The National Institute of Allergy and Infectious Diseases (NIAID) in a statement issued early Tuesday said AstraZeneca may have released "outdated information" on its Covid-19 vaccine that "may have provided an incomplete view" of the vaccine's effectiveness.

In response, AstraZeneca issued a statement saying the numbers "were based on a pre-specified interim analysis" and that it would "immediately engage with the independent Data Safety Monitoring Board (DSMB) to share our primary analysis with the most up to date efficacy data."

Health officials raise concerns about AstraZeneca's Covid-19 vaccine data

In a press release issued Monday, AstraZeneca announced preliminary data from a large-scale clinical trial designed to test its vaccine's safety and effectiveness. According to the release, the trial involved 32,449 participants who received either two shots of the vaccine candidate—which AstraZeneca developed with the University of Oxford—or two saline shots administered four weeks apart.

The vaccine was found to be 79% effective in preventing symptomatic cases of Covid-19, and no severe cases or hospitalizations occurred among the participants who had received the vaccine, according to the release.

However, NIAID after midnight on Tuesday morning issued a statement raising questions about the data released by AstraZeneca. NIAID in its statement said the DSMB—an independent panel of experts responsible for overseeing the trial under NIH—had notified AstraZeneca, the Biomedical Advanced Research and Development Authority, and NIAID that it was "concerned" by the initial trial data AstraZeneca had released on its Covid-19 vaccine.

"The DSMB expressed concern that AstraZeneca may have included outdated information from that trial, which may have provided an incomplete view of the efficacy data," NIAID said.

NIAID in the statement urged AstraZeneca "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."

According to the New York Times, companies sponsoring clinical trials for drugs or vaccines typically wait for a monitoring board to conduct analyses and draw conclusions before releasing trial data. The DSMB's analysis of AstraZeneca's trial recently had been delayed several times as the board requested revised reports from those involved with handling the company's trial data, a person familiar with the matter who was not authorized to discuss it publicly told the Times. The DSMB eventually communicated the results of the trial to AstraZeneca in a meeting over the weekend, which set the stage for the company's announcement on Monday, the Times reports.

In a statement released on Tuesday morning, AstraZeneca said, "The numbers published yesterday were based on a pre-specified interim analysis with a data cut-off of 17 February. We have reviewed the preliminary assessment of the primary analysis and the results were consistent with the interim analysis. We are now completing the validation of the statistical analysis."

The company added, "We will immediately engage with the independent [DSMB] to share our primary analysis with the most up to date efficacy data. We intend to issue results of the primary analysis within 48 hours."

Reactions

Many observers noted the unusual nature of NIAID's statement and the discord between the DSMB and AstraZeneca.

"DSMB externalizations of concerns are deeply unusual for multinational pharma companies and suggest an extraordinary high level of friction between the DSMB and the sponsor," Citi analysts said in a note.

Similarly, Eric Topol, director of the Scripps Research Translational Institute, said it was "highly irregular" to see a monitoring board and clinical trial sponsor publicly disagree because they are typically in close agreement. "I've never seen anything like this," he said. "It's so, so troubling."

However, Stephen Evans, a pharmacoepidemiology professor at London School of Hygiene & Tropical Medicine, said the DSMB's request for more up-to-date data may stem from the recent spread of new variants of the novel coronavirus, which may be less susceptible to Covid-19 vaccines than earlier variants of the virus.

Health officials' concerns represent new setback for AstraZeneca

The NIAID's statement represents the latest setback for AstraZeneca's Covid-19 vaccine, Bloomberg reports. Last year, AstraZeneca faced questions after it announced data from a trial in which one group of trial participants accidentally received a lower-than-intended first dose of the vaccine, according to Bloomberg, leading to confusion about whether different dosages actually drove significantly different immune responses.

More recently, numerous countries last week suspended the use of the vaccine due to a small number of reports of blood clots among those who had received the inoculation. However, the European Union's drug regulator, called the European Medicines Agency, and the World Health Organization have said there is little reason to believe the vaccine caused the blood clots, which can occur by chance in otherwise healthy populations. Several countries have since resumed administering the vaccine.

"The last thing this vaccine needs is more concern when we kind of thought we were at that point now where we'd put to bed all the other concerns," said Paul Griffin, an associate professor of medicine at the University of Queensland in Brisbane, who is conducting clinical studies in Australia on four Covid-19 vaccine candidates.

"This is indeed an extraordinary act. The negative reports about this vaccine do not stop, although my assessment is that it is well tolerated and safe, but clearly less effective than the two mRNA vaccines" developed by Pfizer/BioNTech and Moderna, Peter Kremsner of the University Hospital in Tuebingen, Germany, said.

AstraZeneca on Monday said it's preparing to seek an emergency use authorization from FDA for its vaccine candidate "in the coming weeks." However, observers have said the DSMB's concerns may delay the vaccine's authorization (Robbins/Kaplan, New York Times, 3/23; Kim/Copley, Reuters, 3/23; Associated Press, 3/23; Cortez et al., Bloomberg, 3/23; AstraZeneca press release, 3/23; Kim/Copley, Reuters/Brainerd Dispatch, 3/23).