Category: Covid-19

Randomized Controlled Trials Can Obscure “Nuances and Complexities”

(p. A17) You’ve probably heard of the “gold standard”—randomized controlled trials—for evaluating new pharmaceutical therapies, including for Covid-19. Many treatments that showed promise in other studies have turned up muddy results in randomized controlled trials. But that doesn’t mean they’re necessarily ineffective. Doctors and regulators need to consider the totality of medical evidence when treating patients.

. . .

“Randomized trials for some purposes is the gold standard, but only for some purposes,” Harvard’s Donald Berwick, a former health adviser to President Barack Obama, said in an interview with GNS Health Care CEO Colin Hill in 2013. “Context does matter. We’re learning in a very messy world, and the context that neatens up that world may make it hard to know how to manage in the real world.”

. . .

As Thomas Frieden, who directed the Centers for Disease Control and Prevention under Mr. Obama, wrote in a 2017 New England Journal of Medicine article: “Elevating RCTs at the expense of other potentially highly valuable sources of data is counterproductive.” Such limitations affect their use for “urgent health issues, such as infectious disease outbreaks.” He added: “No study design is flawless, and conflicting findings can emerge from all types of studies.”

. . .

Some experts have dismissed the antimalarial hydroxychloroquine, or HCQ, even though more than a dozen observational studies have found it beneficial. A retrospective observational study of Covid-infected nursing-home residents in France, for instance, found those treated with HCQ and azithromycin were 40% less likely to die.

But a few randomized controlled trials found no benefit. A Spanish randomized trial of HCQ for prophylaxis found it didn’t reduce risk of illness among a large group of people exposed in nursing homes, households and health-care settings. Yet two-thirds of the subjects “reported routine use of masks at the time of exposure,” so they were probably less likely to be infected. Nursing-home residents, who may be less likely to wear masks, were 50% less likely to become sick if they took HCQ. But this finding was statistically insignificant, because the trial included only 293 residents.

. . .

Another problem with Covid-19 randomized trials: Patients at different stages of an illness are often assigned the same dosage. Trials don’t reveal differences in how patients respond to a drug at different dosages or illness severity.

Observational studies can do so. Consider a large study by the Mayo Clinic, which found no overall benefit among patients who received a higher-antibody convalescent plasma versus a lower one. Yet the researchers reported a 37% reduction in mortality among patients under 80 who weren’t on a ventilator and received a high-antibody plasma within three days of hospitalizations.

A randomized trial might have obscured these nuances and complexities, denying doctors important information about treatment options. Randomized controlled trials can yield important insights, but it is a medical mistake and a disservice to patients to dismiss other types of evidence.

For the full commentary, see:

Allysia Finley. “Medical Research’s Cross of ‘Gold’ Imperils Covid Treatments.” The Wall Street Journal (Wednesday, September 9, 2020): A17.

(Note: ellipses added.)

(Note: the online version of the commentary has the date Sep. 8, 2020, and has the same title as the print version.)

The review article by Frieden mentioned above is:

Frieden, Thomas R. “Evidence for Health Decision Making — Beyond Randomized, Controlled Trials.” New England Journal of Medicine 377, no. 5 (Aug. 3, 2017): 465-75.

Covid-19 May Shift Restaurants Toward Fewer Workers and More Take-Out, Even in Long Run

(p. B4) Andrew Snow was supposed to be ramping up by now. Mr. Snow, who owns the Golden Squirrel, a restaurant and bar in Oakland’s Rockridge neighborhood, cut his staff of 28 people to two after the pandemic hit.

. . .

Now business is slowing again, as California is averaging about 8,000 new cases a day, about triple the level a month ago. Mr. Snow’s plans to bring back workers over the holiday weekend didn’t come to pass, and he has put further hiring on hold.

“People are scared,” he said in an interview. “The math for having more people doesn’t work out anymore.”

. . .

The longer the pandemic’s disruption, the more likely it is that some jobs will never come back. For instance, a number of restaurants had already switched to counter service, even for fairly high-end meals, to avoid the need for servers who have a hard time affording housing in big cities. Now virtually every restaurant in California is operating around counter service or delivery, and some may not change back.

Mr. Snow, for example, envisions a restaurant where people order at the bar, eat far from other patrons, then leave with a bag of groceries. The Golden Squirrel would have fewer employees, compensating for a less-full restaurant with expanded takeout orders.

“Some of the changes will make us a better business in the future,” Mr. Snow said. “The challenge is getting to that future.”

For the full story, see:

Conor Dougherty. “After Riding a Boom, California Braces for Hard Times.” The New York Times (Monday, July 13, 2020): B1 & B4.

(Note: ellipses added.)

(Note: the online version of the story was updated July 14, 2020, and has the title “California, After Riding a Boom, Braces for Hard Times.”)

Masks Blocked Covid-19 at Hair Salon

(p. A6) Vigilant mask wearing might have spared nearly 140 people from catching the coronavirus at a hair salon in Missouri, according to a report published on Tuesday [July 14, 2020] by the Centers for Disease Control and Prevention. In May [2020], the people interacted with two hair stylists with confirmed coronavirus infections, but none ended up showing symptoms of Covid-19.

. . .

But policies instructing locals to cover their mouths and noses, put in place by the city of Springfield and by the salon where the stylists worked, Great Clips, appear to have played a substantial role in curbing the spread of disease.

For the full story, see:

Katherine J. Wu. “Report on Hair Salon Affirms Value of Masks.” The New York Times (Thursday, July 16, 2020): A6.

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

(Note: the online version of the story was updated July 17 [sic], 2020, and has the title “2 Stylists Had Coronavirus, but Wore Masks. 139 Clients Didn’t Fall Sick.”)

The CDC report mentioned above is:

Hendrix MJ, Walde C, Findley K, Trotman R. Absence of Apparent Transmission of SARS-CoV-2 from Two Stylists After Exposure at a Hair Salon with a Universal Face Covering Policy — Springfield, Missouri, May 2020. MMWR Morb Mortal Wkly Rep 2020;69:930-932.

Covid-19 May Make New York City “Cheaper, Messier, More Diverse”

(p. B1) Cities are remarkably resilient. They have risen from the ashes after being carpet-bombed and hit with nuclear weapons. “If you think about pandemics in the past,” noted the Princeton economist Esteban Rossi-Hansberg, “they didn’t destroy cities.”

. . .

So even as the Covid-19 death toll rises in the nation’s most dense urban cores, economists still mostly expect them to bounce back, once there is a vaccine, a treatment or a successful strategy to contain the virus’s spread. “I end up being optimistic,” said the Harvard economist Edward Glaeser. “Because the downside of a nonurban world is so terrible that we are going to spend whatever it takes to prevent that.”

. . .

(p. B5) Mr. Glaeser and colleagues from Harvard and the University of Illinois studied surveys tracking companies that allowed their employees to work from home at least part of the time since March. Over one-half of large businesses and over one-third of small ones didn’t detect any productivity loss. More than one in four reported a productivity increase.

Moreover, the researchers found that about four in 10 companies expect that 40 percent of their employees who switched to remote work during the pandemic will keep doing so after the crisis, at least in part. That’s 16 percent of the work force. Most of these workers are among the more highly educated and well paid.

. . .

“Everybody agrees on what are the key forces,” said Gilles Duranton, an economist at the Wharton School of the University of Pennsylvania. “The question is which will play out, and where are the tipping points?” One of the big remaining questions is whether remote work will prove sustainable. The productivity increases captured in the surveys examined by Mr. Glaeser’s team might prove fleeting.

. . .

Consider life in a reconfigured New York City. Rents are lower, after the departure of many of its bankers and lawyers. There are fewer fancy restaurants, but probably still many cheaper ones. People with lower incomes, including the young, can again afford to live in town. City services may be reduced, but if a fifth or more of workers aren’t going to the office on any given day it will be easier to get around.

Mr. Duranton argues that the cities that will be devastated by Covid-19 are the ones that have been falling for a long time: the Rochesters and the Binghamtons, which lost their sustenance once the manufacturing industries that supported them through much of the 20th century folded or moved away.

But for a city like New York, he said, Covid-19 offers an opportunity for redemption. “New York was running into a dead end, turning into a paradise for the rich,” he said. “Culturally dead.” Moving back to a cheaper, messier, more diverse equilibrium may carry a silver lining.

For the full story, see:

Eduardo Porter. “If Workers Opt Out, Star Cities May Dim.” The New York Times (Tuesday, July 21, 2020): B1 & B5.

(Note: ellipses added.)

(Note: the online version of the story has the same date as the print version,s and has the title “Coronavirus Threatens the Luster of Superstar Cities.”)

The study co-authored by Glaeser and mentioned above is:

Bartik, Alexander W., Zoe Cullen, Edward L. Glaeser, Michael Luca, and Christopher Stanton. “What Jobs Are Being Done at Home During the Covid-19 Crisis? Evidence from Firm-Level Surveys.” Harvard Business School Division of Research Working Paper #20-138, (July 2020).

“There’s No Wolf Warrior Coming to” Rescue the “Little Pinks”

(p. B1) When China came under attack online, Mr. Liu was one of the legions of Chinese students studying abroad who posted in its defense. He condemned the pro-democracy protests in Hong Kong, which he saw as an effort to split a uniting China. After President Trump called the coronavirus the “Chinese virus,” Mr. Liu turned to Twitter to correct those who used the term.

“I was a real little pink,” he said, using a somewhat derogatory term for the young, Communist-red Chinese nationalists who use the internet as a patriotic battleground to fight those who disparage China.

Then Mr. Liu, 21, discovered that the country he had long defended didn’t want him back.

. . .

Mr. Liu and many other countless Chinese people stranded overseas are, for the first time, running afoul of one of their country’s bedrock political prin-(p. B5)ciples: National interests come before an individual’s needs.

. . .

“Can you imagine what it was like when one day someone told you what you believed firmly wasn’t actually true?” Mr. Liu said.

. . .

“In the real world, there’s no wolf warrior coming to my rescue,” a Chinese student in Japan posted on Weibo.

. . .

While the students were outspoken in their anonymous social media comments, they were more reserved in interviews. Mr. Liu, for example, focused his frustration on China’s aviation regulator, which recently backed down after U.S. officials challenged its limits on foreign airlines. Ms. Leng, of Troy University, said she understood the regulator’s motivations.

But some admitted to what might be a new feeling: fear. The student from Japan who invoked “Wolf Warrior 2” said she feared retribution by the Chinese government if she spoke to me.

Then she invited me into a WeChat group of nearly 500 Chinese students exchanging information about flights, visas, schools and frustrations. They told one another not to give news interviews, not even to the Chinese media, for fear of government punishment.

When they sometimes couldn’t help curse the government or the policy, someone would quickly warn that they had better shut up or risk losing their WeChat accounts or even being invited for a chat once they’re back in China.

One student, after being warned, posted an emoticon of the 12 core socialist values that every Chinese citizen is supposed to live by, posting it five times in a row, as if pledging his loyalty to the surveillance state.

“I grew up under the red flag and received the red education,” Mr. Liu said to me. “But what can I say now?”

For the full story, see:

Li Yuan. “THE NEW NEW WORLD; Little Pinks’ Rethink China After Being Trapped Abroad.” The New York Times (Tuesday, June 30, 2020): B1 & B5.

(Note: ellipses added.)

(Note: the online version of the story has the date June 24, 2020, and has the title “THE NEW NEW WORLD; Trapped Abroad, China’s ‘Little Pinks’ Rethink Their Country.”)

Our Government Sends 19-Year-Olds to War but Does Not Allow Them to Try High-Risk, High-Reward Covid-19 Drugs and Vaccines

(p. A11) “Many drug programs are suspended or not pursued at all—not because of flaws in the science but because of commercial and strategic reasons,” Mr. Milken says. Researchers screen those programs, and he calls in his partners either to fund the ideas or promote their development at other companies if the inventors make them available.

It’s a niche in the pharmaceutical world that public funding can’t fill. Mr. Milken sustains a model “where a person could just give me a five-page summary and get a meeting. Government isn’t going to fund that, but philanthropy does.” “These little companies,” he adds—“they’re not Johnson & Johnson, they’re not Novartis, they’re not Amgen. They need financial capital.”

. . .

Mr. Milken’s deals not tinged by controversy, such as his 1983 issuance of bonds to finance telecom company MCI’s long-distance network, show the same preference that shapes his philanthropy: high risk for a high reward.

. . .

A perennial struggle for Mr. Milken has been to convince regulators to share that urgency. He says drug trials generally are too rigid: “We send 19-year-olds into war zones knowing that no matter what we do, some number—greater than zero—will lose their lives or their limbs. But we tell a patient who is going to die not to try something because it could be dangerous.”

Nonetheless, the partners he’s made in his search for cures prove that imagination and activity are still scattered through the country. Discussing the coronavirus with biotech founders and Nobel Prize winners, Mr. Milken says he’s been “thrust back into the 1970s and early ’80s, where any time someone had a new idea—a new company, a passion for something—I had set aside time every day to listen.” On the day a vaccine or effective cure for Covid-19 is finally announced, Americans will owe thanks to such risk takers, who Mr. Milken says “invest in where the world is going, not where it is.”

For the full interview, see:

Mene Ukueberuwa, interviewer. “THE WEEKEND INTERVIEW; What Would You Risk for a Faster Cure?” The Wall Street Journal (Saturday, May 2, 2020): A11.

(Note: ellipses added.)

(Note: the online version of the interview has the date May 1, 2020, and has the same title as the print version.)

Former FDA Research Virologist Suggests “Accelerated Approvals” of Covid-19 Vaccines

(p. A15) Covid-19 is a genuine emergency. Drug and biotech companies and academic institutions are doing their part, and regulators need to, as well. Having been a research virologist who spent 15 years at the FDA as the agency’s “biotechnology czar,” I have some suggestions:

. . .

• The FDA should issue “accelerated approvals” after testing in only limited populations. Additional subgroups—children, pregnant women, etc.—can be tested after approval. The accelerated approvals should be granted before the duration of postvaccination immunity has been ascertained. More-comprehensive trials can then confirm safety, efficacy and the length of time that immunity lasts.

• Establish reciprocity of approvals between the FDA and trusted counterparts in certain foreign countries (Australia, Canada, New Zealand, Japan, the Scandinavian countries and the European Medicines Agency), so that if one of them approves a vaccine, it is automatically approved in the other countries.

For the full commentary, see:

Henry I. Miller. “A Covid Vaccine: Faster, Please.” The Wall Street Journal (Thursday, April 23, 2020): A15.

(Note: ellipsis added.)

(Note: the online version of the commentary has the date April 22, 2020, and has the title “A Coronavirus Vaccine: Faster, Please.”)

Fauci Criticizes Russia for Allowing Citizens to Take Covid-19 Vaccine After Passing Phase 2 Safety Trials

Milton Friedman thought that, at the very least, the FDA should allow Americans the freedom to choose to take drugs or vaccines after their safety has been established (basically meaning after passing the Phase 2 safety trials). Isn’t it strange that in the FDA’s United States, citizens may not do so, but in Putin’s authoritarian Russia, citizens are allowed that choice?

(p. A4) In a panel discussion, Dr. Anthony S. Fauci, the nation’s top infections disease expert, criticized Russia’s rushed clearance of a coronavirus vaccine. The vaccine, called Sputnik V, was approved without evidence that Phase 3 clinical trials had been completed, an essential part of the development pipeline to prove a product is safe and effective in people.

. . .

Dr. Fauci called attention to the many other coronavirus vaccines vying for eventual clearance, including several that are in Phase 3 trials in the United States. The process for testing vaccines can last months and usually involves thousands of people.

“So if we wanted to take the chance of hurting a lot of people or giving them something that doesn’t work, we could start doing this, you know, next week if we wanted to,” Dr. Fauci said. “But that’s not the way this works.”

For the full story, see:

Barron, James. “Coronavirus Update.” The New York Times (Thursday, August 11, 2020): A4.

(Note: ellipsis added.)

(Note: the online version of the story was updated August 14, 2020, and has the title “U.S. Coronavirus Death Toll Reflects Sun Belt Outbreaks.” Where there are slight differences in wording between the versions in the passages quoted, the online version appears above. The online version does not list an author. I cite James Barron, who is listed as the author in the print version.)

Environmentalism Is a “Substitute Religion” Offering “Purpose and Transcendence”

(p. A13) There is a recurring puzzle in the history of the environmental movement: Why do green activists keep promoting policies that are harmful not only to humans but also to the environment? Michael Shellenberger is determined to solve this problem, and he is singularly well qualified.

He understands activists because he has been one himself since high school, when he raised money for the Rainforest Action Network. Early in his adult career, he campaigned to protect redwood trees, promote renewable energy, stop global warming, and improve the lives of farmers and factory workers in the Third World. But the more he traveled, the more he questioned what Westerners’ activism was accomplishing for people or for nature.

He became a different kind of activist by helping start a movement called ecomodernism, the subject of “Apocalypse Never: Why Environmental Alarmism Hurts Us All.” He still wants to help the poor and preserve ecosystems, but through industrialization instead of “sustainable development.” He’s still worried about climate change, but he doesn’t consider it the most important problem today, much less a threat to humanity’s survival—and he sees that greens’ favorite solutions are making the problem worse.

. . .

Mr. Shellenberger makes a persuasive case, lucidly blending research data and policy analysis with a history of the green movement and vignettes of people in poor countries suffering the consequences of “environmental colonialism.” He realizes, though, that rational arguments alone won’t convince devout environmentalists. “I was drawn toward the apocalyptic view of climate change twenty years ago,” he writes. “I can see now that my heightened anxiety about climate reflected underlying anxiety and unhappiness in my own life that had little to do with climate change or the state of the natural environment.”

For him and so many others, environmentalism offered emotional relief and spiritual satisfaction, giving them a sense of purpose and transcendence. It has become a substitute religion for those who have abandoned traditional faiths, as he explains in his concluding chapter, “False Gods for Lost Souls.” Its priests have been warning for half a century that humanity is about to be punished for its sins against nature, and no matter how often the doomsday forecasts fail, the faithful still thrill to each new one.

For the full review, see:

John Tierney. “BOOKSHELF; False Gods for Lost Souls.” The Wall Street Journal (Monday, June 22, 2020): A13.

(Note: ellipsis added.)

(Note: the online version of the review has the date June 21, 2020, and has the title “BOOKSHELF; ‘Apocalypse Never’ Review: False Gods for Lost Souls.”)

The book under review is:

Shellenberger, Michael. Apocalypse Never: Why Environmental Alarmism Hurts Us All. New York: HarperCollins Books, 2020.

Viruses Mutate More Nimbly Than Therapies Hobbled by FDA Regulations

(p. A7) In a laboratory in New York City, researchers coaxed a key piece of the coronavirus — its infamous outer “spike” — to mutate so that it became invisible to disease-fighting antibodies, according to a new study that has not yet been published in a scientific journal.

The provocative finding should not set off alarm bells, experts said. The altered spikes were not attached to the real coronavirus, which mutates at a much slower pace than most laboratory viruses. But the study does underscore the need for treatments and vaccines that attack the virus in different ways, so that if the pathogen manages to evade one approach, another will be waiting in the wings.

“It’s an old story for virology,” said Dr. Sallie Permar, a virologist and pediatrician at Duke University who was not involved in the study. “If you only target one little region, that virus is going to find a way to get away from it. It’s why viruses are so successful in this world.”

. . .

Several types of monoclonal antibodies are now in clinical trials. If all goes well, such concoctions might not only treat coronavirus infections but also prevent them. That could help millions of people, especially as the world awaits a vaccine, said Akiko Iwasaki, an immunologist at Yale University who was not involved in the study.

But the new findings also hint that single-antibody formulations “may not be as successful,” Dr. Taylor said, at least in the long term. Developing a cocktail containing a diverse blend of antibodies could be a safer bet.

Such mixtures would also more accurately mimic the body’s natural response to the coronavirus. In the study, viruses flushed with samples of convalescent plasma — fractions of blood donated by people who have recovered from Covid-19 — struggled to infect cells.

Some scientists, including those at American biotechnology company Regeneron, are already attempting this combo approach, mixing two potent types of monoclonal antibodies into a single treatment.

But Dr. Iwasaki pointed out that antibody cocktails might be tougher to bring to market. “Every time you make a drug, you get approval for each component separately,” she said. . . .

The lesson of diversity might be even more powerful for vaccines, which can marshal a multifaceted immune response. Some immune cells and molecules will be tailored to home in on the spike, whereas others might prefer other parts of the virus. Vaccines that present the body with many pieces of the coronavirus, rather than the spike alone, could have a better shot at triggering a suite of these defenses, said Dr. Taia Wang, an immunologist at Stanford University who was not involved in the study.

For the full story, see:

Katherine J. Wu. “Experiment on Spike Protein Shows Obstacles of Mutation.” The New York Times (Wednesday, July 29, 2020): A7.

(Note: ellipsis added.)

(Note: the online version of the story has the date July 28, 2020, and has the title “The Coronavirus Could Dodge Some Treatments, Study Suggests.” The online version has an extra paragraph that does not appear in the print version. In my quotations above, I stick to the print version.)

Paper Towels Spread Fewer Germs Than Hot-Air Drying

(p. R1) In the age of coronavirus, handwashing can save lives. But proper hand-drying matters, too.

“It might sound pedantic, but it’s actually critical,” says John Gammon, professor of infection prevention and control at Swansea University in the U.K.

Prof. Gammon was the lead author of a review of hand-drying research and published his findings in the March 2019 issue of the Journal of Infection Prevention. His paper, “The Neglected Element of Hand Hygiene,” examined the effectiveness of paper towels, cloth towels and dryers that use hot air or high-velocity air.

In a clinical situation, such as a hospital, disposable paper towels are generally the quickest, most efficient and hygienic method of hand drying. “The mechanical action of rubbing with paper towels has an effect on reducing microorganisms on hands,” Prof. Gammon says. Paper towels are also less likely to spread germs into the surrounding environment than hot-air and high-velocity air dryers, he adds.

For the full story, see:

Beth DeCarbo. “The Best Way to Dry Your Hands.” The Wall Street Journal (Friday, April 3, 2020): R1.

(Note: the online version of the story was updated April 2, 2020, and has the title “You’ve Perfected Your Handwashing Technique. Here’s How to Dry Them.” Where there is a slight difference in wording between the versions, the passages quoted above follow the online version.)

Gammon’s academic paper, mentioned above, is:

Gammon, John, and Julian Hunt. “The Neglected Element of Hand Hygiene – Significance of Hand Drying, Efficiency of Different Methods and Clinical Implication: A Review.” Journal of Infection Prevention 20, no. 2 (March 2019): 66-74.