Yesterday a new paper surfaced in a non-peer reviewed form on a Lancet website. It was from AstraZeneca and Oxford University scientists and claimed additional new information from the phase three U.K. trial of their COVID-19 vaccine. The paper also suggested that this vaccine appeared to be effective in preventing transmission of COVID-19.
Once again, however, as with AstraZeneca’s prior announcements on this vaccine, the data appeared to be less convincing than either headline would suggest. More importantly, the incomplete and confusing data AstraZeneca presents seem to be driving public health decisions in the U.K. that have profound impact.
The AstraZeneca and Oxford scientists report that (two doses of) their vaccine were overall 66.7% effective in protecting against COVID-19 disease. This is again the low end of the efficacy spectrum for COVID-19 vaccines and equal to the one dose vaccine from Johnson and Johnson reported last week. In contrast, Moderna’s and PfizerBioNTech’s vaccines are both 94% to 95% effective in protecting against COVID-19 disease after two shots.
The AstraZeneca trial was further clouded by the fact the trial underwent changes after it was begun, an absolute no-no in clinical research. The study was initially designed to give a single dose of the vaccine. After a single shot, 76% of participants were protected against disease for three months afterwards. After that, the levels of protective antibodies generated against the virus began to drop. The authors suggested that despite this, a single dose could still be useful for about three months in controlling COVID-19, especially if there were vaccine shortfalls.
Two doses of the vaccine, however, were much better at providing protection from COVID-19. The data also suggested that spacing the vaccine doses over three months could increase their level of protection. Those who got the second dose longer than 12 weeks after the first were 82.4% protected against COVID-19 disease as compared to those who got a second dose in less than six weeks (54.9% effective). These changes too were made after the trial started.
This is also the clinical trial during which mistakes were made in measuring doses, giving some people a half dose initial shot and a full dose second one. This trial also varied the placebo, with some individuals receiving meningococcal vaccine and some a saline solution. That could alter the innate immunity in some placebo recipients and confound the results. Finally, because of supply limitations, study participants had to wait varied times for their second dose and others never received their second shot.
Experts were not impressed by these results, suggesting a poor reception for this vaccine on peer review. The Swiss regulatory body refused to approve this vaccine based on this trial. As stated on February 3, due to the changes after the Phase 3 trial was begun, it was impossible to make a final determination of vaccine efficacy. Other experts were more pointed. “Frankly the way they did these trials was really confusing,” says Dr. Paul Offit, director of the vaccine center at Children’s Hospital of Philadelphia and a member of the U.S. Food and Drug Administration’s advisory committee that reviews vaccines. The AstraZeneca vaccine approval in the U.S. awaits the results of their late-stage studies here.
The other headline stated that this vaccine “prevented transmission of COVID-19.” This was asserted because the investigators found that positive COVID-19 PCR tests were about 50% lower among people who got two doses of the vaccine compared to those who weren’t vaccinated. Because of this, the researchers suggested that the AstraZeneca vaccine could lower transmission of the COVID-19 virus.
This statement was also derided by multiple experts including Dr. Carlos del Rio of Emory School of Medicine. “It’s a leap of science that I think still needs to be proven,” he says. “What they show is that there was [either] decreased viral shedding or decreased detection of virus.” However, they do not actually show that transmission was decreased. “We can say less transmission is a possibility, but the data on that needs to come out,” says Del Rio. “We want to state the facts and don’t want to overstate the facts.”
I personally believe most vaccines would decrease viral shedding and the better vaccines would be more effective than AstraZeneca.
Most disconcerting, it is now clear that the U.K. used these flawed data to decide to hold all second doses of all COVID-19 vaccines as the results were lauded by British health secretary Matt Hancock. Holding the second doses of all the other COVID-19 vaccines based on the data from this trial with an entirely different vaccine is crazy.
Now that it is clear that two doses of the AZ vaccine are better, the U.K. is embarking on a new effort to mix and match other COVID-19 vaccine second doses with a previously administered AstraZeneca first dose, presumably to improve the AZ vaccine. This is not an appropriate way to test or use these vaccines.
At this point, it unfortunately looks like the U.K. is putting lives at risk just to support their own, flawed vaccine.