뉴욕타임즈(2021-3-23): 미국 보건 당국 관계자, 아스트라 백신 실험결과에 의문제기

[나가자]

미국 보건 당국 관계자, 아스트라 백신 실험결과에 의문제기

https://www.nytimes.com/2021/03/23/business/astrazeneca-vaccine-questions.html?searchResultPosition=2

U.S. Health Officials Question AstraZeneca Vaccine Trial Results

미국 보건 당국 관계자, 아스트라 백신 실험결과에 의문제기

According to federal officials, an independent panel of medical experts said the encouraging results announced on Monday might have relied on outdated information.

Health care professionals preparing doses of the AstraZeneca vaccine in Milan on Monday.Credit...Alessandro Grassani for The New York Times

By Rebecca Robbins, Noah Weiland, Sharon LaFraniere and Benjamin Mueller

Published March 23, 2021 Updated March 25, 2021

Only hours after AstraZeneca announced encouraging news about the effectiveness of its Covid-19 vaccine on Monday, a group of medical experts charged with monitoring the company’s clinical trial made a highly unusual accusation: AstraZeneca had essentially cherry-picked data to make its vaccine look better.

The accusation, in a two-page letter sent Monday to the company and federal officials, was a fresh blow to the credibility of a vaccine whose low price and relatively easy storage have made it critical to the global fight against the coronavirus pandemic.

The private letter, which was described by people who have read it, castigated AstraZeneca for jeopardizing the integrity of a closely watched clinical trial.

“Decisions like this are what erode public trust in the scientific process,” the oversight board wrote.

The letter prompted the National Institute of Allergy and Infectious Diseases to issue a sharply worded statement on Tuesday shortly after midnight, disclosing the panel’s concerns.

The fight is about the degree of effectiveness of a vaccine that is undisputably effective.

While AstraZeneca said on Monday that its vaccine appeared to be 79 percent effective at preventing Covid-19, the panel of independent experts said the actual number may have been between 69 percent and 74 percent. The mass availability of a vaccine with even a 69 percent efficacy rate could help the world conquer the coronavirus.

But the public airing of a conflict between a pharmaceutical company and a board overseeing a clinical trial is almost unheard-of. It is certain to trigger extra scrutiny of the vaccine by the Food and Drug Administration and other regulators if, as expected, AstraZeneca seeks their authorization to use it on an emergency basis in the United States.

Repeated problems with the data presented by AstraZeneca have shattered the confidence of American regulators and threaten to cast a worldwide cloud over the company’s vaccine.

“Any type of thing like this could unfortunately contribute to a lack of confidence in the process,” said Dr. Anthony S. Fauci, the nation’s leading infectious-disease expert.

Fears that the vaccine might trigger rare but serious side effects had led more than a dozen countries, mostly in Europe, to temporarily suspend the use of the shot. European regulators last week affirmed the vaccine’s safety. The results from the U.S. trial on Monday — providing the cleanest, most complete picture of the vaccine’s efficacy — seemed to validate the vaccine’s safety and made it look more effective than in earlier trials.

In short, it bolstered the credibility of arguably the world’s most important vaccine, one that has been authorized for use in more than 70 countries. But the overnight announcement from the institute immediately raised a new set of questions about it and AstraZeneca.

“If they keep making these unforced errors, then that’s going to derail confidence, and that will really affect our ability to combat this pandemic,” said Dr. Peter J. Hotez, a vaccine expert at the Baylor College of Medicine.

At issue is whether to count, in the public release of data, more recently confirmed cases of Covid-19 among participants. The oversight board pushed AstraZeneca representatives last week to go through a backlog of potential cases and classify whether they were or were not Covid-19. That had the potential to affect the vaccine’s effectiveness rate, for better or worse.

The requested analysis showed that the vaccine was between 69 percent and 74 percent effective, according to the oversight board’s letter.

But when AstraZeneca unveiled its interim results on Monday, the company did not count those newly classified Covid-19 cases. As a result, it reported that the vaccine appeared to be 79 percent effective at preventing the disease.

Until they received the monitoring board’s letter, AstraZeneca executives weren’t aware that the panel expected them to include the updated figures in their news release, according to a person familiar with the executives’ thinking.

Federal officials, however, were stunned to discover on Monday that AstraZeneca had released those results even though the monitoring board had spent days pushing for — and eventually received — updated data. By then, Dr. Fauci had publicly hailed the results at a White House briefing, and the company had been showered with positive media coverage. AstraZeneca’s shares rose about 4 percent on Monday.

AstraZeneca on Tuesday defended its actions, saying the interim results appeared to be “consistent” with more recent data collected during the trial. The company said it would immediately share its latest data with the monitoring board and reissue fuller results within 48 hours.

The company’s shares fell 3.5 percent on Tuesday.

Dr. H. Cody Meissner, an infectious-disease expert at Tufts University School of Medicine, said he had never before seen such a sequence of events with a vaccine developer. “You know the anti-vaccine community is going to use this as fodder to argue that pharmaceutical companies are always deceptive,” he said.

Dr. Meissner, who serves on a board that advises the F.D.A. on whether to approve vaccines, predicted that if AstraZeneca sought such authorization, board members would be even more careful than usual to scrutinize its hundreds of pages of data.

“I will make sure I don’t skip a word,” he said.

Dr. Eric Topol, a clinical trials expert at Scripps Research in San Diego, said it was “highly irregular” to see such a public display of friction between a monitoring board and a pharmaceutical company.

“I’ve never seen anything like this,” he said. “It’s so, so troubling.”

AstraZeneca’s relationship with the U.S. authorities has been fraught almost since it began its clinical trial here last summer. Senior health officials complained that the company was not being forthright about the design of its clinical trials, its results and safety issues.

Last week, an apparent delay in the release of the vaccine’s interim trial results raised fresh suspicions among federal officials.

In response to questions from The New York Times, an AstraZeneca spokeswoman, whom the company refused to name, said on Friday that any back and forth between the company and the monitoring board was simply run-of-the-mill dialogue.

“As is often the case,” she said, monitoring boards “can request new or clarifying analyses of data from the trial. This would enable them to ensure the robustness of their determinations.”

With more than 32,000 participants, the U.S. trial, which received funding from the National Institutes of Health, was the largest test of its kind for the shot. The results that AstraZeneca released on Monday reflected an interim look at the data after 141 Covid-19 cases turned up among volunteers, one-third of whom had received a saline placebo. That was enough cases to eval‎uate whether the vaccine was effective at preventing the disease.

The implications of the trial extend beyond the United States, which has ordered 300 million doses of the vaccine.

AstraZeneca’s application for emergency authorization may take more time to review than those from the companies that have already won clearance. If there is not an obvious need for the vaccine in the United States by the time the F.D.A. eval‎uates it, regulators may feel less urgency to complete their review.

The results on Monday had the potential to ease concerns in Europe and other parts of the world that are counting on hundreds of millions of affordable, durable doses of the AstraZeneca vaccine. Regulators in Europe said last week that the shot was “safe and effective,” having conducted a review after a small number of people who had recently been inoculated developed blood clots and abnormal bleeding. The U.S. trial did not turn up any sign of such problems.

Many millions of people have received the AstraZeneca shot worldwide, including more than 17 million in Britain and the European Union, almost all without serious side effects. In an effort to increase public confidence, many European political leaders have gotten the injections in recent days. The AstraZeneca vaccine has also been administered in the past week to leaders in South Korea, Taiwan and Thailand.

“When you get the call, get the jab,” the British health secretary, Matt Hancock, urged on Monday. More than 11 million AstraZeneca doses have been administered in Britain, almost all of them without serious side effects, and the vaccination campaign has reduced hospitalizations and helped the country to emerge from a dreadful wintertime wave of infections.

Even if AstraZeneca persuades American regulators to authorize its vaccine, it is not clear whether the Biden administration will deploy it here. By the end of May, federal officials have said, the three already authorized sets of manufacturers — Pfizer and BioNTech, Moderna, and Johnson & Johnson — will have supplied enough doses to cover all American adults.

The dust-up over the U.S. data is the latest in a series of miscues and communication blunders by AstraZeneca, whose vaccine, developed with the University of Oxford, was once a front-runner in the race for a safe and effective inoculation.

In September, key federal officials, including the F.D.A.’s commissioner at the time, Dr. Stephen Hahn, learned only from the news media that trials of the vaccine were halted globally after a volunteer in Britain developed worrisome neurological symptoms. AstraZeneca officials had been on a conference call with the F.D.A. just a few hours before the news broke, but they neglected to mention the safety issue.

The U.S. trial was paused for nearly seven weeks last fall, in part because AstraZeneca was slow to provide the F.D.A. with evidence that the vaccine had not caused the neurological symptoms. Investigators concluded that the symptoms could not be linked to the vaccine.

Still, the delay left AstraZeneca trailing the three authorized manufacturers.

.......................................................................

Sheryl Gay Stolberg and Sheila Kaplan contributed reporting.

Rebecca Robbins joined The Times in 2020 as a business reporter focused on covering Covid-19 vaccines. She has been reporting on health and medicine since 2015. @RebeccaDRobbins

Noah Weiland is a reporter in the Washington bureau, covering health care. He was raised in East Lansing, Mich., and graduated from the University of Chicago. @noahweiland

Sharon LaFraniere is an investigative reporter. She was part of a team that won a Pulitzer Prize in 2018 for national reporting on Donald Trump’s connections with Russia. @SharonLNYT

Benjamin Mueller is a United Kingdom correspondent for The New York Times. Before that, he had been a police and law enforcement reporter on the Metro desk since 2014. @benjmueller

https://www.nytimes.com/2021/03/23/business/astrazeneca-vaccine-questions.html?searchResultPosition=2 

[나가자]

AstraZeneca had essentially cherry-picked data to make its vaccine look better.
아스트라제네카 사는 자신의 백신이 더 좋게보이도록 선별된 데이타를 사용했다.