Randomized controlled trials show all-cause mortality reduction from the Covid adenovirus-vector vaccines (RR=0.37, 95%CI: 0.19-0.70) but not from the mRNA vaccines (RR=1.03, 95%CI 0.63-1.71).
That is the verdict from a new
Danish study by Dr. Christine Benn and colleagues. Have people been given vaccines that don’t work (Pfizer/Moderna) instead of vaccines that do work (AstraZeneca/Johnson & Johnson)? Let’s put this study into context and then delve into the numbers.
In medicine, the gold standard for evidence is randomized controlled trials (RCT), as they avoid study bias for or against the vaccine. Moreover, the key outcome is death. Do these vaccines save lives? Hence, the Danish study answers the right question with the right data.
It is the first study to do so.
When the Pfizer and Moderna mRNA vaccines were approved by the US Food and Drug Administration (FDA), that decision was based on RCTs. The RCTs submitted to the FDA showed that the vaccines reduce symptomatic Covid infections. By recruiting mostly younger and middle-aged adults, who are unlikely to die from Covid no matter what,
the studies were not designed to determine whether the vaccines also reduce mortality.
That was assumed as a corollary, although it may or may not be true. Neither were the RCTs designed to determine whether the vaccines reduce transmission, but that is a different story for another time.
There is clear evidence that the adenovirus-vector vaccines reduced mortality.
For every 100 deaths in the unvaccinated, there are only 37 deaths among the vaccinated, with a 95% confidence interval of 19 to 70 deaths. This result comes from five different RCTs for three different vaccines, but it is primarily driven by the AstraZeneca and Johnson & Johnson vaccines.
For the mRNA vaccines, on the other hand, there was no evidence of a mortality reduction. For every 100 deaths among the unvaccinated, there are 103 deaths among the vaccinated, with a 95% confidence interval of 63 to 171 deaths.
That is, the mRNA vaccines may reduce mortality a little bit, or they may increase it; we do not know. The Pfizer and Moderna vaccines contributed equally to this result, so there is no evidence that one is better or worse than the other.
While all-cause mortality is what matters for public health, there is scientific interest in knowing how the different vaccines affect different types of mortality. The Danish scientists contacted RCT investigators to get information on whether each death was due to Covid, cardiovascular disease, accidents, or other causes.
For the mRNA vaccines, there was a reduction in Covid deaths but an increase in cardiovascular deaths, but neither was statistically significant. So, either result could be due to random chance. Alternatively, the vaccines may reduce the risk for Covid deaths while increasing the risk for cardiovascular deaths. We do not know, and Pfizer and Moderna did not design the RCTs to let us know.