“An Unforced Error”: US Expert Group Issues “Unprecedented” Statement on AstraZeneca Vaccine Trials

A further AstraZeneca press release has updated its earlier interim analysis with full primary analysis data for the company's COVID-19 vaccine. This new data suggests the vaccine is 76% effective at preventing symptomatic COVID-19 and is 85% effective in preventing symptoms in people over the age of 65. No safety concerns were raised [Updated March 25].

New data and a conflicting statement have added fresh twists to the already tumultuous progress of the Oxford-AstraZeneca COVID-19 vaccine.

The rumbling saga around the efficacy – the measure of how a vaccine performs in trial conditions  -of the COVID-19 vaccine developed by Oxford University in partnership with UK-Swedish manufacturer AstraZeneca was largely ground to a halt by the real-world data released by different branches of the UK’s health service last month.

That data showed the vaccine had an incredibly high effectiveness – the ability of a vaccine to prevent disease outside trial settings – despite the botched data that produced confusing efficacy results from trials in the UK. Roughly a month after receiving the vaccine, hospitalizations were reduced by 94%.

Despite this promising data, the vaccine still needed to undergo testing in the US to receive emergency use authorization by the Food and Drug Administration (FDA). The efficacy saga has now ground back into motion with the publication of initial data from the vaccine’s US trial, which was regarded by some experts as being of superior quality to the earlier UK trials. The headline figure, announced 22 March in an AstraZeneca press release, was of a 79% efficacy at preventing symptomatic COVID-19 infection – a figure higher than the result produced by earlier UK and Brazil-based trials.

The new trial, which involved over 30,000 patients from a variety of age groups and ethnic backgrounds, also reported that efficacy was maintained in older age groups – an important finding given the small number of older participants in earlier trials of the vaccine.

From a sigh to a groan

This produced an audible sigh of relief among experts concerned that the series of apparent errors committed by AstraZeneca during the trial process, alongside halts to the vaccine rollout due to safety investigations into vanishingly rare blood clots, would increase vaccine hesitancy, especially in European populations with ingrained anti-vaccine attitudes.

A subsequent statement released by the National Institute of Allergy and Infectious Diseases (NIAID) might see those relieved exhalations turn to frustrated groans. The statement detailed a notice of concern released by the Data and Safety Monitoring Board (DSMB), an independent expert group that advises the US National Institutes of Health (NIH). The DSMB, the notice said, were worried that AstraZeneca may have “included outdated information” in their results release, which could potentially result in “an incomplete view of the efficacy data.”

Commenting on the data, NIAID director Anthony Fauci told Good Morning America, “this is really what you call an unforced error, because the fact is, this is, very likely a very good vaccine.”

“Bad communication by NIH”

The rather threadbare nature of NIAID’s release drew ire from experts. “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,” commented Dr Peter English, a consultant in communicable disease control and the immediate past chair of the BMA Public Health Medicine Committee.

Speaking to Technology Networks, English commented further: “I have to say, it feels like mudslinging here. By issuing the statement without saying what the issue was, it invites speculation. It’s how malicious gossip starts. We simply don’t know what the issue was.”

English highlighted the need for additional vaccine data to be shared by the manufacturer, to allow proper scrutiny. “I was a bit disappointed that Astra Zeneca released its data as a press release without a preprint to provide more detail, although I think all the companies have been guilty of the same thing.”

Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, said a public statement of this kind was extremely unusual: “It is not unknown for a DSMB to disagree with investigators over interpretation of trial results. It is usually done in private, so this is unprecedented in my opinion.”

What could be behind the DSMB’s concerns? AstraZeneca’s release made clear that the DSMB had raised no safety concerns. Instead, said Evans, the explanation might be that the vaccine has been found to show reduced efficacy against a new variant of the virus. “It does not leave me concerned particularly unless they had found a safety issue that was being hidden, which does not appear to be the case,” said Evans.

Regardless of the statement from the DSMB, English says the real-world data has already validated that the vaccine is both safe and effective: “A few months ago we would have been delighted with a vaccine that was 50% effective. Now we are seeing data suggesting that the vaccine is 90+% effective at preventing severe disease.”

AstraZeneca responded to the NIAID release with its own brief, stating that “the numbers published yesterday were based on a pre-specified interim analysis with a data cut-off of 17 February.” The company would “immediately engage with the independent data safety monitoring board (DSMB) to share our primary analysis with the most up to date efficacy data.”

This article was updated March 25, 2021 to include new efficacy data from AstraZeneca.