Fauci: DSMB Challenge of New AstraZeneca COVID-19 Vaccine Data Is an ‘Unfortunate Incident’
Following a review of the latest interim data released by AstraZeneca on its US phase 3 clinical trial assessing the 2-dose AZD1222 COVID-19 vaccine, the Data and Safety Monitoring Board (DSMB) expressed concern at the inclusion of what may have been outdated data.
Following a review of the latest interim data released by AstraZeneca on its US phase 3 clinical trial assessing the 2-dose AZD1222 COVID-19 vaccine, the Data and Safety Monitoring Board (DSMB) expressed concern at the inclusion of what may have been outdated data. Due to this concern, the National Institute of Allergic and Infectious Disease (NIAID) released a statement urging AstraZeneca to work with the DSMB to review its efficacy data and ensure “the most accurate, up-to-date efficacy data be made public as quickly as possible.”
In the report that DSMB sent on Tuesday morning to NIAID, AstraZeneca, and the US Biomedical Advanced Research and Development Authority (BARDA), the monitoring board explained that the inclusion of outdated information “may have provided an incomplete view of the efficacy data.”
AstraZeneca responded to this claim regarding outdated data by explaining in a press release that the efficacy rate of its COVID-19 vaccine AZD1222 that the company had reported Monday morning came from pre-specified interim analysis that had a data cut-off date of February 17, 2021.
"We have reviewed the preliminary assessment of the primary analysis and the results were consistent with the interim analysis," the company wrote in the press release. "We are now completing the validation of the statistical analysis."
In the press release, AstraZeneca went on to explain that they will work with DSMB and share the trial’s primary analysis with the most up to date efficacy data available. AstraZeneca noted that it will then release the results of that primary analysis to the public within 48 hours.
Following AstraZeneca’s response to the DSMB report, NIAID Director Anthony Fauci, MD, explained on Tuesday morning during an interview on "Good Morning America" that the whole incident was unfortunate, as DSMB’s concern was due to an "unforced error" by AstraZeneca.
"When they saw that press release, they got concerned, and wrote a rather harsh note to them, copied to me, saying that in fact, they felt the data that was in the press release were somewhat outdated and might in fact be misleading a bit, and wanted them to straighten it out," Fauci said during the interview, according to an article on ContagionLive.
Fauci noted that this incident was additionally disadvantageous due to it potentially contributing to concerns among some in the general public that have given rise to an increase in vaccine hesitancy.
"The fact is, this is very likely a good vaccine, and this kind of thing does nothing except cast some doubt about the vaccines and maybe contribute to the hesitancy," he said during the interview. "It was not necessary. When you look at the data, they really are quite good. When they put it into the press release, it wasn't completely accurate."
Specifically, there have been other concerns that have arisen regarding AstraZeneca’s AZD1222 vaccine globally, which most recently led to Denmark, Norway, and Iceland suspending the vaccine’s use due to reports of severe blood clots among some vaccinated persons. However, independent reviewers investigated these cases and have since cleared the vaccine of causal association to neurological or thrombotic events.
In the United States, AstraZeneca has pursued US regulatory consideration for AZD1222 for almost a year, the length of which was caused by setbacks that arose during the US phase 3 trial assessing the vaccine. The trial was paused for 7 weeks in September 2020 after a pair of non-fatal, hospitalizing neurological adverse events occurred in placebo participants.
In May 2020, AZD1222 was among the first COVID-19 vaccine candidates to demonstrate positive phase 1 immunogenicity data, generating enthusiasm for the arrival of further results. This led to BARDA making a $1.2 billion agreement with AstraZeneca over the summer for millions of AZD1222 vaccine doses to be shipped to the United States. AstraZeneca proceeded to collaborate with the University of Oxford, continuing its publicization globally and amplifying its resources.
However, following further positive AZD1222 trials results released in Europe, in February 2021, South Africa health authorities announced their plans to withhold further AZD1222 vaccine administration to the country’s frontline health care professionals. In the region, there was greater transmission of the B.1351 variant of SARS-CoV-2, leading to trial results on AZD1222 demonstrating an approximate 20% efficacy in preventing COVID-19 in patients from region.
However, AZD1222 has been authorized for use in more than 70 countries, with real-world data supporting its continued efficacy among these populations. Yet due to it remaining unauthorized in the United States, millions of AZD1222 doses are stockpiled in the country, with plans for distribution to commence upon the receipt of positive US phase 3 clinical data.
Despite these delays in the authorization of AstraZeneca’s AZD1222 vaccine, COVID-19 vaccines from Pfizer-BioNTech, Moderna, and Johnson & Johnson have received Emergency Use Authorization in the United States. To date, more than 25% of the US population has received at least 1 COVID-19 vaccine dose, with approximately 14% fully vaccinated.
Kunzmann K. NIAID Challenges New AstraZeneca COVID-19 Vaccine Data. ContagionLive. March 23, 2021. https://www.contagionlive.com/view/pfizer-biontech-vaccine-protects-skilled-nursing-facility-residents-as-effectively-as-general-population. Accessed March 23, 2021.