An AstraZeneca press release about the positive interim results from a new phase III trial (NCT04516746) met with controversy when the U.S. Data and Safety Monitoring Board (DSMB) issued a press release of its own that challenged the findings.
The AstraZeneca release stated in its headline that the phase III trial met its primary endpoint in preventing COVID-19 (www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/astrazeneca-us-vaccine-trial-met-primary-endpoint.html). It then stated that there was a significant vaccine efficacy rate of 79% in preventing symptomatic COVID-19 and a 100% efficacy at preventing severe disease and hospitalization. The interim analysis was based on 32,449 subjects in the U.S., South America and France. The phase III trial was conducted to gain FDA approval for the vaccine in the U.S. The interim results have not yet been peer-reviewed or published.
In its press release, the DSMB stated that it had notified AstraZeneca that it was concerned that the company’s press release “may have included outdated information from that trial, which may have provided an incomplete view of the efficacy data” (www.nih.gov/news-events/news-releases/niaid-statement-astrazeneca-vaccine). Dr. Anthony Fauci, Director of the DSMB, said that the AstraZeneca press release might be “misleading a bit”. “The data are quite good, but when they put it into the press release it wasn’t completely accurate,” Dr. Fauci told ABC News (https://abcnews.go.com/GMA/News/video/fauci-discusses-concerns-oxfordastrazeneca-vaccine-data-76626319).
One source of confusion may be that the headline claims efficacy in preventing COVID-19, whereas the efficacy results are in preventing symptomatic COVID-19. According to the study description on clinicaltrials.gov, the primary endpoint was the prevention of COVID-19; a COVID-19 case was defined as PCR-positive symptomatic illness occurring >15 days after the second vaccine dose. By these criteria, PCR-positive cases that are asymptomatic or occur prior to the 15-day cut-off, and symptomatic or suspected COVID-19 cases without PCR confirmation, would not be classified as a COVID case.
AstraZeneca issued a follow-up press release stating that it plans to release the results from its primary analysis later this week (www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/update-following-statement-by-niaid-on-azd1222-us-phase-iii-trial-data.html).
A further issue that has plagued the AstraZeneca vaccine is the link to rare thrombotic complications. To date, the European Medicines Agency has recorded 18 cases of cerebral venous sinus thrombosis (CVST) in approximately 20 million people receiving the AstraZeneca vaccine (www.ema.europa.eu/en/news/covid-19-vaccine-astrazeneca-benefits-still-outweigh-risks-despite-possible-link-rare-blood-clots). It has not been determined if vaccination is related to CVST or if this rate is higher than what is normally seen. As expected, no cases of thrombosis occurred in the recent AstraZeneca trial. It should be noted that the Canadian Product Monograph for the Janssen COVID-19 vaccine, another viral vector vaccine, did acknowledge a higher number of thromboembolic events (15 with vaccine vs. 10 with placebo) where the vaccine could not be excluded as a contributing factor.