VACCINE TESTING
Today’s news that Russia has “approved” a COVID-19 vaccine is troubling. As I had mentioned in my essay last week, I had expected this announcement, but not for another few weeks. I expect China will follow on shortly.
The scary part of the announcement is how our country may react to this event. As a further act of rubbing the US’s nose in the mud, Russia has called their new vaccine “Sputnik”.
So, let’s look at where we are with Moderna’s vaccine, which is more advanced in the process than any of the other candidates. The arithmetic is clear, although it may not fit will with political goals.
On July 27th Moderna announced that they were ready to begin Phase III trials. These trials would include 30,000 people in a double blind, placebo-controlled test of their new vaccine.
As of today, Moderna has enrolled approximately 7,000 people into their trial, and hope to have it fully enrolled by the end of September. You might ask, “why does it take so long? Lots of people want to help out.” Recruiting into a clinical trial is not simply opening a door and processing a waiting line of applicants. There is quite a lot of work needed to approve someone for a trial.
Let’s look at a few of those issues.
Each volunteer needs to be screened to make sure that they don’t have the virus and haven’t had prior exposure that may have resulted in antibodies in their system.
The population of enrolled people needs to be representative of the population regarding race, age, health conditions, etc. These parameters are predetermined by the test protocols. For example, the test may be restricted to people between the ages of 18 and 55, or to people who have no signs of underlying medical conditions that might increase their potential risks to vaccination. Not only do you want to screen out certain groups of people, but you also want to make sure that the distribution of parameters is appropriate. For example, you don’t want your study consisting of 90% of people over the age of 45, or 90% of people under the age of 45.
The enrolled population has to be appropriately educated and informed that they are participating in a trial in which 50% of the people will be receiving placebos. Therefore, they are potentially still at risk for infection, and death. No one should assume that by being in these trials, that they are in any way protected over the rest of the population.
The population enrolled must be in areas in which they will be exposed to virus. If there is no virus present in the area, there can be no measurement of the effectiveness of the vaccine.
The volunteers must agree to and be willing to be tested on an ongoing basis to determine if they have been infected or have begun an immune response.
The volunteers must also agree to and be judged to be capable of providing ongoing feedback to the study organizers. The recruiters need to have a high degree of confidence that these people WILL remain attentive to the study through the entire duration of the test.
Recruiting, signing, educating and characterizing a group of 30,000 people is not a simple task. Moderna needs to open around 60 centers across the country and they have not completed a large fraction of that yet. It is, therefore, optimistic that they will complete enrollment by the end of SEPTEMBER as they have said.
Assuming that they have completed enrollment by the end of September, they will have a full Phase III in process. The Moderna protocol requires a first vaccination followed 28 days later with a booster. So, the final booster for these enrollees will occur by the end of OCTOBER.
Immune responses are expected to rise to appropriate levels between 14 and 28 days after the second vaccination, so we can expect that by the end of NOVEMBER the enrolled population will be ready to be studied for exposure risk and response.
At that point it is possible to begin to look at potential infections.
We know that it takes between 5 and 14 days after infection for the first symptoms to appear among those people who are not asymptomatic. It then takes at least an additional week before any of those begin to appear at hospitals, and another 1-2 weeks before you see the first deaths. So, adding those together it is at least a month after the immunization has resulted in an antibody response before you will even begin to see concrete statistics, taking us to the end of DECEMBER.
Generally, it takes about 3 months of observations, tracking, testing and data compilation in order to develop the statistical metrics to determined how effective the immunization was in preventing infection in that population, and most importantly, what initial adverse events have been observed. That takes us well into the first quarter of 2021.
Vaccination of that section of the population may begin, but this initial group WILL NOT include children; it will not include the elderly; it will not include the immune-compromised; it will not include the high-risk populations. Those studies will need to be completed AFTER these studies are complete before vaccination of the entire population can occur.
Long-term safety studies will also be necessary to better determine side effects.
The bottom line is that if we follow the most basic safety/efficacy standards for virus vaccines, we will simply not have a vaccine that is approved for use for even a portion of the US population before at least MARCH of 2021. This is not an issue of red tape, over-regulating or lack of effort. It is simply an issue of the fact that time is an inflexible parameter.
We may succumb to the upcoming pressure to follow the lead of Russia and China and make our vaccines available before any of these trials are complete. This would undercut the CDC, the FDA, the NIAID and all prior vaccine investigations. The vaccine might work. But it also might not work, and it might not be safe. If we follow the unfortunate political pattern seen in the southern states after the CDC issued guidelines for reopening in June, a pattern of taking the recommendations as a full-fledged permission slip to open everything up completely without meeting the metrics of the recommendations, we expose ourselves to similar longer term problems, for if a prematurely released vaccine does not result in protection, or if it results in some serious side effects, we will need to take it off the market and risk a situation in which the public no longer trusts any vaccine that is released.