the probability P of some event A happening given the occurrence of another event B.

“Naïvely, you would think, How much could you get from that?” Dr. Blitzstein said. “It turns out to have incredibly deep consequences and to be applicable to just about every field of inquiry” — from finance and genetics to political science and historical studies. The Bayesian approach is applied in analyzing racial disparities in policing (in the assessment of officer decisions to search drivers during a traffic stop) and search-and-rescue operations (the search area narrows as new data is added). Cognitive scientists ask, ‘Is the brain Bayesian?’ Philosophers of science posit that science as a whole is a Bayesian process — as is common sense.

. . .

Even with evidence, revising beliefs isn’t easy. The scientific community struggled to update its priors about the asymptomatic transmission of Covid-19, even when evidence emerged that it is a factor and that masks are a helpful preventive measure. This arguably contributed to the world’s sluggish response to the virus.

. . .

In 1650, Oliver Cromwell, Lord Protector of the Commonwealth of England, wrote in a letter to the Church of Scotland: “I beseech you, in the bowels of Christ, think it possible you may be mistaken.”

In the Bayesian world, Cromwell’s law means you should always “keep a bit back — with a little bit of probability, a little tiny bit — for the fact that you may be wrong,” Dr. Spiegelhalter said. “Then if new evidence comes along that totally contradicts your main prior belief, you can quickly ditch what you thought before and lurch over to that new way of thinking.”

“In other words, keep an open mind,” said Dr. Spiegelhalter. “That’s a very powerful idea. And it doesn’t necessarily have to be done technically or formally; it can just be in the back of your mind as an idea. Call it ‘modeling humility.’ You may be wrong.”

For the full story, see:

Siobhan Roberts. “Thinking Like an Epidemiologist.” The New York Times (Tuesday, August 4, 2020): D8.

(Note: ellipses added.)

(Note: the online version of the story has the same date as the print version, and has the title “How to Think Like an Epidemiologist.”)

Expense of Clinical Trials Reduce the Incentive to Re-Purpose Old, Cheap, Off-Patent Vaccines

(p. A5) “Retrospective studies are great and they provide some hints, but there are caveats,” said Dr. Shyam Kottilil, a professor of medicine with the Institute of Human Virology at the University of Maryland School of Medicine. “It’s very difficult to establish causality.”

Interest in the cross-protective effects of vaccines has led to efforts to repurpose old vaccines that may have potential to provide at least transient protection against the coronavirus until a specific vaccine against SARS-CoV-2 is developed and proven safe and effective, he said.

“But nobody knows whether this approach will work unless we test them,” Dr. Kottilil said. “To endorse this, you need to do really good randomized clinical trials.” There is little incentive for private companies to invest in expensive trials because the old vaccines are cheap and off-patent, he added.

For the full story, see:

Roni Caryn Rabin. “Are Past Vaccinations a Shield? It’s Doubtful.” The New York Times (Thursday, July 30, 2020): A5.

(Note: the online version of the story has the date July 29, 2020, and has the title “Old Vaccines May Stop the Coronavirus, Study Hints. Scientists Are Skeptical.”)

Dolly Parton Sings and Donates with “Effective Sympathy”

The above is an “embed” from a YouTube video posted by singer (and English Professor) Ryan Cordell. The lyrics were written by Gretchen McCulloch and the tune is from Dolly Parton’s “Jolene.” The YouTube URL is: https://www.youtube.com/watch?v=cCwNQtnI64I

In my book Openness to Creative Destruction: Sustaining Innovative Dynamism, I write about “effective sympathy” which I describe as “actions taken by sympathetic observers that actually save or improve the lives of those who are suffering” (p. 110). I admire Dolly Parton for donating copies of The Little Engine That Could to poor children. I also admire Dolly Parton for donating a million dollars to help start research on the Moderna vaccine for Covid-19. Dolly Parton knows how to practice effective sympathy.

(p. 12) She wrote “I Will Always Love You” and “Jolene” on the same day and built a theme park around herself. She has given memorable onscreen performances as a wisecracking hairstylist and harassed secretary. She even helped bring about the creation of “Buffy the Vampire Slayer.”

Now, Dolly Parton’s fans are crediting her with saving the world from the coronavirus. It’s an exaggerated, tongue-in-cheek claim, to be sure. But for legions of admirers, Ms. Parton’s donation this spring to Vanderbilt University Medical Center, which worked with the drugmaker Moderna to develop a coronavirus vaccine, was another example of how her generosity and philanthropy have made her one of the world’s most beloved artists.

. . .

“Her money helped us develop the test that we used to first show that the Moderna vaccine was giving people a good immune response that might protect them,” Dr. Denison said on Tuesday.

Ms. Parton told the BBC on Tuesday [November 17, 2020] that she was excited to hear her contribution provided a “little seed money that will hopefully grow into something great and help to heal this world.”

. . .

On Monday [November 16, 2020], after Moderna announced that early trials of the vaccine showed a 94.5 percent effectiveness rate, fans reacted rapturously.

. . .

Ryan Cordell, an associate professor of English at Northeastern University in Boston, filmed himself singing a song about the vaccine to the tune of “Jolene.”

For the full story, see:

Maria Cramer. “Dolly: A Star of Country, a Songwriter, a Virus Hero.” The New York Times, First Section (Sunday, November 22, 2020): 12.

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

(Note: the online version of the story has the date Nov. 17, 2020, and has the title “Dolly Parton: Singer, Songwriter, Pandemic Savior?” The online version says that the title of the New York print version was “Dolly: Country Music Legend, Songwriter, Pandemic Hero” and its page number was 8. The title of my National print version was “Dolly: A Star of Country, a Songwriter, a Virus Hero” and its page number was 12.)

My book mentioned above is:

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

The use of The Little Engine That Could to encourage entrepreneurial perseverance is analyzed in:

Yandle, Bruce. “I Think I Can! Does the Little Engine That Could Matter?” Journal of Private Enterprise 26, no. 2 (Spring 2011): 127-42.

The Son of Jonas Salk Calls Operation Warp Speed “Absolutely Extraordinary”

A screen capture from the Replica Edition of the NYT, p. A4 for Thurs., Nov. 18, 2020.

(p. A4) A 76-year-old man in La Jolla, Calif., says he will get a coronavirus but not the way he got a polio vaccine when he was 9 — lined up in the kitchen next to his two siblings. Their father had sterilized the needles and syringes by boiling them on the stove.

The father was Dr. Jonas Salk, who had developed the vaccine.

. . .

At the time, the vaccine had gone through trials with small numbers of children. A trial with 1.8 million children did not begin until the next year, and the vaccine did not receive approval as safe and effective until a year after that — a timetable that he said made the development of coronavirus vaccine candidates in just months “absolutely extraordinary.” He said he had been concerned about pressure from the Trump administration to have a vaccine ready by Election Day. But he also said the decision to back the development of vaccines through Operation Warp Speed, the federal effort to accelerate vaccine development, “was quite positive.”

For the full story, see:

Barron, James. “Coronavirus Update; ‘l Just Didn’t Feel the Shot’.” The New York Times (Wednesday, November 18, 2020): A4.

(Note: ellipsis added.)

(Note: after considerable time spent searching, I was unable to find this article on the nytimes.com web site. I searched on 11/21/20 for the article that had appeared in-print on 11/18/20. In my experience, it is extremely rare for so recent a print article to be missing from the online web site. So, for documentary purposes, I have reproduced a screen capture of the article from the Replica Edition. (For subscribers to the NYT, The Replica Edition provides an online replica of the print edition for the previous 30 days of issues of the NYT.)

“Greatness in Science Often Comes From the Well-Prepared Mind Turning a Chance Observation Into a Major Discovery”

(p. 27) Takuo Aoyagi, a Japanese engineer whose pioneering work in the 1970s led to the modern pulse oximeter, a lifesaving device that clips on a finger and shows the level of oxygen in the blood and that has become a critical tool in the fight against the novel coronavirus, died on April 18 [2020] in Tokyo.

. . .

Mr. Aoyagi’s contribution to medical science was built on decades of innovation and invention. In an essay about Mr. Aoyagi, John W. Severinghaus, a professor emeritus of anesthesia at the University of California, San Francisco, wrote in 2007 that Mr. Aoyagi’s “dream” had been to detect oxygen saturation levels without having to draw blood.

. . .

But he soon ran into a problem. Blood does not flow smoothly like an open tap, but pulses through the body irregularly, thus preventing an accurate recording of dye levels. The problem, however, turned out to be an opportunity. By devising a mathematical formula to correct for this “pulsatile noise,” he created a device that measured oxygen levels with greater accuracy than before.

“Greatness in science, often, as here, comes from the well-prepared mind turning a chance observation into a major discovery,” Dr. Severinghaus wrote.

For the full obituary, see:

John Schwartz and Hikari Hida. “Takuo Aoyagi, 84; Invented Medical Device.” The New York Times, First Section (Sunday, May 3, 2020): 27.

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

(Note: the online version of the obituary was updated June 20, 2020, and has the title “Takuo Aoyagi, an Inventor of the Pulse Oximeter, Dies at 84.”)

The essay about Aoyagi mentioned above is:

Severinghaus, John W. “Takuo Aoyagi: Discovery of Pulse Oximetry.” Anesthesia & Analgesia 105, no. 6 (Dec. 2007): S1-S6.

Least-Well-Off Were Gaining Before Pandemic

(p. A3) U.S. families’ income and wealth rose in the years heading into the coronavirus pandemic, with those in lower-income and lower-wealth categories reaping relatively large gains, the Federal Reserve said in a report on household finances.

. . .

The distribution of wealth between low- and high-income households narrowed slightly in the latest survey period, Fed economists said, a shift from the 2010-to-2016 period when incomes largely stagnated for all but the most well-off after the 2007-2009 recession.

Families in the lowest two income groups recorded large percentage increases in median net worth, suggesting the decadelong expansion benefited a wide swath of society. Net worth rose 37% to $9,800 for the lowest earners, and increased 40% to $44,000 for the second-lowest group. The median net worth of the highest and second-highest groups declined 8% and 9%, respectively.

For the full story, see:

Harriet Torry. “Household Wealth Rose Before Crisis.” The Wall Street Journal (Tuesday, September 29, 2020): A3.

(Note: ellipsis added.)

(Note: the online version of the story was updated Sep. 28, 2020, and has the title “Household Wealth Rose in Years Before Pandemic, Fed Says.”)

“You Can’t Wait for Somebody to Make a Giant Study”

(p. A6) In April [2020], researchers published an article in the Journal of the American Medical Association suggesting many Covid-19 patients with respiratory distress might require a different treatment approach than typically used for ARDS.

. . .

Maurizio Cereda, an anesthesiologist and head of the surgical ICU at the Hospital of the University of Pennsylvania, said doctors normally use standardized tables to match the level of oxygen in the blood with the amount of PEEP needed. Penn tends to use a table with lower PEEP values, he said, but even those lower levels seem to damage the lungs of some of his Covid-19 patients. As a result, he disregards the table entirely at times, he said, even though some in his institution disagree with his approach.

“You can’t wait for somebody to make a giant study,” Dr. Cereda said. “You are alone with your clinical observation. A lot of people don’t feel comfortable with that because they want to have big guidelines. People seem to be afraid they’re going to do something wrong.”

. . .

At Maimonides Medical Center in Brooklyn, critical-care and emergency-medicine doctor Cameron Kyle-Sidell said he was initially seeing much higher mortality rates from Covid19 patients on ventilators than he would have expected from classic ARDS, possibly because physicians were sticking to PEEP levels used to treat traditional ARDS.

“There are people who are treating this the way they would have treated any other ARDS,” he said. “Then there’re people on the flip side—and I am on that flip side—that think you should treat it as a different disease than we treated in the past.”

For the full story, see:

Sarah Toy and Mark Maremont. “Doctors Split on Best Way To Treat Coronavirus Cases.” The Wall Street Journal (Thursday, July 2, 2020): A6.

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

(Note: the online version of the story has the date July 1, 2020, and has the title “Months Into Coronavirus Pandemic, ICU Doctors Are Split on Best Treatment.” The online version quoted above includes a couple of added sentences quoting Dr. Cereda, beyond the single sentence quoted in the print version.)

Natural Experiments Are Equal to Randomized Double-Blind Clinical Trials in Showing Causality

(p. B6) . . . randomized controlled trials are the gold standard in medicine. Using randomization (by, say, flipping a coin to assign patients to a new treatment or not) is the best way to determine whether treatments work.

Unfortunately, randomized trials take time — which is a problem when doctors need answers now. So doctors and public health officials have been turning to available real-world data on patient outcomes and trying to make sense of them.

. . .

“Large-scale randomized evaluations have been less common in economics, prioritizing the need for economists to identify often creative but sometimes narrow natural experiments to estimate the causal effects of treatments,” said Amitabh Chandra, an economist at the Harvard Business School and the Kennedy School of Government.

Ashish Jha, recently appointed the dean of the Brown University School of Public Health, said that while “natural experiments have causal interpretations, typical associational studies in medicine do not, which may make some medical researchers less comfortable interpreting the results.”

. . .   Most doctors can relate to recent comments by the Food and Drug Administration director Stephen Hahn in last week’s congressional pandemic hearing. “In a rapidly moving situation like we have now with Covid-19,” he said, decisions are made “based on the data that’s available to us at the time.”

For the full commentary, see:

Anupam B. Jena and Christopher M. Worsham. “THE UPSHOT; What Coronavirus Researchers Can Learn From Economists.” The New York Times (Thursday, July 2, 2020): B6.

(Note: ellipses added.)

(Note: the online version of the commentary has the date June 30, 2020, and has the same title as the print version.)

Litan and Mankiw Endorse Paying People to Take Vaccine

(p. 5) What’s the best way to get the economy back on track after the Covid-19 recession? Simple: Achieve herd immunity. And what’s the best way to achieve herd immunity? Again, simple: Once a vaccine is approved, pay people to take it.

That bold proposal comes from Robert Litan, an economist at the Brookings Institution. Congress should enact it as quickly as possible.

. . .

Recent research by the University of Chicago economists Austan Goolsbee and Chad Syverson has found that the government-mandated shutdowns account for just a small part of the decline in economic activity. The main reason people aren’t spending is that they are afraid to leave their homes and contract the virus. That hypothesis explains my own behavior. I have not stepped foot on an airplane or inside a restaurant for six months.

. . .

Immunology, meet economics. One of the first principles of economics — perhaps the most important — is that people respond to incentives. Applying this principle to the case at hand, Mr. Litan recommends that the government pay $1,000 to whoever gets the vaccine. With a large enough incentive, most Americans are likely to get vaccinated.

This proposal is textbook economics. (I’ve written some of the textbooks.) As all economics students learn, when an activity has a side effect on bystanders, that effect is called an externality. In the presence of externalities, the famous theorems of economics that justify laissez-faire do not apply. Adam Smith’s vaunted invisible hand can no longer work its magic.

A classic example of a negative externality is pollution, and the simplest and least invasive policy solution is a tax on emissions. In economics-speak, such a tax internalizes the externality: It induces polluters to take the cost of pollution into account by giving them a financial incentive to cut emissions. That’s why I have written here many times that a tax on carbon emissions is the best way to deal with global climate change.

Vaccination confers a positive externality. When you get vaccinated, you benefit not only yourself but also your fellow citizens by helping society take a step toward herd immunity. In this case, internalizing the externality requires not a tax but a subsidy, as Mr. Litan suggests.

For the full commentary, see:

N. Gregory Mankiw. “A Vaccine Subsidy Licks 2 Crises With One Shot.” The New York Times, SundayReview Section (Sunday, September 13, 2020): 5.

(Note: ellipses added.)

(Note: the online version of the commentary has the date Sept. 9, 2020, and has the title “Pay People to Get Vaccinated.”)

The Robert Litan op-ed mentioned above is:

Litan, Robert E. “Want Herd Immunity? Pay People to Take the Vaccine.” Brookings Institute Op-Ed. (Tues., Aug. 18, 2020) URL: https://www.brookings.edu/opinions/want-herd-immunity-pay-people-to-take-the-vaccine/.>

The Goolsbee and Syverson NBER working paper mentioned above is:

Goolsbee, Austan, and Chad Syverson. “Fear, Lockdown, and Diversion: Comparing Drivers of Pandemic Economic Decline 2020.” NBER Working Paper #27432, June 2020.

“Operation Warp Speed, . . . , Is More Imaginative Than the Bureaucratic Norm”

(p. 11) . . . the blundering of the Trump administration, while real and deadly, may not be responsible for the bulk of America’s coronavirus fatalities.

. . .

. . . : the absence of challenge trials for vaccines (in which young, healthy participants agree to be vaccinated and then infected with the virus), the predictable expert resistance to at-home testing. But the most important one was the straightforward bureaucratic calamity at the C.D.C. that delayed effective testing for a fateful month.

An effective president might have addressed some of these problems. (Although Operation Warp Speed, the White House’s vaccine initiative, is more imaginative than the bureaucratic norm.) But overall they are problems with structures and habits rather than personalities — an institutional decadence that predated Trump and will persist when he is gone.

. . .

. . . the third thing you see when you look beyond Trump [is] the fact that so many countries in Western Europe, to say nothing of our neighbors in the Americas, have had death rates similar to ours.

This reality speaks not of exceptionalism but of convergence — and the possibility that the trends of the early 21st century have left us sharing more in common not only with France and Spain but also with Mexico and Brazil than most Americans might expect.

This, too, may matter long after Trump is gone. Where there are crises, in this dispensation, they are likely to be general rather than just American. Where there is decadence, it is the shared experience of late modernity. And if renewal comes to an exhausted West, it will not necessarily come through America alone.

For the full commentary, see:

Ross Douthat. “What Isn’t Trump’s Fault.” The New York Times, SundayReview Section (Sunday, September 13, 2020): 11.

(Note: ellipses added.)

(Note: the online version of the commentary has the date Sept. 12, 2020, and has the same title as the print version.)

Open Offices Reduce Productivity and Spread Diseases

(p. B4) When historians of the early 21st century look back on the pre-Covid era, one of the absurdities they might highlight is the vogue for gigantic, open-plan offices. The apotheosis of this trend of breaking down barriers between co-workers must surely be Facebook Inc.’s 433,555-square-foot Frank Gehry-designed open-plan office at its headquarters in Menlo Park, Calif. Opened in 2015, it’s now a ghost town, a monument to offices vacated by the pandemic.

Cramming cavernous spaces with as many desks as they could hold might have increased serendipitous interactions, but it almost certainly reduced productivity and helped spread communicable diseases, including coronavirus.

. . .

Cue the “dynamic workplace,” a pivot away from the open plan, built on the idea that with fewer employees coming to work on any given day, offices can offer them more flexibility of layout and management.

While open offices and dynamic workplaces share similar components—privacy booths and huddle rooms to escape the hubbub, cafe-like networking spaces, etc.—they’re philosophically distinct. One is intended to be a place where people come (at least) five days a week, and get most of their work done on site. The other is planned for people rotating in and out of the office, on flexible schedules they have more control over than ever.

. . .

Research on hot-desking in office spaces, for example—where employees give up a dedicated space in favor of first-come-first-serve seating—finds that it decreases socialization and trust. This happens because employees figure they might never again see the person they sit next to on a given day, says Dr. Sander. In other studies, employees complain they can’t find their colleagues, that it’s a hassle to find a new spot to work every day, and that such arrangements ignore humans’ innate territoriality and desire to make a space their own.

For the full commentary, see:

Christopher Mims. “Goodbye, Open Office. Hello, ‘Dynamic Workplace.” The Wall Street Journal (Saturday, September 12, 2020): B4.

(Note: ellipses added.)

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