The Great Vaccine Debate PART 3: What are efficacy and safety?

            A major point of disagreement between people when discussing the COVID-19 vaccines is over whether they “work”. “Safe and effective” are words that constitute a mantra for vaccine advocates and a trigger for many vaccine skeptics. I want to scream when I see ads with soft music and condescending narration, implying vaccinating your children is an act of kindness and that they will love you for it. I am tempted to unfriend people with “I got my COVID vaccine” profile frames. I understand why these words “safe and effective” now need a trigger warning. Forcing vaccines on people, coercing them by threatening their education and livelihood if they don’t get them, even insidiously convincing people that don’t need them to take them is wrong. Hard stop. However, insisting no one should take the vaccine (and that’s what you are saying if you object to an acknowledgment of any efficacy) is the flip side of the vaccine mandate coin. It’s an attitude that is equivalent to the attack we saw on early COVID treatments over the last two years. We need to look at the data critically and make an informed decision-and that may not be the same for each individual. That’s my stance and I am not hiding a secret agenda to spout the same pro-vaccine narrative as the public health officials. My goal is to transparently explain what is known. Even if you believe the adverse events of these shots are grossly underreported and the efficacy greatly exaggerated-to the point where the cost/benefit is too great for any individual to take them, we should all be on the same side when it comes to assessing what constitutes efficacy and safety. So, bear with me and let’s look at the science behind the terms safe and effective.

            First and most important: safety and efficacy are relative terms, and they will not be the same for each individual and they will differ depending on the method for determining them. The term efficacy is usually based on clinical trial data in which COVID infections (determined by test positivity and/or symptoms), hospitalizations, and deaths are examined in groups receiving either the vaccine or a placebo and the ratio of incidences in each group are used to calculate risk ratios. Safety is usually not reported as a risk ratio, but death and serious adverse events from the treatment are required to occur below a specific threshold to past safety standards. The safety bar should be much higher for a non-fatal disease and even higher in order to mandate a medical treatment. However, the misconception regarding how fatal COVID-19 is, along with the belief that anyone can transmit it, has impacted perceived cost/benefit assessment of the vaccines.

Let’s look at efficacy first. In the initial clinical studies on the Pfizer vaccine (https://www.nejm.org/doi/full/10.1056/nejmoa2034577), they reported 8 out of 18,198 participants (0.044%) in the vaccine group and 162 out of 18,325 (0.88%) in the placebo group contracted COVID-19 over the course of the study which followed them for up to 2 months after the second shot. What they didn’t emphasize was that infections were low in both groups, with 99.936% of those receiving the vaccine and 99.12% of those receiving the placebo NOT contracting COVID-19. For the Moderna vaccine (https://www.fda.gov/media/144434/download), similar data were obtained (6 COVID cases out of 15,180 (.042%) in the vaccine group and 92 out of 15,120 (0.6%) of the placebo group. There were clearly fewer infections in the vaccinated group than placebo for both vaccines, but when fewer than 1% of your control group actually contract the disease against which you are vaccinating, it is difficult to argue for mandatory vaccines.

Regardless of your feelings about vaccines, and despite the distasteful fear-mongering and over-reporting of death counts by the media, it is still important to know whether there is a possibility that vaccines could reduce the risk for those who really are dying from COVID-19. The method used to calculate efficacy in the clinical trials is based on the “infection risk ratio” or IRR, which is simply the ratio of case rates in vaccine group compared to the placebo group. If the IRR is substantially less than one, the vaccine is deemed reduce the risk of disease. If you simply calculated disease incidence based on the percentage of people in each group that contracted COVID in the initial trials, the IRR would be 0.044/0.88=0.05 for Pfizer, and 0.042/0.6=0.07 for Moderna). However, this doesn’t account for the fact that not everyone who tested positive did so at the same time and not everyone was monitored for the same length of time. Therefore, they used a method that takes the number of people in each group and how long after the second shot the data were collected to determine the “1000 person years of follow-up” values which is used as the denominator, instead of the number of people in each group, to calculate IRR. Efficacy was then determined by the following formula: 100*(1-IRR), where IRR is the ratio of confirmed cases per 1000 person years of follow-up in vaccinated compared to unvaccinated individuals. Using this method, they determined that the efficacy was 95% for Pfizer and 93% for Moderna. In this way, the fact that less than 1% of the people in either group contracted the disease is turned into a claim that the vaccine makes you 90-95% less likely to contract the disease. The Pfizer study was followed up at 6 months after the 2nd injection (https://www.nejm.org/doi/full/10.1056/nejmoa2110345) and they identified 82 cases out of 22,132 (0.37%) in the vaccine group and 889 out of 22,001 (4%) in the placebo. Using the “person-years” metric to calculate IRR, gives a value of .083 which translates into 91.7% efficacy. Looking at the breakdown in cases over time, the efficacy goes from 95% in the first two months to 84% at 6-months, i.e., efficacy is waning-thus the push for boosters. Once again, COVID-19 cases were not high in either group (at the 6-month point, 0.2% of the vaccine group and 1% of the placebo group developed COVID-19 and/or tested positive). More recently, efficacy of the Pfizer vaccine in adolescents ages 12-17 has been assessed (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174030/), and found 0 COVID-19 infections out of 1131 participants in the vaccine group compared to 41 out of 1129 (3.6%) in the placebo group up to 4 months after the 2nd dose.

The next question regarding efficacy is whether the vaccines prevented severe COVID and/or death, which is particularly important if they are calling a positive test in the absence of symptoms a case.  In the Pfizer study, the incidence of severe COVID-19 or death was also extremely low in both groups: 13 people in the placebo group (0.08%) developed severe COVID-19 symptoms, compared to 2 people in the vaccine group (.009%)-an IRR of 0.113. Of course, since fewer people in the vaccine group contracted COVID, that corresponds to 25% of vaccinated COVID cases compared to 8% placebo COVID cases being severe. Does that mean the vaccine worsens the disease if you get it? No, I would not make that argument; in the Moderna study, 0 individuals in the vaccine group developed severe COVID-19, compared to 30 (.2%) of the placebo group. The bottom line is that the data do not suggest an additional protection against severe disease in those who were vaccinated. Those claims of “protects against severe disease and death” primarily came from epidemiological studies on hospitalizations and deaths among those who were and were not vaccinated, without taking into account other factors.

Now, let’s move to safety, which is defined by the incidence of adverse events. The adverse events that have come to light over the past year (e.g., myocarditis) are more severe than those typically reported in the clinical trials. The average age in these trials was approximately 50, while myocarditis more frequently occurs in younger individuals, which may explain why it wasn’t observed. In these first clinical studies, the primary side effects were “comfort” related, i.e., injection site pain, fever, fatigue, headache, and muscle pain. A handful of what they deemed “severe adverse events” in less than 1% of the participants. Looking at the Pfizer trial data, (https://www.nejm.org/doi/suppl/10.1056/NEJMoa2110345/suppl_file/nejmoa2110345_appendix.pdf), the overall incidence of death was 15 (0.07%) in the vaccine group and 14 (0.064%) in the placebo group. Some of the deaths were from causes that had to be unrelated to the clinical trial: one death in the placebo group was an overdose, one was metastatic cancer, and one was dementia; three deaths in the vaccine group were metastatic cancer and one was a Shigella infection.  If you remove those deaths from the data, you see no difference in death risk between the two groups. The data reveal that 2 of the deaths in the placebo group were due to COVID-19 and 1 in the vaccine group was due to “COVID-19 pneumonia” which has led some to claim that the risk of death from COVID was 50% lower in the vaccine group. Likewise, there were 4 incidences of cardiac arrest in the vaccine group (0.02%) and 1 incidence of cardiac arrest in the placebo group (0.005%), leading one person who commented on my previous article to claim that Pfizer allowed 3 cardiac deaths to prevent 1 COVID death, and led others on social media to claim the vaccine increases the risk of heart attack by 75%. Both the assessment of vaccine-induced protection from COVID death and vaccine-induced heart attacks are misleading. Once again, both death from COVID and cardiac arrest occurred in a small percentage of the participants. There were no data presented on the conditions of those who suffered cardiac arrest, and whether they were already in a high-risk group for heart attack prior to the study. The powers that be will argue that the risk of death from COVID-19 is higher than the risk from the vaccine, which may be true for those in high-risk categories, but very well may not be for healthy individuals. The possibility of vaccine-induced cardiac events should not be dismissed, as there is no more evidence for protection from COVID death than there is increased risk for heart attack in these data.  This is yet another reason that mandating the vaccines, and coercing people to get them is immoral. However, to win this battle, we need to avoid playing the same game the medical authoritarians are playing. The science speaks for itself. These are too risky to mandate. They are not too risky to offer the vaccine to those who want it, but honesty and transparency are critical.

Reports of myocarditis did not emerge into the mainstream consciousness until after the vaccine roll-out had begun and appear to affect younger people (particularly men) more than those who are actually at risk of complications from COVID-19. The reports to date are summarized in this article (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971371/) and the fact that the VAERS-reported incidence of myocarditis amounts to only 0.002% of the vaccinations administered to individuals in the 18-29 age group that has led the public health officials to dismiss these reports as nominal. However, the risk of death from COVID-19 is also very low-less than .05% in that age group, and 99% of those deaths were in individuals with serious comorbidities, meaning the risk of COVID is negligible in most 18–29-year-olds. Because most of the myocarditis reports are through VAERS, there isn’t readily available information on the health of these individuals prior to receiving vaccines; we are left with case reports of healthy kids developing serious myocarditis, which is exploited by the public health establishment to write it off as extremely rare. As more data emerge, it is very likely that the risk from myocarditis, although low, is higher than that of COVID-19 for young and healthy individuals. The study on the Pfizer vaccine in adolescents did identify adverse events in the vaccine group, but the authors claim they were unrelated to the treatment (although they don’t explain how they came to that determination). There were no deaths in either group, but there were 7 severe events (2 classified as “adverse”) in the vaccine group (0.6%) compared to 2 severe events (1 classified as “adverse”) in the placebo group (0.18%). If you use the deceptive risk ratio calculation would suggest there was a 3.5-times greater risk of severe events and a 2-fold increase in severe adverse events with the vaccine. It appears that severe adverse events were determined using a blood chemistry panel to look for signs of toxicity, but the nature of those that were observed in the study was not revealed. Given the very low risk or serious complications from COVID in this age group (less than 0.01%), I would argue these low-frequency risks are high enough that they should be weighed for each individual.

Even if we were to move away from the low incidence events and look at commonly reported fever and joint pain, the risk ratio for these events was significantly increased by the vaccine, to the same extent that infection risk ratio was decreased.  For example, grade 3 joint pain occurred in 5.7% of Moderna vaccine recipients and only 0.3% of placebo recipients, which is a risk ratio of 0.05 for placebo vs vaccine, the same as the infection risk ratio for vaccine vs placebo. The argument that would be put forth is that the joint pain isn’t going to “kill you” which relies on the exaggeration of death risk from COVID-19 of which the public health establishment is so fond. It is unconscionable practice when the goal is to force a drug on everyone and ridicule individual’s concerns.