- AstraZeneca released details of its latest clinical trial results, but a U.S. safety board raised concerns that the data may be “outdated.”
- Results published on March 22 were based on an interim analysis of data from the phase 3 clinical trial, which included more than 32,000 participants in the United States, Chile, and Peru.
- AstraZeneca released another statement on March 23 saying that it will work with the safety board to review the current data and release the results of its analysis within 48 hours.
The COVID-19 vaccine developed by AstraZeneca and the University of Oxford had an efficacy rate of 79 percent against symptomatic disease and 100 percent against severe disease and hospitalization in a new clinical trial, the company said Monday.
“Seventy-nine percent efficacy against symptomatic disease is very good,” said Dr. Sarah George, associate professor of infectious diseases at Saint Louis University School of Medicine. “There were also no cases of severe disease in the vaccinated group, so that’s good.”
These results are based on an interim analysis of data from the drugmaker's phase 3 clinical trial, which included more than 32,000 participants in the United States, Chile, and Peru.
At the time of the analysis, 141 trial participants had developed symptomatic COVID-19, with most of the cases occurring in people who received an inactive placebo.
The results were announced in a press release, so the details are sparse.
Since then, an independent U.S. safety board overseeing the vaccine trial has raised concerns about the information released by AstraZeneca.
Safety board raises concerns about data
The Data and Safety Monitoring Board (DSMB) is concerned that the company may have included “outdated information” that could give an “incomplete view” of the vaccine’s efficacy, according to a statement released early March 23 by the National Institute of Allergy and Infectious Diseases (NIAID).
The NIAID urged AstraZeneca to work with the DSMB to review the data, and make sure the “most accurate, up-to-date efficacy data” is shared with the public as soon as possible.
AstraZeneca released another statement saying that it will work with the DSMB to review the current data and release the results of its analysis within 48 hours.
Dr. Anthony Fauci, the head of the NIAID, said on “Good Morning America” that what happened was unfortunate, calling it an “unforced error” by the company.
“The data are really quite good,” Fauci said, “but when [the company] put it into the press release, it wasn’t completely accurate.”
On Twitter, Saad B. Omer, PhD, director of the Yale Institute for Global Health, raised a common concern among clinical trial scientists about this type of public announcement by companies.
“Say it with me: data sharing through press release (without any additional material e.g. a slide set, preprint etc.) is not a good idea,” he wrote.
Fauci added that the vaccine review process includes many safeguards — including the DSMB — that ensure that vaccines approved by the Food and Drug Administration (FDA) are safe and effective.
The Washington Post obtained a letter that the DSMB sent to AstraZeneca and the NIAID.
The letter states that data seen by the safety board as late as March showed that the vaccine had an overall efficacy of 69 to 74 percent. The board “strongly recommended” that the company include this information in its press release.
AstraZeneca said it plans to submit an application for emergency approval to the FDA in the coming weeks.
FDA scientists will then review the company’s data in depth and present its analysis to the advisory committee that has reviewed the other COVID-19 vaccine applications.
The company said it will also submit its full analysis to a peer-reviewed journal for publication.
Study found no blood clotting concerns
AstraZeneca’s COVID-19 vaccine has been under scrutiny recently after several European countries temporarily halted its rollout after reports of blood clotting in some people who had received the vaccine.
Following an emergency investigation, the European Medicines Agency (EMA) said on March 18 that the vaccine’s benefits outweigh the risks, and concluded that the vaccine is “not associated with an increase in the overall risk of blood clots, or thromboembolic events.”
However, the agency said “the vaccine may be associated with very rare cases of blood clots.” The agency will continue to watch for any connection between the vaccine and blood clotting disorders.
Germany, France, Italy, and Spain have since said they would resume the rollout of the AstraZeneca vaccine, reports BBC News.
In response to these concerns, the DSMB and an independent neurologist carried out a more specific review of the new clinical trial data, looking for blood clotting events, including a type of brain clot called a cerebral venous sinus thrombosis.
They found no increased risk of blood clotting among the more than 21,000 trial participants who had received at least one dose of the vaccine.
Certain rare events, though, may not show up during a clinical trial. This is why the FDA and the Centers for Disease Control and Prevention (CDC) continue to monitor the safety of vaccines after they're released.
In its press release, AstraZeneca said the vaccine was “well tolerated” by people who received it, and “no safety concerns related to the vaccine” were identified by the DSMB.
Of the participants included in the interim analysis, about 79 percent were white, 22 percent were Hispanic, 8 percent were Black, 4 percent were Native American, and 4 percent were Asian.
Around 20 percent of people in the trial were 65 years or older, and about 60 percent had health conditions linked to a higher risk of severe COVID-19, such as diabetes, severe obesity, or heart disease.
Overall efficacy for participants 65 years or older was 80 percent, AstraZeneca said.
This is welcome news. Some countries that approved the AstraZeneca vaccine had initially excluded older adults from vaccination due to a lack of data on this age group in earlier trials.
Although AstraZeneca’s overall efficacy is lower than that of the Pfizer-BioNTech and Moderna vaccines, it compares favorably in terms of protecting against severe disease and hospitalization.
However, it’s difficult to directly compare the vaccines, because the clinical trials used different criteria for how to measure the outcome.
The studies were also done in different countries at different times, and with different SARS-CoV-2 variants circulating.
As part of the AstraZeneca trial, adults of all ages received either two doses of the vaccine given 4 weeks apart, or an inactive placebo given at the same interval.
The results of a previous trial, published in The Lancet, suggest that waiting up to 12 weeks before giving the second dose may boost the vaccine’s efficacy.
Vaccine may help lower-income countries most
The AstraZeneca vaccine has already been approved in more than 70 countries, the company said.
If the FDA approves the vaccine, it will bring the number of approved vaccines in the United States to four.
However, “we’re going to have millions more doses of the three licensed [vaccines] in the United States by the spring,” George said. “So by the time [the AstraZeneca vaccine] does go through the FDA approval process, there may not be as much use for it in this country.”
The vaccine can still help other countries vaccinate their population, especially those that have been largely shut out of access to COVID-19 vaccines.
Higher-income countries such as the United States make up just a fifth of the global adult population, but they have purchased more than half of all vaccine doses, reports the Kaiser Family Foundation.
The United States has already agreed to send 4 million doses of the AstraZeneca vaccine that it's not using to Canada and Mexico.
The AstraZeneca vaccine’s less rigorous storage requirements will make it easier to distribute in areas of the world without reliable access to freezer storage. It can be stored at normal refrigerator temperatures for at least 6 months.
“Cold-chain monitoring, as it is called, is a real issue with vaccines,” said George, “particularly in parts of the world where electricity supplies are minimal or not reliable.”
Both the Pfizer-BioNTech and Moderna vaccines need to be stored in a freezer until they're thawed before use.
Because of the vaccine’s easier handling, Dr. Peter Hotez, dean for the National School for Tropical Medicine at the Baylor College of Medicine, told CNN that it “is one of our workhorse vaccines that we're expecting for Africa and Latin America.”