March 25, 2021. This story has been updated to include revised vaccine efficacy based on additional data analyzed by AstraZeneca.
In an unusual move, on March 23 the U.S. National Institute of Allergy and Infectious Diseases (NIAID) issued a strongly worded statement asking AstraZeneca to “ensure the most accurate, up-to-date efficacy data be made public as quickly as possible.”
On March 22, AstraZeneca released the results of its long-awaited U.S. trial of its COVID-19 vaccine, developed with scientists from Oxford University’s Jenner Institute. The data showed that the two-dose vaccine was 79% efficacious in protecting people from symptoms of COVID-19, and 100% efficacious in protecting against severe disease.
Several days later, however, the company issued another press release including additional data that showed the vaccine is 76% efficacious in protecting people from disease.
The original data may not have included the most updated information that the independent Data Safety Monitoring Board (DSMB), which reviews U.S. vaccine studies, had shared with the company. U.S. trials of COVID-19 vaccines are conducted under randomized, double blind conditions, which means neither the doctors and staff running the trials nor the participants volunteering in them know whether they are receiving the actual vaccine being tested, or a placebo. Only the DSMB has the authority to unblind the data to determine both efficacy and reveal any safety concerns. The DSMB does periodic unblinding checks to see, for example, if side effects are occurring at higher rates in the vaccinated versus placebo groups. The DSMB also determines if enough cases of COVID-19 have accumulated to provide the statistical power necessary to determine whether a vaccine works.
In all of the U.S. COVID-19 vaccine trials, the same DSMB, made up of about a dozen independent experts, is overseeing data from different vaccine makers, to ensure that the same standards are being used to review the data and that the final results are consistent.
During the evening on March 22, the DSMB grew concerned by the data included in AstraZeneca’s press release, covered extensively by the media, reporting the study results. The board wrote letters to Dr. Anthony Fauci, director of NIAID, who serves as the U.S. government representative for the vaccine trials, as well as the Biomedical Advanced Research and Development Authority, which helped to fund the trial, and AstraZeneca expressing its concern that the company chose to include only older data in its release, which “may have provided an incomplete view of the efficacy data,” NIAID said in a statement.
“The more recent data did not make the data look as good—it wasn’t bad, but it wasn’t as good,” says Fauci. “What concerned the DSMB was that at the time the press release went out, the DSMB knew the company had more recent data, and they chose to report the earlier data which made the data look a little better, that’s what the DSMB is saying.”
In a statement responding to the DSMB’s concern, AstraZeneca said 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. We intend to issue results of the primary analysis within 48 hours.”
On March 25, the company issued another release with the additional data involving 49 more cases of COVID-19. Taking those into account, the vaccine’s efficacy was 76%; the shot remained 100% efficacious in protecting people from severe disease. The company said it provided the revised data to the DSMB, and would use that data as part of its request to the U.S. Food and Drug Administration (FDA) for emergency use authorization.
This is only the latest bump on AstraZeneca’s road to an authorized vaccine in the U.S.. After small numbers of unusual, serious illnesses were reported among study volunteers, the trial was halted in the U.S. and elsewhere last fall; the study was delayed by a month while regulators reviewed the report in the U.S. After the vaccine was authorized in the U.K. and the European Union, concerns about blood clots among people who have been vaccinated emerged in mid-March, prompting a number of countries to halt using the shot until the European Medicines Agency reviewed those cases and determined on March 18 that the benefits of the vaccine still outweighed any risk. AstraZeneca’s U.S. trial also showed that the rate of blood clots among people in the study weren’t any higher than would be expected in that population even if they hadn’t been vaccinated.
In another blow to the vaccine, on March 16 South African researchers reported in a study published in the New England Journal of Medicine that the two-dose regimen was only about 10% efficacious in protecting people from COVID-19 if they were infected with a new variant of the virus known as B.1.351, which was first reported in South Africa and starting to account for more cases around the world.
The company’s decision to report the “outdated” data could further erode confidence in the vaccine, says Fauci. “I look upon this as an unforced error, really,” he says. “There was no need for this to happen.”
It could also raise questions for the FDA scientists who will review AstraZeneca’s request for emergency use authorization, which the company plans to submit in coming weeks with the additional data. “At the end of the day, the FDA gets all the data and they do a completely independent analysis of all the data,”’ says Fauci. “No matter what went on ahead of time, at the end of the day, the truth will come out.”
AstraZeneca has committed to providing 3 billion doses of its vaccine by the end of 2021, much of it through COVAX, the global vaccine initiative that is procuring and distributing vaccines to lower resource countries.