Contribute Try STAT+ Today

U.S. health officials raised concerns early Tuesday that positive results that AstraZeneca announced Monday for its Covid-19 vaccine may have been based on “an incomplete view of the efficacy data” from a clinical trial and relied on “outdated information,” throwing another curveball in the saga of the company’s vaccine.

In a statement issued soon after midnight Tuesday morning, the National Institute of Allergy and Infectious Diseases said it had been informed about the data questions by the data and safety monitoring board auditing the trial. DSMBs consist of independent medical experts who review data produced from clinical trials.

“We urge the company to work with the DSMB to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible,” NIAID said.

advertisement

In an interview Tuesday morning with STAT, Anthony Fauci, the head of the NIAID, said the DSMB raised concerns because it felt the results in a AstraZeneca press release Monday looked more favorable than more recent data from the vaccine study had shown.

“I was sort of stunned,” Fauci said. “The data and safety monitoring board were concerned that the data that went into the press release by AZ was not the most accurate and up-to-date data. That is what the DSMB communicated to AZ in a rather harsh note. Having seen that letter we could not just let it go unanswered.”

advertisement

Asked why NIAID released its unusual statement, Fauci said, “We just felt we could not remain silent. Because if we did remain silent, we could be understandably accused of covering something up. And we definitely didn’t want to be in that position.”

He added: “In my mind, it’s an unforced error by the company.”

The results released Monday by AstraZeneca came from an interim analysis of a 32,000-volunteer trial through Feb. 17. In a statement Tuesday, the company said it would “immediately engage” with the DSMB “to share our primary analysis with the most up-to-date efficacy data.” The company said it planned to announce results from the primary analysis within 48 hours.

“We have reviewed the preliminary assessment of the primary analysis and the results were consistent with the interim analysis,” the company said. “We are now completing the validation of the statistical analysis.”

The two-paragraph statement from the NIAID opened another chapter in the path of the AstraZeneca vaccine, which was developed along with researchers from the University of Oxford. It came not even 24 hours after the company announced in a press release Monday that its vaccine was 79% effective at preventing symptomatic Covid-19 in a U.S. trial, a result that was better than expected based on earlier trials and appeared to help resolve some questions about the robustness of the vaccine. The company also said the immunization reduced severe Covid-19 and hospitalization by 100%. The results were seen as a final step before the company would apply for authorization from U.S. regulators for its shot, which is already approved in other countries.

The DSMB’s letter, however, said more recent data indicated the vaccine was 69 to 74% effective at preventing symptomatic Covid-19, according to the Washington Post, which obtained a copy of the letter.

“The DSMB is concerned that AstraZeneca chose to use data that was already outdated and potentially misleading in their press release,” the letter says. “The point that is clear to the board is that the [vaccine efficacy number] . . . they chose to release was the most favorable for the study as opposed to the most recent and most complete. Decisions like this are what erode public trust in the scientific process.”

The company’s vaccine had been under scrutiny most recently after European countries paused their rollout last week over safety concerns tied to blood clots, but the European Medicines Agency subsequently said the vaccine’s benefits outweighed its risks and the campaigns restarted.

Based on the trial data released Monday, AstraZeneca said the study identified no new safety concerns. A specific review found no risk of blood clots. The study also did not see a specific type of clot in blood vessels near the brain that the EMA said might be associated with the vaccine. However, this type of clot, called a cerebral venous sinus thrombosis, is so rare it might not be expected to occur in even a large clinical trial.

The NIAID statement Tuesday only cited DSMB concerns about efficacy data, and did not mention safety issues.

The two-dose AstraZeneca vaccine is seen as a great hope to help expand vaccine access around the world because it is less expensive than other Covid-19 vaccines and easier to manufacture and distribute than some others. It is being widely used in Europe and increasingly in Asia.

But the company’s vaccine efforts have been dogged by mishaps and questions about its public announcements. Early on, the U.S. study was stopped for a month-and-a-half because of a neurological condition in one patient that was later determined to be unrelated to the vaccine. In initial trial results announced earlier, the data seemed to suggest at one point that the second dose of the vaccine lowered its efficacy. Some of the earlier confusion stemmed from the company’s unusual strategy of pooling data from clinical trials in its analyses.

The ups and downs with AstraZeneca’s vaccines have increased concerns that the public may turn away from an immunization that could help tame the Covid-19 pandemic, at a time when public health officials are urging people to get inoculated when they have a chance. Fauci said on “Good Morning America” Tuesday the frustration was that “this is very likely a very good vaccine” and that he hoped people would understand the DSMB concerns were an example of one of the many guardrails ensuring the quality of the vaccine development process.

“If you look at it, the data really are quite good, but when they put it into the press release, it wasn’t completely accurate,” Fauci said. “We have to keep essentially trying as hard as we can to get people to understand there are safeguards in place.”

Asked whether he was worried about people’s confidence in the AstraZeneca vaccine and others, Fauci told STAT: “Obviously that’s a concern whenever something like this happens, that it could erode public trust, yes.”

But he stressed that the FDA, when it reviews AstraZeneca’s vaccine for authorization, will make an independent decision.

Helen Branswell and Matthew Herper contributed reporting. 

This story has been updated with comments from AstraZeneca and Anthony Fauci. 

Correction: This story previously misstated the reason for the pause of AstraZeneca’s U.S. clinical trial. 

  • The European Medicine Agency on Thursday determined the benefits outweighed the risk, so I think most countries in the EU are resuming vaccinations. There have been some blood clots in 13 people, most women under 35, and I think they determined the cause and how to treat them.
    The pandemic is still a serious problem.
    The US could delay or even reject the AstraZeneca vaccine but it would delay getting a large proportion of the population vaccinated.
    I think the US is sending millions of doses of the vaccine to Canada and Mexico, 1.5 to Canada and 2.5 to Mexico, apparently saying they will “loan” the vaccinations.

  • I don’t think I agree with Fauci’s approach on this. This should have been done and amended privately as the difference is neither clinically nor statistically significant. It’s about choice a study to present, not necessarily falsification of data results.

  • My daughter got the AZ flu mist fall 2015, and died from the flu April 2016. We later found out their flu mist vaccine was so ineffective that it provided zero protection. I will never trust that company’s vaccines again.

  • To me, it looks like this vaccine is not going to be a big part of the US fight against our epidemic – maybe it will be good against the pandemic, but not our piece of it.
    Requiring two doses, it is only easier in the sense that no super cold freezers are needed. That may not be trivial but it has not been the chokepoint in our vaccine efforts, as best I can tell.
    Additionally, this vaccine, at least the current design, seems to have very low efficacy against South African variant and maybe New York and other variants with the E484 mutation.
    With the US up to 2.5M doses/day now (we are told) and over 2/3 of people over 65 partly vaccinated already, we are on track to win the race against the UK variant, B1117, without help from AZ.
    If AZ was effective against South African and New York variants, it would be very good to have it, but the South African trials indicate it will not help us stop the variant epidemic which seems to be coming this summer in the US, unless the vaccines we are using are significantly more effective.

    • I wanted to add – will someone please, please, please ask Dr. Fauci and Biden et al, what they are doing to actually TEST the efficacy of all our vaccines against the variants we know of, what the numbers are for the variants, and the expected growth rates, and how soon we can get updated vaccines which are proven to stop them? I realize not all this information is going to be provided, or is even known, but it seems quite important and seems to be neglected.

  • AZ is the only one so far that has gotten caught. They aren’t the only ones. Remember, many of these companies have been found guilty of many other falsifications or withholding of information on other pharmaceuticals. Think Vioxx and the opioid epidemic. Many of these companies see this as a way to restore confidence in them as vaccine heroes.

    • Vanessa,
      You aren’t wrong, bad apples do exist in pharma/biotech. However, to consider the industry as one group is misleading and erodes trust in thousands of products that cure and treat a multitude of problems. Most of the people who have dedicated their lives to advancing science have good intentions. They don’t get press coverage.
      To use opioids as an example of an anti-pharma statement is also misleading. The blame for the opioid epidemic falls on industry, our healthcare system (doctors, pharmacies, PBMS, insurers) and ourselves. It took a village to fuel an epidemic.
      I personally thought Vioxx should have been kept on the market. It worked. Patients should be able to make decisions about their risk tolerance.
      M.P.

  • If you use this vaccine in America many people will reject it. It doesn’t feel safe to a lot of us. Stay with the ones you know are safer.

    • fAZ is the only one so far that has gotten caught. They aren’t the only ones. Remember, many of these companies have been found guilty of many other falsifications or withholding of information on other pharmaceuticals. Think Vioxx and the opioid epidemic. Many of these companies see this as a way to restore confidence in them as vaccine heroes.

  • I wonder how many people died because Fauci and the FDA slow rolled the AZ vaccine?

    The arrogance of the FDA is quite astonishing!!!

    • The FDA slow-rolled nothing.

      The FDA does not initiate the issuance of an EUA. The company must submit an EUA request for review and approval by the FDA. AstraZeneca has not done so. They did not do so because their UK/Brazil trial and analysis didn’t meet FDA standards.

      As far as the arrogance of the FDA and our rigid approval procedures, look up “thalidomide”.

    • Whaaaat? What planet are you living on? AZ FALSIFIED INFORMATION, and you want it fast-tracked? You sound like a troll.

  • I am 74 and 6 months. I just got one shot, first dose and with What has happened recently in France and in others countries in U.E. I am afraid of having a second dose. Please be kind enough to let me know about the USA ‘ investigations ! Thanks in advance !

    • Get the second shot. There’s no indication that the AstraZeneca vaccine is unsafe. It may not protect as well as some of the other vaccines, but it will protect much, much better than having no vaccine at all. But you need the second shot.

    • Start over! Forget about the second dose of AZ. Too risky. Get two doses of Pfizer or Moderna. Or one dose of J&J. The same way one who had COVID and would still benefit from the vaccine, the same way the immunology bump from AZ (if there is any) would not interfere with the vaccine (from the other three sources).

  • How convenient for AstraZeneca to be allowed to continuously revise its statements and not be able to run a rigorous study – remember the post hoc, half-concentration result blamed on a ‘manufacturing error’? If they get so much support from the politicians, let the politicians take their vaccine. If AstraZeneca cannot get a story right, how could they be trusted with a health issue?

  • Above: “a cerebral hemorrhage in one patient that was later determined to be unrelated to the vaccine” … Stat Oct 23 2020: “We as a company have found no evidence the vaccine candidate caused the event”. Determined is different from considered.

    • True. Not finding evidence often means an insincere effort to find that evidence, especially if the company doing the investigation would be harmed if that evidence were found. It doesn’t mean the evidence doesn’t exist. It’s not proof. AZ now appears to have been caught fudging the numbers. It appears that this vaccine has serious problems on multiple fronts, and AZ is scrambling to salvage it’s share of the COVID vaccine gravy train.

Comments are closed.