Misguided Decision by FDA Advisory Committee on COVID Booster Shots - Nick Landekic
Sunday, September 19, 2021
The FDA Advisory Committee on Vaccines and Biological Products met on Friday, September 17 to consider an application from Pfizer to allow a third, ‘booster’ dose of its COVID vaccine (Comirnaty). As was reported here, the Committee recommended against a third shot for most people, though voted in favor of third doses for those over 65 and individuals “at high risk of infection.”
This decision was a significant error and exposes Americans to greater suffering.
There was a great deal of detailed discussion and charged debate during the day-long meeting. Clinical trials are complicated, and analyzing the results often not straightforward. All scientific studies have limitations. To conduct the perfect study that would unequivocally answer all imaginable questions would take forever and cost an impossible amount of money. We live in an imperfect world. All clinical data must be carefully evaluated, but decisions need to be made with the information at hand and on the totality of the collective evidence. It can be a fine line between acting rashly and prematurely, and losing sight of the forest by obsessing over a tree.
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1. The Latest Science
Israel has emerged as the undeniable world leader in conducting large, fast, comprehensive clinical studies with COVID vaccines in the pandemic. Many of the emerging clinical observations on vaccines are coming from Israel. This is due to a combination of their high levels of scientific expertise, an effective national health care system that covers and allows analyzing results from their entire population, and a social commitment to protecting the health and lives of their people their highest priority (in comparison, in the U.S. we only have one of those three factors).
Several recent clinical studies from Israel have clearly documented the waning protection of the Pfizer COVID vaccine, and the benefit of third doses. Israel has one of the highest vaccination rates in the world, and to date has given third doses to about 2.8 million people and has made them available to everyone over age 12.
Last week a study in the New England Journal of Medicine, in 1.1 million people over age 60, showed that a third vaccine dose reduced the risk of infection 11.3-fold, and reduced the risk of severe illness 19.5-fold.
Another study of 2.5 million members of a healthcare service in Israel found a 70-84% reduction in the chances of getting infected 14-20 days after receiving a third vaccine dose.
Israel successfully contained the first two surges of the pandemic with their aggressive vaccination program combined with other safety measures, and achieved a more than 100-fold reduction in infections. Unfortunately, the Delta variant is a completely different and much more serious threat, and caused a third surge, similar to what we are experiencing in the U.S.
Studies by the Centers for Disease Control have corroborated the same findings as have been seen in Israel (which is not surprising – the laws of biology and chemistry are the same everywhere). A report this week using the new standard of preventing hospitalization found that Pfizer vaccine effectiveness declined from 91% in the first four months to 77% after four months (the Moderna vaccine maintained the same level of protection of 93% to 92%). While the drop from 91% to 77% might still sound like ‘good’ protection, it is a nearly 3-fold increase in hospitalization and failure rate, from 9% to 23%. This suggests that nearly ¼ of those who received the Pfizer vaccine and subsequently become infected beyond four months could end up hospitalized for COVID.
Another CDC study this week showed that 18% of COVID cases, 14% of hospitalizations, and 16% of deaths, are now occurring in fully vaccinated people. This is a substantial increase from the 5%-8% infection, hospitalization, and death rates seen just two months before. This is additional real-world evidence of diminishing vaccine protection.
All of this does not mean the vaccines aren’t working. They work very well. It’s simply that the human body does not have a long-lasting response to vaccination against the SARS-CoV-2 virus, and it needs to be augmented if we want to continue to prevent infection.
The booster doses are working to contain the pandemic in Israel. Recent reports show that the pandemic is now contracting, with a R value = 0.83 (a R of less than 1 means the number of people being infected is diminishing. By comparison in Rhode Island the R currently = 1.11, meaning the pandemic is still growing exponentially.
This FDA Advisory Committee meeting was unusual in that representatives of the Israel Ministry of Health made an extensive presentation of their experiences with booster doses.
Booster doses in Israel have shown similar benefits for younger age groups with dramatic decreases in COVID infections as was just published in the New England Journal of Medicine for those over 60. The results in Israel are clear: booster doses are significantly reducing COVID infections in those who receive them
Just as important as protection is safety. Israel’s experience with 2.8 million booster doses given so far has been that adverse events have been comparable to less than those seen with the first and second shots of the vaccine.
Safety of any drug is crucially important. A cure cannot be worse than the disease. There have been questions about possible myocarditis, an inflammation of the heart muscle, following the Pfizer COVID vaccine. It’s appropriate for the Advisory Committee to consider this. However, out of 2.8 million booster doses in Israel, there was only one reported case. Myocarditis is far more common from COVID infection than a risk with the vaccine.
2. Changing the Standards
There has been an important change in how some regulators and advisors are evaluating vaccines in the U.S. Previously the standard was ‘prevention of infection’. Recently it has moved to ‘preventing severe illness, hospitalization, or death’. It’s been widely reported and even appeared in the FDA briefing documents for the Advisory Committee meeting that “Data indicate that currently US-licensed or authorized COVID-19 vaccines still afford protection against severe COVID-19 disease and death in the United States.”
This is missing the point, and setting the bar too low. There can be a wide range of experiences with what might be called ‘moderate disease’. Having ‘mild’ COVID can still be a long, painful, and difficult illness.
Even having a ‘mild’ acute case of COVID brings the risk of long-term health problems https://www.hopkinsmedicine.org/health/conditions-and-diseases/coronavirus/covid-long-haulers-long-term-effects-of-covid19. Several studies now suggest than about 1/3 of people who have COVID experience long-term health problems. Alarmingly, this incidence of long-term problems is the same regardless of the severity of the acute course of COVID, even in those who have a ‘mild’ case.
To put long COVID problems in perspective, a recent study showed that long COVID is worse than having cancer.
By setting the bar lower, regulators are exposing far more people to both infection and the risk of long-term health problems. What might seem like a modest decline in vaccine effectiveness can mean a huge relative increase in infections and hospitalizations.
As was presented by the Israel MOH, both 97% and 85% ‘effectiveness’ seem like and could be called ‘good protection’. However, the difference means a 5-fold change in the number of hospitalizations, from 3% to 15% of cases. Across an entire population, that can mean a huge increase in not just hospitalization but also long COVID problems.
Furthermore, ‘hospitalization’ may no longer be an appropriate standard in this country. As hospitals become increasingly overcrowded and people are turned away, patients may be sent home who would otherwise be hospitalized if there were beds available. It’s possible that someone with COVID may be forced to stay at home and have a rough time of it, but still be considered a ‘success’ because they were not ‘hospitalized’.
The regulators are not doing us any favors by lowering the standard from ‘preventing infection’ to ‘protecting against severe illness, hospitalization, or death’.
3. They’re Not Really “Booster” Doses
A better way to think of a third dose of a COVID vaccine might be not so much as a ‘booster’ but simply the way the vaccine should be given.
Most vaccines require more than one dose, most notably the flu vaccine that requires an annual shot.
This is how the human body works. It usually takes more than one exposure to an antigen for our immune system to respond robustly. Several months or more separates most vaccine doses. Our bodies have a stronger response when presented with vaccines spaced apart.
A tremendous amount of effort and money went into developing COVID vaccines. Given the typical high failure rate of new drugs, it is amazing the first attempts worked out so well. One thing that could not be optimized in the short time we had was the best dosing schedule. The Pfizer and Moderna vaccines are dosed 3-4 weeks apart in a desperate attempt to build protection as quickly as possible in the face of a devastating pandemic, but the available evidence suggests more time between doses works better.
If we had the time, the vaccines may have been dosed months apart from the start. The third dose being considered now maybe what would have always been a better way to give the vaccines.
4. Denying Americans Third Shots Will Not Vaccinate Africa
There have been arguments recently that vaccine supplies would save more lives if given to people in poorer countries that have not yet been vaccinated at all instead of as booster shots in developed nations.
This is a false equivalence. Not giving booster shots to Americans will not help vaccinate Africa or South America.
It’s absolutely true that vaccines were in limited supply at the beginning of this year. That is no longer the case. Vaccine supplies now exceed demand.
COVID vaccine doses in the U.S. are expiring before they can be used. In the U.S. at least 15 million doses have been thrown away so far, with millions more doses expiring in the months to come.
There are many hurdles other than supply slowing down vaccination in poorer countries, including:
- Money, the ability to pay for not only vaccines but basic healthcare (though many developed nations and organizations are providing financial support).
- Limited access to laboratories for COVID testing.
- Storage infrastructure – the mRNA vaccines require specialized, expensive ultra-cold freezers. Even electricity is limited in many countries to simply power such freezers.
- Vaccine hesitancy for many reasons https://www.thinkglobalhealth.org/article/vaccine-hesitancy-escalating-danger-africa,
including religious beliefs, lack of familiarity with modern medicine or experience with vaccination in general, lack of trust in governments, and negative perceptions of Western medicine. In Niger and Liberia, 90% of people surveyed believe that prayer is more effective than vaccination https://afrobarometer.org/sites/default/files/publications/Dispatches/ad432-covid-19_vaccine_hesitancy_high_trust_low_in_west_africa-afrobarometer-8march21.pdf.
- Not enough healthcare workers and clinics to administer vaccines on a large scale.
- Limited healthcare regulatory capabilities.
- Poor communications infrastructure to reach and inform people.
- Political instability.
Even when some countries have received grants of large numbers of vaccines, they have not been able to distribute them ut. When offered vaccines, many people in Africa have refused them (sound familiar)?
Nearly 6 billion COVID vaccine doses have been administered to date
A global war-scale effort and multi-national public process is needed to tackle the many real reasons vaccination has been limited in poorer countries and insure that everyone in the world gets vaccinated. But supply is no longer the rate-limiting factor. Denying needed booster shots to Americans will not in any way help poor nations.
The Advisory Committee members and authors of a recent letter in The Lancet are all extremely intelligent, well-educated professionals in their fields. But they seem to lack awareness of the realities of global drug distribution, and the actual reasons holding back vaccinations in the third world. They may be well-intentioned, but also hopelessly naïve and woefully misinformed. No one will be helped, and their misguided actions will only serve to cause more infections and deaths in the U.S.
5. What this Means
The politicization of COVID vaccines is now complete. First the political right politicized vaccination as a rallying cry, with refusal a suicidal badge of honor. Now the political left has also politicized vaccination with the misbegotten effort to deny booster shots in the U.S. in the mistaken belief it would speed vaccination in the third world.
As a country we’ve accepted high community infection rates and COVID deaths as a new normal. We are largely unwilling to take basic safety measures such as wearing masks and social distancing (don’t even mention the dreaded ‘lockdown’). As a society we have placed all our bets on vaccines (for those willing to take them), even though many experts and scientific studies have shown that vaccination alone will not stop the pandemic or the continued rise of variants.
Since we have placed all our stakes on vaccines, shouldn’t we use them as assertively as possible to combat one of the most serious health dangers the world has ever faced?
We are about to pass an ominous landmark: more people will have died of COVID than the 1918 Spanish flu https://fortune.com/2021/09/16/covid-19-deadliest-pandemic-spanish-flu/. That is not a milestone to celebrate.
In addition to recommending third shots for those over 65, the Advisory Committee also recommended them for people “at high risk of infection”, without specific elaboration. It was discussed that healthcare workers, teachers, and those with medical conditions predisposing them to a poor outcome would be ‘at high risk of infection’, but none of these were included in their final vote.
News flash for the Advisory Committee: in the U.S., we are all at high risk of infection.
The U.S. is now reporting the most new COVID cases and deaths every day in the world. Since the pandemic started, the U.S. has reported the most total cases and the most total deaths of any country on Earth. Putting aside any delusions about ‘American exceptionalism’, we have shown ourselves to be truly exceptional at allowing massive numbers of COVID infections and deaths.
In a place like this, at a time like this, under these conditions, aren’t we all at a high risk of infection? If the Advisory Committee agrees that vaccine protection declines over time, and that healthcare workers and teachers could benefit from enhancing their immunity, since supply is not limited shouldn’t everyone have a chance to stay healthy, and alive?
The SARS-CoV-2 virus has outsmarted, outwitted, and outrun us every step of the way. The only sane way to deal with a catastrophe of this magnitude is to stay ahead of it, as Israel is committed to doing, not playing catch up. The Advisory Committee would have us play catch up, a strategy that will only cost more lives than necessary. The vaccine supply is available, and proven to be both effective and safe as third doses. Wouldn’t it be smarter to put it in people’s arms instead of trash dumpsters?
‘Hope for the best’ is not a viable plan when dealing with a deadly foe like the SARS-CoV-2 virus. Nonetheless, at this point let’s hope the FDA reviewers who will likely be meeting next week to consider the Advisory Committee’s recommendations will base their decisions on scientific facts and not politics and egos. Our lives literally depend on it.
Nick Landekic is a retired scientist and biotechnology executive with over 35 years of experience in the pharmaceutical industry.
Editor's Note: This story was updated at 9:15 AM
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