Extremely encouraging news from Pfizer this morning relating to their mRNA vaccine, Phase 3 testing results.
I thought that it would be valuable to look at what Pfizer has said and try to project and understand the results that were announced. Please understand that this was a Press Release, not a submitted scientific study, so a lot of the information is difficult to interpret. Even with those difficulties, this is very positive news.
Here is my interpretation of the Press Release (btw, I also read the 146 page Pfizer/BioNTech protocol).
Of the 43,538 enrolled people in this Phase 3 test about 90% have received a second dose. That second dose was given 21 days after the first dose, and the results reported are for patients with a minimum of 7 days having passed after the second dose was received.
The study included patients from the age of 12-55, so any approvals for use, emergency authorization or general distribution, will not be given for children under the age of 12 or seniors over the age of 55. These authorizations will be given AFTER additional studies are commenced and completed.
VACCINE WAS MORE THAN 90% EFFECTIVE
These numbers were derived from the numbers of people determined to be positive for COVID-19 in the period after 7 days subsequent to the receipt of the second dose of vaccine, or a total of 28 days after the initial dose was given.
Infection was determined by an NAAT test (this is a Nucleic Acid Amplification Test; the most common type of these tests is the one we have discussed at length, the PCR, or Polymerase Chain Reaction test. It tests for the presence of viral RNA in the individual, not for the presence of disease symptoms).
The TOTAL number of cases reported was 94. Among those 94 cases they report that 90% of the cases were found in the placebo group, 10% in the vaccine group. So, we can extrapolate to the numbers of about 85 cases in the placebo group and 9 in the vaccine group.
Here is the first point of potential misunderstanding with the data. If you look simply at the fact that there were only 9 cases in the vaccine group out of a group of 94, you get 85/94, or about 90.4% protection, hence the claim of “greater than 90% efficacy”.
But there is a problem in using this method of calculation. The real number should not be calculated in this way. Instead, you need to determine how many infections actually occurred in the vaccine group compared to the placebo group. Of the 94 cases detected, with NO treatment, and based on the numbers for that group (the placebo group), one would expect that 85 cases would be detected. However, when that same group of 85 expected patients were given vaccine, 9 became infected. So, the actual protection rate is 76/85, or 89.5%. Now, this may seem like a difference without a consequence, but the final data is not in yet and the total sample space here is only 94 positive cases out of 38,955 patients, or 0.2% of the patients in the study. If, for example the number rises from 9/94 to 30/164 (164 is the scheduled endpoint for the Phase 3 study), then the comparable numbers would be different.
In this case, using the gross number, cases within the vaccine group compared to the total group would be 81.7% protective efficacy. But if, instead we look at the protection from the expected group of infections 30/134, the efficacy rate would actually be 77.6%. The more cases uncovered in the vaccinated group, the lower the effectivity, but at a faster rate than just the gross numbers. And as we have discussed in the past, the efficacy rate is directly related to the percentage of the population needing to be vaccinated in order to achieve herd immunity. Every % is quite important.
WHAT DOES EFFECTIVITY MEAN?
At this time, we do not know the answer to this question.
We don’t know if the cases detected in the vaccinated group had no clinical symptoms, a few symptoms, hospitalizations, severe disease or deaths. The only thing we have is that those 9 effected individuals tested positive for viral RNA.
We don’t know if there were any other correlations with these people. Were they the youngest? The oldest? Skewed towards any particular demographic group? Geographic location group? Underlying medical conditions? In other words, until the raw data is distributed, we can’t really evaluate the results.
Finally, we don’t know how long immunity will last or whether it will be effective against viral variants circulating already in the population.
VACCINE TIMING
According to the Pfizer press release, they expect to be ready to apply for Emergency Use Authorization by the third week in November. This is the point at which they believe that they will reach the 164 identified case barrier. They are prohibited from applying for the EUA until they reach that 164-case total. After that EUA is submitted, it will take between 2 and 3 weeks for the FDA to review and act on the application. This is already an accelerated schedule. So, we are looking at mid-December before any EUA is issued.
Once an EUA is approved, Pfizer estimates that they can have around 50 million doses available world-wide by the end of 2020. With 2 doses required, that means they will have sufficient vaccine to inoculate a total of 25 million people WORLD-WIDE. In this country, Operation Warp Speed has geared up production of vaccine, so we can expect that there will be a large fraction of that vaccine available in this country late December. However, Operation Warp Speed is focused on production and distribution. The US government does not have a financial interest in Pfizer, nor has it provided financial support for Pfizer. The US government HAS pre-ordered and bought vaccine doses. Therefore, we can expect that there will be vaccine available in this country for particular at-risk groups. BUT, BUT, BUT, any authorization of the vaccine will ONLY be issued within the parameters of the study. Individuals over the age of 55 WILL NOT be eligible for vaccination.
Distribution will have the added hurdle of the need to maintain the vaccine at temperatures less than 94 degrees Fahrenheit.
Pfizer projects that they will be able to produce 1.3 billion doses by the end of 2021, able to treat 650 million people WORLD-WIDE. Factories will be distributed in multiple locations across the globe. I know that we would like ALL of the vaccine produced in US factories to be used within the US borders, but we have no corporate control of Pfizer, and I am not sure those of you who think that we should control the vaccine produced here would also support the distribution of all vaccines produced in Belgium to go only to the Belgians. Nor, would you support that vaccines produced in factories in Illinois be constricted to residents of that state first and only to other states once all Illini are vaccinated.
These numbers will be amplified as other vaccines come on board. There will be several vaccines on the market; you will get one or the other, but probably with little choice on your part.