Is the 3rd Moderna vaccine/ booster an emergency for people who have already had 2 doses?
When do we move past EUA and use traditional (BLA) approval?
When it comes to drugs, the FDA has the option of granting accelerated approval. This pathway allows drug products to come to the US market without proving they help people live longer or better, but solely based on augmenting a biomarker thought “reasonably likely” to predict one of those two things.
Accelerated approval is limited to conditions which have “unmet medical need.” But what precisely is an “unmet medical need”? Previously, led by Eric Lu, we found that academics use the term unmet medical need indiscriminately in cancer medicine. Yes, the term referred to conditions that were rare, dire, and had few treatment options, but at other times, the term was used to describe situations that were common, indolent, and had a plethora of options. How can that be an unmet need?
Even “reasonably likely” has been expanded. Recently amyloid levels in the brain have been used to support accelerated approval for Alzheimer’s disease, despite prior FDA guidance saying this endpoint was not reasonably likely to predict improvements in function. The drug in question was aducanumab—it will cost society billions, but is also one where no one has any idea if patients live longer or better by using it.
In short, accelerated approval has been abused.
Now, let’s turn to the COVID19 pandemic. When it comes to granting permission to use vaccine products, the FDA has two options—the traditional approval process, and the Emergency Use Authorization. Here is how the EUA is defined:
FDA may authorize unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions caused by CBRN threat agents when certain criteria are met, including there are no adequate, approved, and available alternatives.
[CRBN stands for chemical, biological, radiological, and nuclear]
Furthermore, FDA notes:
On February 4, 2020, the HHS Secretary determined that there is a public health emergency that has a significant potential to affect national security or the health and security of United States citizens living abroad, and that involves the virus that causes COVID-19.
All that sounds good to me, and I was a vocal supporter of the original vaccine EUAs. Moreover, in these trials the sponsor showed the product reduced symptomatic disease—a higher bar for evidence than showing merely improvement antibody titers. Yet, currently, the FDA is advancing the EUA authority. Specifically, this pathway was used for the Pfizer booster, and is poised, after the advisory vote, to be used for the Moderna booster.
This raises the question: In a world where getting the first dose to all eligible adults remains far from a reality (PS: we must vaccinate all adults who desire vaccination, globally ASAP), is it justified to claim that a 50 microgram booster of Moderna vaccine is warranted for a 24 year old health care worker, who already had two 100 microgram doses of Moderna, under the auspices of an EUA?
COVID19 remains an emergency for the unvaccinated, but is COVID19 an emergency among the vaccinated? Particularly among young people who have already gotten 2 doses of Moderna (the vaccine dose and schedule that continues to retain the highest vaccine effectiveness numbers in real world studies against severe disease)?
Obviously, the same regulatory trade-off is present as with accelerated approval. EUA allows the sponsor to bring the product to market with less certainty about benefits and more uncertainty about harms. In this case, we know with certainty is that a third dose improves antibody titers. But we don’t know about slowing transmission. We don’t know about reducing severe disease.
My last question is this: When will EUA authority end? Will annual boosters attempt to come to market via EUA?
The core question of drug and vaccine products remain: If drugs and vaccines make people live longer or better with side effects that do not offset gains—their approval is a given. I celebrate those products. Moreover, that is a logically defensible bar.
But if we permit products with less and less evidence to come to the market what justifies that? I believe exigent times and desperate circumstances do. The original vaccine series clearly was an emergency. The Moderna booster for a 20 year old health care worker (which is included as the topic of current EUA) pushes EUAs to the limit.
Some claim that EUA needed to curb spread in high risk areas/ locations/ settings; Yet, that hypothesis has not been explicitly tested. All you know is titers are higher for some period of time. A different study design is needed to shed light on that Q.
Most physicians and much of the mainstream media are keen to approve of experimental treatments from multinational pharmaceutical companies, with governments jumping quickly to purchase the products. First it was vaccines and now various IV administered monoclonal antibodies and the potentially mutagenic https://www.inquirer.com/health/coronavirus/merck-covid-pill-fda-molnupiravir-dna-mutations-20211014.html viral RNA replication disruptor molnupiravir. Days after molnupiravir was announced, and before even the FDA or any other national regulatory agency gave any kind of approval for it, the Australian government ordered 300,000 treatment courses at about USD$700 each.
This global push for universal adoption (above some ever-lower age limit) of complex, invasive, months to administer, poorly researched vaccines, to the exclusion of vitamin D supplementation and other early treatments, is widely supported to the point of suppressing discussion and prescription of early treatments, including melatonin, ivermectin, quercetin and, most crucially, vitamin D (bolus D3 or calcifediol to boost levels in a few hours): https://c19early.com .
Even if the current vaccines are as safe and effective as their proponents insist, it is a mistake to portray current infections, harm and deaths as "the pandemic of the unvaccinated". This is the pandemic of the vitamin D deficient and of those who have not been able to receive early treatment. Vaccines run a poor third after vitamin D repletion (first) and multiple early treatments (joint second) in how best to suppress the pandemic.
Most physicians and immunologists have no idea that the immune system needs at least 50ng/ml 125nmol/L circulating 25-hydroxyvitamin D to mount strong innate and adaptive responses to bacterial pathogens. This is 2 to 10 times the levels most people have, without D3 supplementation or recent UV-B skin exposure. It is impossible to overstate the magnitude of this global disaster of billions of people, so under-supplied with the 25-hydroxyvitamin D they need, facing this virus with only slow to administer, expensive, narrow and rapidly declining vaccine-induced immunity with the next stop hospital treatment once hypoxia sets in. (Monoclonal antibodies are also being deployed on an outpatient basis, but it would be much better to get the patients' immune system working properly with bolus D3 or calcifediol, which _is_ 25-hydroxyvitamin D and so goes straight into circulation, without the need for hydroxylation in the liver over several days.)
The fundamental problem driving this lack of awareness about vitamin D and the immune system seems to be that most physicians simply cannot imagine that something so simple could be so important. This pattern of groupthink has been a catastrophic mistake, with the millions harmed and dead from COVID being the tip of an iceberg which includes millions of deaths from sepsis and other inflammatory disorders.
Most physician's are resistant to reading the research which clearly describes the mechanisms by which 25-hydroxyvitamin D enables individual immune cells to respond to their changing circumstances (autocrine and paracrine signaling) and to reduce inflammation, such as by enabling Th1 regulatory lymphocytes to transition from their pro-inflammatory startup program to their anti-inflammatory shutdown program, in response to a high level of a complement protein. McGregor et al. 2020 (link and summary: https://aminotheory.com/cv19/icu/#2020-McGregor) found that Th1 cells from the lungs of hospitalised COVID-19 patients can't transition, because their vitamin D based autocrine signaling system is not working, solely because they lack sufficient 25-hydroxyvitamin D.
Please read the most pertinent research articles, which are cited and summarised at "What every MD, immunologist, virologist and epidemiologist should know about vitamin D and the immune system": https://vitamindstopscovid.info/05-mds/
The crucial nutrient almost everyone is deficient in, which is required for good health and for suppressing COVID-19 severity, viral shedding and transmission, is sitting on the supermarket shelf. It has been ignored by most physicians for far too long. Since 2008 physicians and researchers (some are both) have been urging 40 to 60ng/ml to be recognised as the threshold of 25-hydroxyvitamin D repletion, rather than the 20ng/ml or 30ng/ml standards which are officially accepted: https://www.grassrootshealth.net/project/our-scientists/
We are in the midst of an unprecedented global health disaster, with experts, health professionals and lay people debating vaccines vs. lockdowns. Many people can't believe that so much suffering, harm and death could be caused by the lack of something so simple, safe, inexpensive (unprofitable) and easily available as vitamin D. They should read the research.
If the multinational pharmaceutical companies could patent something half as effective as vitamin D, they would sell it for hundreds or thousands of dollars per month of continual treatment. D3 is made in a handful of specialised factories (UV-B irradiation of 7-dehydrocholesterol, derived with some difficulty from wool fat) - none of them owned by big pharma companies. Most of this D3 goes to agricultural animals who live indoors (as do most humans). For 70kg 154lb bodyweight, 0.125mg (5000IU) D3 a day will, on average, raise circulating 25-hydroxyvitamin D levels safely over 50ng/ml after two or three months. This is a gram every 22 years, and pharma grade D3 sells for USD$2.50 a gram, in 1kg lots, ex-factory.