Clinical trial results released this week by British pharma giant AstraZeneca reported that its vaccine is safe and effective, yet the data raised fresh concerns around a vaccine poised to play a major role in quelling the COVID-19 pandemic.
The company announced results from a trial of more than 32,000 volunteers from St. Louis to San Diego to Santiago, Chile. But an independent scientific team tasked with reviewing the data told AstraZeneca and the U.S. government that it had concerns with how those results were reported.
The confusion has clouded what otherwise appears to be a good vaccine, according to Dr. Davey Smith, director of infectious disease research at the University of California, San Diego.
"It just turned into a very messy situation," Smith said. "And when we're trying to convince people that a vaccine is good or safe, (or) find out if it's good or safe or not, then that messiness doesn't help."
On Monday, the company shared in a press release that its vaccine was 79% effective in preventing participants from getting sick with COVID-19, and 100% effective at preventing hospitalization and death.
The news was celebrated by researchers and public health officials, who hoped the results would speed the vaccine's approval in additional countries. The vaccine has been cleared for use throughout Europe, the U.K., India, Canada and Mexico, and AstraZeneca has said it can manufacture 3 billion doses by the end of 2021.
But later that night, the data safety monitoring board, an independent team of experts tapped to review ongoing trial data, expressed concerns that AstraZeneca had reported outdated results in its press release.
The company issued an updated press release Thursday saying its vaccine was 76% effective — a small drop from its initial figure, and one that may not be statistically significant. But the mixed messaging was a red flag to Shane Crotty of La Jolla Immunology in La Jolla, California.
"They've had problems all along with analyzing their data well and running good clinical trials," Crotty said.
Those problems date back to September, when AstraZeneca paused its trial to investigate whether a volunteer who showed symptoms of spinal inflammation became sick because of the vaccine. The trial's monitoring board didn't find evidence the illness was linked to the vaccine, but the company drew criticism when its CEO shared details of the participant's symptoms in a call with investors rather than with the public.
And in late November, the company reported that, due to an error, it had tested two different dosing strategies for its vaccine in the U.K. and Brazil. Some participants received two full doses while a smaller group received a half-dose for their first shot and a full dose for their second. Data from the former group showed a vaccine efficacy of 62% compared to 90% for the half-dose, full dose group.
AstraZeneca reported an overall effectiveness of 70%, which rankled researchers concerned by the company combining data from different trials. Another issue: Those who received a half dose for their first shot were below 55 years old, making it possible that the dosing strategy seemed more effective because it was tested on people who were younger and healthier.
Those miscues haven't changed Crotty's overall sense that the vaccine is safe and effective. Neither have reports in Europe of a few people who received the vaccine later developing blood clots. The European Medicines Agency recently investigated the matter and said it didn't see a clear link between the small number of cases and the vaccine.
But Crotty still wouldn't recommend the AstraZeneca vaccine to anyone with access to shots from Johnson & Johnson, Moderna or Pfizer — the three vaccines currently in the U.S.
"It's not that I couldn't recommend it," he said. "But I wouldn't."
A major reason is the emergence of new, faster-spreading coronavirus variants. A study posted in February showed that AstraZeneca's COVID-19 vaccine was 21% effective in a group of 2,000 South Africans — and just 10% effective against the fast-spreading viral strain first found in that nation. By comparison, Johnson & Johnson's vaccine was 57% effective in South Africa.
Crotty says the AstraZeneca vaccine can still be useful in the race against viral variants, however, noting that it works well against a strain first spotted in the U.K. and that it's still essential to take whatever vaccine is available to you. Both he and Smith are looking forward to seeing the data the company submitted to the Food and Drug Administration, which will provide a fuller picture of the vaccine's safety and efficacy.
"I'd want to really see that data," Smith said. "This is where we really need to rely on the regulatory agencies to look at the full data set."
