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3 Covid-19 Trials Have Been Paused for Safety. That’s a Good Thing.

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This week, two high-profile, late-stage clinical trials — Johnson & Johnson’s test of a coronavirus vaccine and Eli Lilly’s study of a Covid-19 drug — were put on pause because of possible safety concerns. Just a month earlier, AstraZeneca’s vaccine trial was paused after two volunteers became seriously ill.

Clinical trials experts said these delays were comforting, in a way: They show that the researchers were following proper safety procedures. But for now, details about the nature of the volunteers’ illnesses are scant. And although pauses of vaccine trials are not unusual, some experts said that pausing treatment trials — like that of Eli Lilly’s antibody drug — is rarer, and perhaps more worrisome.

That trial was testing the treatment on hospitalized patients — a group that was already sick, and in which declines in health would not be surprising. So for a trial like that one to be paused, the safety concerns must have been significant, they said.

“I’ve done 50-plus monitoring committees, and it’s quite a rare thing to do,” said Tim Friede, a biostatistician at University Medical Center Göttingen in Germany, referring to his role as a safety monitor for drug trials.

For now, the companies behind the trials aren’t saying much. In a statement in September, AstraZeneca said it paused its trial to investigate “a single event of an unexplained illness.” But two vaccinated volunteers reportedly developed the same condition, an inflammation of the spinal cord called transverse myelitis.

Johnson & Johnson said that it was pausing its vaccine trial because of an “unexplained illness.” Eli Lilly’s trial of the antibody treatment was paused because of a — so far undisclosed — health difference between the group that received the drug and the group that received a placebo.

When people volunteer for a late-stage trial, known as Phase 3, they randomly get a treatment or a placebo, and neither they nor their doctor knows which one they received. In the weeks that follow, they’re carefully monitored. People in a vaccine trial may get a checkup each month and record any symptoms they experience in a journal. People who get a drug while they’re hospitalized may be given blood tests and medical exams.

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Mild symptoms, like a minor rash or a headache, aren’t enough to pause a trial. But when investigators notice a serious problem — known as an “adverse event” — they have to report it to the sponsoring companies. And the sponsors then have to report to both the Food and Drug Administration and their independent advisers, known as data and safety monitoring boards.

If the board or the company judges the adverse event to be particularly concerning, they may put the trial on pause — even without yet knowing if the event happened to someone who got the treatment or the placebo.

Dr. Paul Offit, a professor at the University of Pennsylvania and a member of the F.D.A.’s vaccine advisory panel, said that pausing a trial is a huge logistical challenge — especially for one like Johnson & Johnson’s, with plans for 60,000 volunteers in 10 countries.

“It’s this big warship that you just stop moving,” Dr. Offit said.

Once a trial is paused, a safety board may ask for a volunteer who experienced an adverse event to be “unblinded” — in other words, to find out if the volunteer got the placebo or the treatment. If the volunteer received a placebo, then the treatment can’t be the cause of the event and the trial can continue.

If it turns out that the volunteer got the treatment, the board does a flurry of detective work. The members look over the medical records. They may ask for more information about volunteers’ health or even order new tests — not just for the people who experienced adverse events, but for everyone in the trial.

The board uses this evidence to come to a conclusion about whether the treatment most likely had anything to do with the event. On very rare occasions, for example, some vaccines can cause a nerve disorder called Guillain-Barré syndrome. But the condition takes weeks to develop. If a volunteer shows signs of Guillain-Barré syndrome on the day of a vaccine injection, it can’t be the cause.

Regulators then review the decision of these boards and may accept it or ask for more information. For trials that are running in several countries at once, this review can make pausing a trial even more of a challenge. After AstraZeneca paused its global trials on Sept. 6 for a review, regulators in Brazil, India, Japan, South Africa and the United Kingdom all gave the green light for the trial to resume. But American regulators are still keeping the U.S. trial on pause as they continue to look over the evidence.

If a safety board rules that an adverse event most likely was not a result of the vaccine or treatment, it may allow the trial to start up again. If, on the other hand, there’s some urgent problem — a contaminated batch of drugs, for example — the trial may have to stop. When the evidence isn’t so clear, the board may let the trial resume with extra tests or exams. A second case of the same event might be more common than you would expect from chance, forcing the trial to end.

But there are some important differences in the way pauses work in trials for vaccines — like Johnson & Johnson and AstraZeneca’s — and for drugs like Eli Lilly’s. Vaccines are designed to be given to millions or billions of healthy people. So they require extreme safety. If even one person in a vaccine trial gets sick, that warrants a closer look.

“It is not at all uncommon for this to happen,” said Dr. Anna Durbin, a professor of international health at the Johns Hopkins Bloomberg School of Public Health. “In the vast majority of cases, the trial continues.”

ImageTest kits for new patients at a trial site for Regeneron- and Eli Lilly-developed treatments in Mesa, Ariz.
Credit…Adriana Zehbrauskas for The New York Times

And in a trial as big as Johnson & Johnson’s, you expect some sort of adverse event to happen, regardless of the potential risks of the treatment being tested. It would be strange if investigators reported nothing. “Then you’re concerned that the surveillance system for adverse events isn’t working,” said Saad Omer, the director of the Yale Institute for Global Health.

Dr. Stanley Plotkin, a vaccine expert and professor emeritus at the University of Pennsylvania, was not surprised that two vaccine trials were paused. After all, a huge number of vaccine candidates — 43 to date — are being tested in clinical trials. Many of them are based on cutting-edge designs that have never been licensed before. “It means a lot of new ground is being broken,” he said, “so people are being doubly careful.”

But pauses of treatment trials are not as common. There’s a simple reason for the difference: The people getting drugs have a disease, sometimes a very serious one. For Eli Lilly’s trial, for example, researchers are only recruiting people who are already hospitalized with Covid-19. In such a group of seriously ill people, even a death would, sadly, not come as a great shock.

As a result, the evidence for an adverse event often has to reach a higher bar to pause a drug trial. Indeed, that seems to be the case with the paused Covid-19 trials. One patient was enough to cause Johnson & Johnson to halt its trial. But a National Institutes of Health spokeswoman said the Eli Lilly trial was paused because the safety board found that the patients who had received the antibodies showed a different “clinical status” than those who had received a placebo.

Dr. Eric Topol, a professor of molecular medicine at Scripps Research in La Jolla, California, is still hopeful about the antibody treatment. He observed that both Eli Lilly and another company, Regeneron, have already given monoclonal antibodies to thousands of people with Covid-19 without any previous reports of problems (although some of the trials were on people with relatively mild cases). “I’m still fairly optimistic,” he said.

Although pausing trials is a standard procedure, it’s not a familiar one. Before the pandemic focused the world’s attention on clinical trials, researchers would pause trials and investigate adverse events without much notice. If a paused trial has to be abandoned, that pause might get mentioned a year later in a scientific paper about the trial.

But if a trial resumes and ends successfully, then the pause may just seem like an irrelevant detail. “You may very well never mention that,” said Peter G. Lurie, president of the Center for Science in the Public Interest and former associate commissioner for public health strategy and analysis at the Food and Drug Administration.

But in a pandemic — especially one in which the president of the United States claims without justification that a vaccine will be ready by Election Day and that monoclonal antibodies are a miraculous “cure” for Covid-19 — these pauses are drawing attention like never before. “That is something we are not used to at all,” Dr. Friede said.

Nevertheless, Dr. Friede said, it is vital that researchers stick to their protocols, no matter the pressure they feel to speed things up. “That’s a very difficult situation to be in, but I think it’s very important that we keep up the standards,” he said.

No matter what the outcome of the pauses, many experts found the caution heartening. “It shows me that people are taking safety very seriously,” Dr. Durbin said. “This is an example of how things are supposed to work.”

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The Trump campaign celebrated a growth record that Democrats downplayed.

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The White House celebrated economic growth numbers for the third quarter released on Thursday, even as Joseph R. Biden Jr.’s presidential campaign sought to throw cold water on the report — the last major data release leading up to the Nov. 3 election — and warned that the economic recovery was losing steam.

The economy grew at a record pace last quarter, but the upswing was a partial bounce-back after an enormous decline and left the economy smaller than it was before the pandemic. The White House took no notice of those glum caveats.

“This record economic growth is absolute validation of President Trump’s policies, which create jobs and opportunities for Americans in every corner of the country,” Mr. Trump’s re-election campaign said in a statement, highlighting a rebound of 33.1 percent at an annualized rate. Mr. Trump heralded the data on Twitter, posting that he was “so glad” that the number had come out before Election Day.

The annualized rate that the White House emphasized extrapolates growth numbers as if the current pace held up for a year, and risks overstating big swings. Because the economy’s growth has been so volatile amid the pandemic, economists have urged focusing on quarterly numbers.

Those showed a 7.4 percent gain in the third quarter. That rebound, by far the biggest since reliable statistics began after World War II, still leaves the economy short of its pre-pandemic levels. The pace of recovery has also slowed, and now coronavirus cases are rising again across much of the United States, raising the prospect of further pullback.

“The recovery is stalling out, thanks to Trump’s refusal to have a serious plan to deal with Covid or to pass a new economic relief plan for workers, small businesses and communities,” Mr. Biden’s campaign said in a release ahead of Thursday’s report. The rebound was widely expected, and the campaign characterized it as “a partial return from a catastrophic hit.”

Economists have warned that the recovery could face serious roadblocks ahead. Temporary measures meant to shore up households and businesses — including unemployment insurance supplements and forgivable loans — have run dry. Swaths of the service sector remain shut down as the virus continues to spread, and job losses that were temporary are increasingly turning permanent.

“With coronavirus infections hitting a record high in recent days and any additional fiscal stimulus unlikely to arrive until, at the earliest, the start of next year, further progress will be much slower,” Paul Ashworth, chief United States economist at Capital Economics, wrote in a note following the report.

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Black and Hispanic workers, especially women, lag in the U.S. economic recovery.

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The surge in economic output in the third quarter set a record, but the recovery isn’t reaching everyone.

Economists have long warned that aggregate statistics like gross domestic product can obscure important differences beneath the surface. In the aftermath of the last recession, for example, G.D.P. returned to its previous level in early 2011, even as poverty rates remained high and the unemployment rate for Black Americans was above 15 percent.

Aggregate statistics could be even more misleading during the current crisis. The job losses in the initial months of the pandemic disproportionately struck low-wage service workers, many of them Black and Hispanic women. Service-sector jobs have been slow to return, while school closings are keeping many parents, especially mothers, from returning to work. Nearly half a million Hispanic women have left the labor force over the last three months.

“If we’re thinking that the economy is recovering completely and uniformly, that is simply not the case,” said Michelle Holder, an economist at John Jay College in New York. “This rebound is unevenly distributed along racial and gender lines.”

The G.D.P. report released Thursday doesn’t break down the data by race, sex or income. But other sources make the disparities clear. A pair of studies by researchers at the Urban Institute released this week found that Black and Hispanic adults were more likely to have lost jobs or income since March, and were twice as likely as white adults to experience food insecurity in September.

The financial impact of the pandemic hit many of the families that were least able to afford it, even as white-collar workers were largely spared, said Michael Karpman, an Urban Institute researcher and one of the studies’ authors.

“A lot of people who were already in a precarious position before the pandemic are now in worse shape, whereas people who were better off have generally been faring better financially,” he said.

Federal relief programs, such as expanded unemployment benefits, helped offset the damage for many families in the first months of the pandemic. But those programs have mostly ended, and talks to revive them have stalled in Washington. With virus cases surging in much of the country, Mr. Karpman warned, the economic toll could increase.

“There could be a lot more hardship coming up this winter if there’s not more relief from Congress, with the impact falling disproportionately on Black and Hispanic workers and their families,” he said.

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Ant Challenged Beijing and Prospered. Now It Toes the Line.

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As Jack Ma of Alibaba helped turn China into the world’s biggest e-commerce market over the past two decades, he was also vowing to pull off a more audacious transformation.

“If the banks don’t change, we’ll change the banks,” he said in 2008, decrying how hard it was for small businesses in China to borrow from government-run lenders.

“The financial industry needs disrupters,” he told People’s Daily, the official Communist Party newspaper, a few years later. His goal, he said, was to make banks and other state-owned enterprises “feel unwell.”

The scope of Mr. Ma’s success is becoming clearer. The vehicle for his financial-technology ambitions, an Alibaba spinoff called Ant Group, is preparing for the largest initial public offering on record. Ant is set to raise $34 billion by selling its shares to the public in Hong Kong and Shanghai, according to stock exchange documents released on Monday. After the listing, Ant would be worth around $310 billion, much more than many global banks.

The company is going public not as a scrappy upstart, but as a leviathan deeply dependent on the good will of the government Mr. Ma once relished prodding.

More than 730 million people use Ant’s Alipay app every month to pay for lunch, invest their savings and shop on credit. Yet Alipay’s size and importance have made it an inevitable target for China’s regulators, which have already brought its business to heel in certain areas.

These days, Ant talks mostly about creating partnerships with big banks, not disrupting or supplanting them. Several government-owned funds and institutions are Ant shareholders and stand to profit handsomely from the public offering.

The question now is how much higher Ant can fly without provoking the Chinese authorities into clipping its wings further.

Excitable investors see Ant as a buzzy internet innovator. The risk is that it becomes more like a heavily regulated “financial digital utility,” said Fraser Howie, the co-author of “Red Capitalism: The Fragile Financial Foundation of China’s Extraordinary Rise.”

“Utility stocks, as far as I remember, were not the ones to be seen as the most exciting,” Mr. Howie said.

Ant declined to comment, citing the quiet period demanded by regulators before its share sale.

The company has played give-and-take with Beijing for years. As smartphone payments became ubiquitous in China, Ant found itself managing huge piles of money in Alipay users’ virtual wallets. The central bank made it park those funds in special accounts where they would earn minimal interest.

After people piled into an easy-to-use investment fund inside Alipay, the government forced the fund to shed risk and lower returns. Regulators curbed a plan to use Alipay data as the basis for a credit-scoring system akin to Americans’ FICO scores.

China’s Supreme Court this summer capped interest rates for consumer loans, though it was unclear how the ceiling would apply to Ant. The central bank is preparing a new virtual currency that could compete against Alipay and another digital wallet, the messaging app WeChat, as an everyday payment tool.

Ant has learned ways of keeping the authorities on its side. Mr. Ma once boasted at the World Economic Forum in Davos, Switzerland, about never taking money from the Chinese government. Today, funds associated with China’s social security system, its sovereign wealth fund, a state-owned life insurance company and the national postal carrier hold stakes in Ant. The I.P.O. is likely to increase the value of their holdings considerably.

“That’s how the state gets its payoff,” Mr. Howie said. With Ant, he said, “the line between state-owned enterprise and private enterprise is highly, highly blurred.”

China, in less than two generations, went from having a state-planned financial system to being at the global vanguard of internet finance, with trillions of dollars in transactions being made on mobile devices each year. Alipay had a lot to do with it.

Alibaba created the service in the early 2000s to hold payments for online purchases in escrow. Its broader usefulness quickly became clear in a country that mostly missed out on the credit card era. Features were added and users piled in. It became impossible for regulators and banks not to see the app as a threat.

ImageAnt Group’s headquarters in Hangzhou, China.
Credit…Alex Plavevski/EPA, via Shutterstock

A big test came when Ant began making an offer to Alipay users: Park your money in a section of the app called Yu’ebao, which means “leftover treasure,” and we will pay you more than the low rates fixed by the government at banks.

People could invest as much or as little as they wanted, making them feel like they were putting their pocket change to use. Yu’ebao was a hit, becoming one of the world’s largest money market funds.

The banks were terrified. One commentator for a state broadcaster called the fund a “vampire” and a “parasite.”

Still, “all the main regulators remained unanimous in saying that this was a positive thing for the Chinese financial system,” said Martin Chorzempa, a research fellow at the Peterson Institute for International Economics in Washington.

“If you can’t actually reform the banks,” Mr. Chorzempa said, “you can inject more competition.”

But then came worries about shadowy, unregulated corners of finance and the dangers they posed to the wider economy. Today, Chinese regulators are tightening supervision of financial holding companies, Ant included. Beijing has kept close watch on the financial instruments that small lenders create out of their consumer loans and sell to investors. Such securities help Ant fund some of its lending. But they also amplify the blowup if too many of those loans aren’t repaid.

“Those kinds of derivative products are something the government is really concerned about,” said Tian X. Hou, founder of the research firm TH Data Capital. Given Ant’s size, she said, “the government should be concerned.”

The broader worry for China is about growing levels of household debt. Beijing wants to cultivate a consumer economy, but excessive borrowing could eventually weigh on people’s spending power. The names of two of Alipay’s popular credit functions, Huabei and Jiebei, are jaunty invitations to spend and borrow.

Huang Ling, 22, started using Huabei when she was in high school. At the time, she didn’t qualify for a credit card. With Huabei’s help, she bought a drone, a scooter, a laptop and more.

The credit line made her feel rich. It also made her realize that if she actually wanted to be rich, she had to get busy.

“Living beyond my means forced me to work harder,” Ms. Huang said.

First, she opened a clothing shop in her hometown, Nanchang, in southeastern China. Then she started an advertising company in the inland metropolis of Chongqing. When the business needed cash, she borrowed from Jiebei.

Online shopping became a way to soothe daily anxieties, and Ms. Huang sometimes racked up thousands of dollars in Huabei bills, which only made her even more anxious. When the pandemic slammed her business, she started falling behind on her payments. That cast her into a deep depression.

Finally, early this month, with her parents’ help, she paid off her debts and closed her Huabei and Jiebei accounts. She felt “elated,” she said.

China’s recent troubles with freewheeling online loan platforms have put the government under pressure to protect ordinary borrowers.

Ant is helped by the fact that its business lines up with many of the Chinese leadership’s priorities: encouraging entrepreneurship and financial inclusion, and expanding the middle class. This year, the company helped the eastern city of Hangzhou, where it is based, set up an early version of the government’s app-based system for dictating coronavirus quarantines.

Such coziness is bound to raise hackles overseas. In Washington, Chinese tech companies that are seen as close to the government are radioactive.

In January 2017, Eric Jing, then Ant’s chief executive, said the company aimed to be serving two billion users worldwide within a decade. Shortly after, Ant announced that it was acquiring the money transfer company MoneyGram to increase its U.S. footprint. By the following January, the deal was dead, thwarted by data security concerns.

More recently, top officials in the Trump administration have discussed whether to place Ant Group on the so-called entity list, which prohibits foreign companies from purchasing American products. Officials from the State Department have suggested that an interagency committee, which also includes officials from the departments of defense, commerce and energy, review Ant for the potential entity listing, according to three people familiar with the matter.

Ant does not talk much anymore about expanding in the United States.

Ana Swanson contributed reporting.

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