Covid-19 vaccinations – abundance of caution – as it should be

Yesterday I received dose 1 of Pfizer vaccine and later in the day I read that Pfizer is in a position for full FDA approval of the vaccine. https://www.fiercepharma.com/pharma/pfizer-biontech-eye-official-covid-19-vaccine-nod-as-efficacy-stands-strong-including

“The new efficacy data (is 91.3% effective against symptomatic COVID-19), plus a safety analysis comprising data from more than 12,000 people who were fully immunized for at least six months, allow the companies to file a drug application with the FDA to turn the shot’s emergency use authorization into a full approval, Pfizer CEO Albert Bourla, Ph.D., said in a statement.”

My son and daughter-in-law are exposed to a fair amount of vaccine hesitancy and when they ask me to help them answer the concerns, I have struggled to find answers to not unreasonable questions given the confusing language that is being used in various official documents.

The educational information given to individuals receiving the Pfizer-BioNTech vaccine states that the vaccine is unapproved. Technically, the FDA has issued Pfizer-BioNTech, Moderna and J&J authorization for emergency use. I could find no explanation for what it would take to get full FDA approval. For some people hesitant to get a vaccine, full FDA approval is a VERY important milestone. In the context of the rapid development of all of the vaccines some degree of caution is not unreasonable.

While it is not explicitly stated in the article, the FDA required 6 months of efficacy and safety data on a large number of people to consider full approval. At the beginning of the drug development process the FDA tells the companies what data is needed to seek FDA approval. In the circumstance of this pandemic, it was apparently determined that authorization for emergency use would be granted if vaccines demonstrated that they protected against getting Covid-19 with low adverse reactions 7 days after the second vaccination. Emergency use was authorized when the group that received vaccination had 8 COVID-19 cases and 162 COVID-19 cases in the placebo group for 95% efficacy.

The Pfizer-BioNTech vaccine still has excellent efficacy at 6 months – 91% with no signal of any safety concerns in the clinical trial participants or in the millions of vaccinated people. The requirement for 6 month data makes sense for full FDA approval and I am glad 12 month data was not required. Perhaps this type of information is confidential between companies and FDA, but it would have been helpful to know that full FDA approval was possible in the first half of 2021 when enough study participants had been followed for 6 months.

Today, we have news that the J&J one dose vaccine has been put on pause for extremely unusual complication – cerebral venous sinus thrombosis (CVST), that occurred in 6 women (out of 7 million people vaccinated). This is extremely rare. The risk-benefit of this decision is complicated because this one dose vaccine that does not require extreme cold for storage is the easiest to use underserved communities that are most at risk for Covid-19. It is possible that more than 6 people scheduled to get the J&J vaccine will contract and die of Covid during this pause. Is this really the right decision?

My initial reaction was why not just pause in women under 50 years since all of the CVST occurred in women less than 50. However after reflection, I think taking a short pause to make sure there is not significant under-reporting is reasonable. Reporting adverse reactions can be a very time consuming process and is not always done outside of clinical studies.

This pause also allows time for education of ALL clinicians about the diagnosis and treatment for CVST. Given CVST is rare, many clinicians may not know they require a different treatment approach. For me, this is the most compelling reason for the pause. If more clots occur, let’s make sure clinicians can diagnose them quickly, treat them appropriately and report them to the company or FDA.

Both Pfizer-BioNTech and J&J vaccines have excellent safety profiles. J&J was put on pause because of a signal of a safety concern became apparent after it had been used in 7 million people. It will be fully investigated. This demonstrates why the FDA required longer term follow-up before considering full approval.

We are all learning so much about topics we never thought about before March 2020.