https://www.fda.gov/media/144859/download

I've been going through this transcript from the Dec 2020 FOOD AND DRUG ADMINISTRATION (FDA) Center for Biologics Evaluation and Research (CBER) 162nd Vaccines and Related Biological Products Advisory Committee (VRBPAC) Meeting. It's a pretty interesting discussion although I don't understand much of it. From what I've read, all of the doctors recognize the need for a vaccine with some questioning the necessity for healthy people getting it. Also, it shows how few decisions makers, even with red tape and agencies, actually make the decisions for the country. Even pzifer's manufacturing of the vaccine is proprietary so any discussion was off limits. That must be a difficult realization for doctors. Any way, Here's a snippet from the Pfizer doctor:

Pg 223
"We performed an interim analysis at 94 cases
4 in individuals without prior infection and observed
5 efficacy of 95.7 percent. We have now also performed
6 the final vaccine efficacy evaluation against COVID-19
7 occurrence from seven days after dose two in 170 cases
8 without evidence of prior infection. Observed efficacy
9 is high at 95 percent, with high confidence based on
10 the parameters shown in the two right-hand columns.
11 There's 95 percent probability that efficacy
12 falls in the intervals shown; meaning, that over 97.5
13 percent likelihood that efficacy is greater than 90
14 percent. Likewise, the probability that vaccine
15 efficacy is at least greater than 30 percent greatly
16 exceeds FDA COVID-19 vaccine guidance."

Can someone explain the validity of efficacy without infecting the vaccinated? I get that ethics probably wouldn't allow that, but it seams that measuring efficacy on an uninfected person is misleading.

This was also interesting. From a Pfizer Doctor:

DR. WILLIAM GRUBER: Thank you, Kathrin. It's
9 my pleasure to share with you today the development
10 program for our vaccine candidate BNT162b2. I'm going
11 to begin with a very brief summary of the non-clinical
12 data that encouraged us to move forward into the
13 clinic. This includes both toxicity studies as well as
14 a study looking at a challenge study in Rhesus-
15 Macaques. These studies are described in the briefing
16 documents.
17 Two toxicity studies in rats, including the
18 BNT162b2 vaccine construct, were completed with no
19 safety concerns. Development and reproductive toxicity
20 studies are ongoing with preliminary results available
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1 by mid-December. In a SARS-CoV-2 Rhesus challenge
2 model, the BNT162b2 construct provided complete
3 protection in the lungs as determined by nucleic acid
4 amplification testing for SARS-CoV-2 and
5 bronchoalveolar lavage fluid. This information is now
6 published. And importantly, there was no radiologic or
7 histopathologic evidence of vaccine-elicited disease
8 enhancement.
9 Despite limitations of animal models, these
10 findings anticipated results in our Phase 3 clinical
11 trial in which there is no evidence of enhanced
12 disease. These results were encouraging, satisfied FDA
13 guidance criteria, and permitted progression of human
14 clinical trials. I'm now going to share with you the
15 clinical safety, immunogenicity, and efficacy data from
16 our overall clinical development program.
17 First, I will cover safety and immune response
18 from the German and U.S. studies and then cover aspects
19 of the Phase 2/3 trial finishings with the safety and
20 efficacy results. So let's begin with the two Phase 1
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1 studies. The German Phase 1 dose-ranging study was
2 conducted in individuals 18 to 55 years of age. 12
3 subjects received the active BNT162b2 vaccine for each
4 dose level cohort. This study evaluated safety,
5 binding, and neutralizing antibody responses, as well
6 as cell-mediated immune response to look for the
7 potential for Th 1-biased, CD4, and CD8 T Cell
8 responses.
9 The U.S. study is a seamless study where we
10 have a Phase 1 portion that moved into Phase 2 and then
11 Phase 3. For the Phase 1 dose-ranging portion, we
12 included 18 to 55 and 65 to 85-year-old individuals.
13 Twelve of whom received vaccine and 3 received placebo
14 per dose-level cohort. We looked at safety and
15 immunogenicity with both binding and neutralizing
16 antibody responses and followed reactogenicity by
17 electronic diary.
18 These individuals will continue to be followed
19 for a full two years after the second dose. The
20 results from the Phase 1 experience have now been www.transcriptionetc.com
207

1 published and you have details in your briefing
2 documents."

I'm curious the length of time the studies went from rats to humans. And also why only use 12 humans for a trial? Sorry if I'm misinterpreting this.

texan12 said:

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https://www.fda.gov/media/144859/download

I've been going through this transcript from the Dec 2020 FOOD AND DRUG ADMINISTRATION (FDA) Center for Biologics Evaluation and Research (CBER) 162nd Vaccines and Related Biological Products Advisory Committee (VRBPAC) Meeting. It's a pretty interesting discussion although I don't understand much of it. From what I've read, all of the doctors recognize the need for a vaccine with some questioning the necessity for healthy people getting it. Also, it shows how few decisions makers, even with red tape and agencies, actually make the decisions for the country. Even pzifer's manufacturing of the vaccine is proprietary so any discussion was off limits. That must be a difficult realization for doctors. Any way, Here's a snippet from the Pfizer doctor:

Pg 223
"We performed an interim analysis at 94 cases
4 in individuals without prior infection and observed
5 efficacy of 95.7 percent. We have now also performed
6 the final vaccine efficacy evaluation against COVID-19
7 occurrence from seven days after dose two in 170 cases
8 without evidence of prior infection. Observed efficacy
9 is high at 95 percent, with high confidence based on
10 the parameters shown in the two right-hand columns.
11 There's 95 percent probability that efficacy
12 falls in the intervals shown; meaning, that over 97.5
13 percent likelihood that efficacy is greater than 90
14 percent. Likewise, the probability that vaccine
15 efficacy is at least greater than 30 percent greatly
16 exceeds FDA COVID-19 vaccine guidance."

Can someone explain the validity of efficacy without infecting the vaccinated? I get that ethics probably wouldn't allow that, but it seams that measuring efficacy on an uninfected person is misleading.

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I haven't read the study, and I am not a statistician, I slept at home last night and NOT in a Holiday Inn Express. When I was little, I did do surveillance studies for a Haemophilus vaccine in Dallas County. You are absolutely correct that, with a novel virus without any approved therapeutics (when the studies were done), there is no way in hell that an institutional review board would approve of a study infecting participants with a virus. Particularly since the best design would be against a placebo.

You can determine the efficacy of the vaccine by measuring against a cohort group (people out in the general public who have the same sex, age, geographic distribution, and likelihood of being exposed to a virus) and determining how many vaccinated persons should have gotten ill. However, patients who got a placebo serve as the best cohort you could have when you "double blind" the study, since they are hopefully as similar as possible to the vaccinated patients. You don't have to have the same number of controls as vaccinated patients, as long as you can "power" the study to be able to determine how many vaccinated study patients should have gotten the illness, versus how many patients did get the illness. So, if 10% of the unvaccinated (control) participants got ill, and all participants are treated the same, then out of 1,000 vaccinated participants, 100 of them should have gotten ill. If only 5 did, you're demonstrating 95% efficacy at preventing illness. I could be totally mininterpreting your question, but...

Appreciate the clarification