On Nov. 8, the Food and Drug Administration published a report updating the clinical trial results of Pfizer's mRNA-based COVID-19 vaccine. The trial included around 44,000 people over the age of 16, equally divided into two groups. One group received the vaccine and the other a placebo.
Page 23 of the report showed that over the course of the trial, there were a total of 38 deaths among participants: 21 in the vaccinated group and 17 in the placebo group. Because the number of deaths in the vaccinated group was not significantly less than the placebo group (but is, in fact, more than the placebo group), the vaccine failed to prove itself by the standard of all-cause mortality.
All-cause mortality is the number of deaths due to any cause in both the control and treated groups of a clinical trial. This is the most reliable clinical endpoint for the evaluation of a medical treatment that is supposed to reduce mortality because it is objective and properly accounts for unanticipated effects, which may offset the anticipated benefits of a treatment.
The National Academy of Sciences published a volume that explained the evaluative advantage of all-cause mortality with many lessons from the annals of medical history. A contributor to the volume, renowned anesthetist John P. Bunker, said: "When dealing with mortality as an endpoint of treatment, all-cause mortality is ignored at the peril of the investigators and the public."
The burden of proving statistical significance is on the vaccine, not the placebo. The primary hypothesis of the clinical trial was that the vaccine would save lives, and for the hypothesis to be upheld, the death rate in the vaccinated group had to be significantly less than that of the placebo group – which did not happen in this case.
There is currently no scientific basis for retaining the hypothesis that the administration of the Pfizer COVID-19 vaccine could save lives.
However, there are reasons besides vaccination why the COVID death rate may be higher in one society than another, including population-age distributions, vaccinations and even access to therapeutics. The most obvious problem, however, is the reinforcing bias of the clinician, who knows whether or not the patient has been COVID-vaccinated. Among multiple comorbidities, the clinician might be more likely to attribute the death to COVID if he or she knows that the patient is not vaccinated.
If this happens, then the clinicians in populations with a higher vaccination rate would be less likely to attribute the deaths to COVID than the clinicians in populations with lower vaccination rates.
Because Pfizer's COVID-19 vaccine doesn't have a successful trial for all-cause mortality, it still remains experimental. (Related: Critics blasts FDA for full "approval" of Pfizer vaccine.)
None of the trials were designed to detect a reduction in any serious outcomes such as hospitalizations and deaths. While the vaccines are hailed to be the solution to the pandemic, clinical trials could not and did not prove that they can save lives. None of the vaccines studied were supported by concrete evidence to be able to interrupt the transmission of the virus.
Part of the reason for the lack of convincing results may be the numbers, because most people with symptomatic COVID-19 infections only experience mild symptoms, even for trials involving 30,000 or more patients.
"Hospitalizations and deaths from covid-19 are simply too uncommon in the population being studied for an effective vaccine to demonstrate statistically significant differences in a trial of 30,000 people. The same is true regarding whether it can save lives or prevent transmission. The trials are not designed to find out," said Peter Doshi, associate editor at the global healthcare knowledge publication, BMJ.
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