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Vaccine development

As you may know, there are coronavirus vaccines that are now released under Emergency Use Authorization.

The following is a description of how vaccines are developed and tested for efficacy and safety. The typical sequence of steps in vaccine development begins with testing vaccines in animals such as mice and non-human primates.

This testing is primarily to determine if the vaccine being evaluated generates an immune response. This is assessed by measuring antibody levels to the virus in question after the vaccine is administered. If there is no antibody response to the vaccine, things come to a screeching halt and it’s back to the drawing board.

The other important issue is to determine that the vaccine isn’t harming the animal. Severe or frequent adverse events also puts the investigators back to the drawing board.

If the vaccine looks promising and safe, Phase 1 trials are initiated. This involves using human subjects, usually a group of about 100 people, usually in the age range of 18-55 for adult vaccines.

Again, evidence of an immune response to the vaccine and the absence of significant side effects are assessed. If the vaccine again appears promising and safe, the next step is a Phase 2 trial.

These trials involve larger numbers of people, usually several hundred subjects and again involves evaluation of objective evidence of an immune response based on blood testing, and the presence or absence of side effects.

Phase 2 studies exemplify the statistical principle that a larger sample size of subjects increases the likelihood that the observed results are not due strictly to random chance.

If Phase 2 studies indicate that the vaccine has some promise of efficacy and is safe, Phase 3 studies are initiated.

Unlike Phase 1 and 2 studies, Phase 3 studies focus on how effective the vaccine is in preventing the disease in question. In order to do this and avoid bias in the interpretation of the results, Phase 3 studies employ a control group and the numbers of subjects are much larger.

For example, the studies on the Pfizer Covid-19 vaccine included about 36,000 subjects. The 2 groups studied were randomized, but also matched so that they are similar in age, race, gender, as well as overall general health factors.

An example of a vaccine study that would be flawed would be one in which the control group had significantly more people with an underlying condition like COPD, and the vaccine group had fewer people with this diagnosis.

This distribution would significantly skew the results in favor of the vaccine group. The other mechanism to reduce bias is “blinding.” That is, a vaccine study would be set up so that neither the subjects nor the investigators know who got the real vaccine and who got the placebo until the end of the study.

All the subjects are assessed equally. In the Covid vaccine trials, measurements included number of people who got sick with Covid-19, included measured levels of antibodies to SARS CoV2, and measured adverse events, such as fever, muscle aching and any other new symptom that the patient didn’t have at the beginning of the trial.

At the end of the trial, the “code is cracked” – that is, at that point, the investigators discover out who got the real vaccine and who got the placebo. Then, they can compare the 2 groups and see what effect the vaccine had.

The key measure is the percent reduction in the incidence of the disease. In the Pfizer trials, it was determined that the vaccine had an overall 95% efficacy. This was measured 7 days and beyond after receipt of the 2nd dose of vaccine.

In the study, there were 170 confirmed cases of Covid 19; 162 in the placebo group and 8 in the vaccine group. In patients over 65, there was a 91% efficacy.

Of interest, in the 2-week period between the 1st and 2nd injections, there was a 52% reduction in Covid cases in the vaccine group, compared to the placebo group.

In the trials of another Covid 19 vaccine, manufactured by Moderna, the overall efficacy was 94% and in patients over 65 was about 86%.

 There have been episodes of anaphylaxis, a severe allergic reaction, in a couple of vaccine recipients since the vaccine’s release. The pre-release vaccine studies showed that this side effect was quite rare.

Bell’s palsy was also noted, but the rate of this complication did not exceed the usual rate of occurrence of Bell’s palsy in unvaccinated patients, so a cause-and-effect relation is not clear.

Follow-up on vectors and masks

Two columns ago, I discussed the concept of vectors. It was not my intent that people who deliberately don’t wear masks should be compared to insects. My point was that an insect is usually a potentially “healthy carrier” of an organism that could be harmful to humans.

Insects don’t deliberately transmit diseases to humans. About 40% of humans with Covid-19 do not have and will not ever develop symptoms, but they can transmit the disease.

Unlike humans, however, insects are unable to behave in a way that reduces the risk of disease transmission. The scientific data overwhelmingly demonstrate that humans, by utilizing social distancing, hand washing and mask wearing, can reduce the risk of disease transmission.

As Maryland Gov. Larry Hogan so eloquently stated in recently televised public service announcements, “Wear the damn mask.”

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