Leading US vaccine expert Anthony Fauci, head of the National Institute of Allergy and Infectious Disease (NIAD), now chief medical advisor to US President Joe Biden, said the board had alerted him and other health officials to a discrepancy in figures and was worried that “outdated” data might provide an incomplete view of the vaccine’s efficacy. This could lower public acceptance. Fauci said on US television that he had “never seen anything like this.”

AstraZeneca said its published figures constituted a “preliminary assessment of the primary analysis” and that the results were consistent with its interim analysis. “We are now completing the validation of the statistical analysis,” the company said on its website, adding that it would “immediately engage” with the DSMB to share its primary analysis with the most up to date efficacy data.

US officials told the newspaper Washington Post that the board, made up of experts appointed to oversee ongoing clinical trials, had worked with AstraZeneca on its US trial and that under its structure an interim analysis of results was due to take place after 75 cases of Covid-19 had been detected among participants. This was to be followed by a so-called primary analysis after 150 cases.

In a widely quoted tweet, David Benkeser, an assistant professor of biostatistics at Emory University in Atlanta, Georgia US, criticized the drugmaker’s information policy. It appears, he said, that the threshold of cases for the primary analysis was reached while the interim analysis was still under way, and that AstraZeneca’s presentation is now causing confusion over which results it is reporting.

Stephen Evans, a pharmacoepidemiology professor at the London School of Hygiene and Tropical Medicine, called DSMB’s admonition to the company “unprecedented.” While noting that the board sometimes interprets trial results differently from other professionals, “this is usually done in private,” he told the UK’s Financial Times.

In its Mar. 22 report on the US trial, Astra Zeneca said its vaccine had proved 79% effective against symptomatic forms of Covid-19 and offered 100% protection against severe disease, hospitalization and death. In participants over 65, efficacy was even higher at 80%.

The company said the analysis was based on 32,449 volunteers from the US, Peru and Chile accruing 141 symptomatic cases of Covid-19 and had a 2:1 randomization of vaccine to placebo. It did not quantify how many cases occurred in the vaccine and the placebo groups respectively, which the experts said was perplexing.

Calling the open criticism “a rare window” into the typically confidential interactions between a company and the board that polices the integrity of trial data, US sources told the newspaper Washington Post the board had seen earlier figures from AstraZeneca suggesting the vaccine was 69% to 74% effective in preventing the disease. This was better than the 60% it estimated after the confusing trial that prompted the FDA to set new standards for the US tests but it was not as high as the 79% now reported.

AstraZeneca said in its presentation that it planned to apply to the FDA for an Emergency Use Authorization (EUA) in the first half of April, based on preliminary results.

Author: Dede Williams, Freelance Journalist