March 23, 2021 -- Officials at the National Institute of Allergy and Infectious Diseases, the agency run by Anthony Fauci, MD, issued a statement overnight calling into question the completeness of COVID-19 vaccine data that AstraZeneca shared in its interim phase III efficacy and safety findings.
Reactions from experts were swift. Some support NIAID's concerns and want answers from the company, while others see this as a minor issue for a company plagued with controversy at almost every step of its vaccine development.
The NIAID statement says that when announcing phase III interim results on Monday, the company may have shared outdated information that "may have provided an incomplete view of the efficacy data."
The questions originated from members of the data and safety monitoring board (DSMB) tasked with reviewing the clinical trial. The DSMB specifically criticized the company for "cherry picking" a more favorable overall efficacy number, 79%, while more recent data reviewed by the board put the vaccine efficacy between 69% and 74%, according to multiple media reports. To learn more about clinical trials, click here.
"What happened is the company put out a press release giving data and making some conclusions about the efficacy," Fauci said on Good Morning America on Tuesday. "The data and safety monitoring board, when they saw that press release, they got concerned and wrote a rather harsh note to them and with a copy to me."
The letter, he said, explained "they felt that the data that was in the press release were somewhat outdated and might, in fact, be misleading a bit, and wanted them to straighten it out."
The Company Response
AstraZeneca officials responded Tuesday and said the interim results were collected up to Feb. 17 as planned. In addition, the company "will 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," the company said in a statement.
In the meantime, experts have questioned both AstraZeneca’s actions as well as the NIAID statement. "The situation is shocking. I've never seen a statement like that before," Hilda Bastian, PhD, a clinical trials expert and one of the founders of the Cochrane Collaboration, told Medscape.
"It's very hard to understand what happened here. The trial protocol says the DSMB ’will facilitate the interim analysis‘, so if everything was done as it should have been, the DSMB wouldn't be blindsided by a company press release," she said. "If doing the press release this particular way was a PR exercise, then it's backfired badly."
“It is not unknown for a DSMB to disagree with investigators over interpretation of trial results," Stephen Evans, professor of Pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, said. However, he added, "It is usually done in private, so this is unprecedented in my opinion."
Other experts criticized the NIAID statement for being vague. For example, the agency says in part: ”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.”
“I find this problematic in various ways. It reads like a sentence from the conclusions of a paper; but one that has been presented out of context, without any explanation of the reasons for drawing the conclusion, or of what they think the consequences might be," Peter English, MD, retired consultant in communicable disease Control and immediate past chair of the British Medical Association Public Health Medicine Committee, said.
“In my opinion this is shamefully bad communication by NIH as with their lack of clarity they have left room for speculation which could be damaging for vaccine uptake," English added.
“For me, this further announcement by the DSMB in response to the AZ release yesterday highlights the importance of data being provided at the same time as summaries being made public," Stephen Griffin, PhD, associate professor in the School of Medicine at the University of Leeds, said.
"Naturally, the news yesterday was taken in good faith and the issues raised by the DSMB may be a mere technicality, yet this won’t be clear until we have full disclosure," Griffin said. "Nevertheless, we must ensure that issues such as this are dealt with appropriately and that idle speculation is not seized upon by groups seeking to undermine faith in vaccination programs.”
More Data Planned for FDA
The placebo controlled clinical trial with 32,449 participants revealed 141 cases of symptomatic COVID-19. However, no data on how many of these cases were mild to moderate in the vaccine versus placebo groups was available. "We don't have the whole breakdown yet … these are the high-level results we just got this week," Menelas Pangalos, executive vice president of biopharmaceuticals research and development at AstraZeneca, said during a March 22 press briefing.
Pangolas indicated the company would have complete data available by the time they file a request for emergency use authorization of their vaccine, likely in the first half of April. He added the trial is ongoing and the FDA will receive information on more than the 141 cases at that time, he added.