Based primarily from preliminary data from a substantial study led by Center for Disease Control and Prevention (CDC) researchers, known as the CDC COVID-19 Response v-safe COVID-19 Pregnancy Registry Team, a particular group of scientists in this particular government agency now declare that it’s safe for pregnant women to get the COVID-19 vaccine. With this guidance in place, many expect the vaccination of expecting mothers to commence. The study was published recently in the New England Journal of Medicine (NEJM) and suggests that Pfizer/BioNTech and Moderna’s vaccine products, still considered investigational as they are classified under Emergency Use Authorization (EUA), are in fact safe for pregnant women. TrialSite shares some other research with positive indications as well as formal clinical trials underway. We conclude that as with even formally approved pharmaceutical products, risk is always a factor. Under EUA and the PREP Act, during the pandemic, nearly all consumer protections are banished except for the most egregious of provable actions. TrialSite ponders for healthcare leaders and lawmakers when it’s contemplated that the current COVID-19 vaccines will be transferred from EUA to formal approved status.
Concerns & Questions
Many pregnant women have been in a quandary, concerned that they (and baby) are at risk. Should they get vaccinated or not? While the CDC implied that it was safe, emphasizing that the decision was up to any well-informed physician and consenting patient, as did other medical societies, such as the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine, as recently reported by Sarah Toy and Talal Ansari via the Wall Street Journal.
CDC Study Very Preliminary
A key underlying goal of the CDC study was to better understand the risk of mRNA-based COVID-19 vaccines to pregnant women. While the CDC was aware that people that fell in this cohort were in fact getting vaccines, they had no data on the safety aspects.
So a large team out of the CDC utilized a few different databases to better understand what was happening in the real world, including 1) the v-safe after vaccination health checker surveillances system, 2) the v-safe pregnancy registry, and 3) the Vaccine Adverse Event Reporting System (VAERS) to better understand the safety dynamics associated with the vaccines in relation to pregnant women.
The CDC research team found 35,691 people in the v-safe participant database that were aged 16-54 and classified as pregnant. They found a number of reported response symptoms from muscle pain at jab site to myalgia, chills and some reports of fever. While in the v-safe pregnancy registry with 3,958 enrollees, 827 had a completed pregnancy with 115 (13.9%) indicating a pregnancy loss and 712 (86.1%) resulting in a live birth. They found that adverse neonatal outcomes included preterm birth (9.4%) and small size for gestational age (3.2%) while no neonatal deaths were reported.
While the CDC acknowledges this data is “not directly comparable,” they found that the rations of adverse pregnancy and neonatal outcomes in those individuals receiving the mRNA-based jabs and who also were classified as having a completed pregnancy were in fact similar to actual incidents reported in studies involving pregnant women that occurred before the COVID-19 pandemic even started. So, for example, out of the 221 pregnancy-related adverse events reported in VAERS, the most commonly reported event happened to be a spontaneous abortion. Their point, although not scientifically comparable, is that this is similar to non-COVID population.
So the CDC summarizes that the preliminary findings preclude any “obvious safety signals among pregnant persons who received mRNA-COVID-19 vaccines.” The group noted importantly that “more longitudinal follow-up,” such as the study of “large numbers of women vaccinated earlier in pregnancy” should be conducted to better “inform maternal, pregnancy and infant outcome.”
Another Small Study Indicates Positive Results
In another study published in the American Journal of Obstetrics Gynecology, a group of researchers performed a prospective cohort study at two academic medical centers involving 131 participants (84 pregnant women, 31 lactating and 16 non-pregnant women.) This study found that the three cohorts all responded well to the vaccine and that there were no material differences in vaccine-induced side effects between pregnant and non-pregnant women.
Moderna Official Stance: Not Sufficient Data to Know
First TrialSite reminds that the mRNA-1273 vaccine still is considered investigational as it is authorized under EUA. Moderna in an April 13 investor press release, among other things, addressed the topic of vaccine administration in pregnant women. Under “Important Safety Information,” the company informed investors that the “Available data on Moderna COVID-19 Vaccine administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy. Data are not available to assess the effects of Moderna COVID-19 Vaccine on the breast fed infant or on milk production/excretion.”
Of course, this investor press information was released before the CDC study but the CDC study is based on observational data that carries less evidentiary weight.
Clinical Trial Example
Pfizer/BioNTech announced back in February that the first participants were dosed in a clinical trial evaluating the safety, tolerability and immunogenicity of the mRNA-based BNT162b2 COVID-19 vaccine in healthy pregnant women.
This randomized, placebo-controlled, observer-blind Phase 2/3 clinical trial (NCT04754594) involves approximately 4,000 healthy pregnant women aged 18 and up vaccinated during 24 to 34 weeks of gestation. The study investigates the safety and tolerability, as well as immunogenicity, of two doses of the vaccine or placebo administered 21 days apart. The women will be monitored for up to 10 months and also assess the safety in infants of vaccinated women. Under inquiry is the possibility that the antibody will transfer to the infants. These infants will be monitored until approximately six months of age.
This large study is conducted at over 80 trial site centers.
What does Emergency Use Mean?
Both the Pfizer and Moderna vaccines haven’t yet been formally approved by the FDA. Rather, they remain under EUA as the government authority (FDA) has deemed the risks associated with the lack of vaccination are greater than the risks associated with vaccination or the investigational mRNA-based products during this pandemic thus far. Authorized under emergency use for those 16 and above, this authorization lasts only as long as the declaration is justified under Section 564 (b) (1) of the FD&C Act unless terminated or revoked sooner. More information from the FDA on the EUA is offered.
What products can the FDA authorize under EUA? For the pandemic, the FDA has demonstrated that, first and foremost, a “serious or life-threatening” disease or condition is one that threatens the public. Second, they must demonstrate actual “evidence” for efficacy; third, they must perform a risk-based analysis: that is the “known and potential benefits of the product” as is the case of vaccines when used in the prevention of COVID-19, “outweigh the known and potential risks of the product.” In making this determination, the FDA delves into the “totality of the scientific evidence” in their quest to generate the defining “risk-benefit determination.” Finally, there is a provision in the law that there are “no alternatives,” or a product that is either “adequate, approved,” and “available” and serves as an alternative to the vaccine.
What other risks are involved with Emergency Use Vaccines?
There are a number of risks to people in any EUA. Under EUA, the agency although expecting manufacturers to comply with standard regulatory production requirements, such as Good Clinical Practices and Good Manufacturing Practices (GcP, GmP), under the EUA law waivers can be granted in the EUA on case-by-case basis. Moreover, under EUA, normal prescription law can be waived. For example, mass vaccination centers can be considered “points of dispensing” (PODs) and in these situations, when not practicable for each person to interact with a licensed medical practitioner, other personnel could feasibly step in and administer the vaccine.
What about the PREP Act & Liability for EUA/other pandemic products?
With the onset of the pandemic, the U.S. government via the Secretary of HHS issued a public health information declaration to be effective back on February 4, 2020. This declaration was meant to trigger a number of liability immunity clauses under the Public Health and Emergency Preparedness Act (PREP-Act). Now with this provision in place, those products that are deemed “qualified pandemic products” are in fact “immune from suit and liability under federal and state law with respect to all claims for loss caused by, arising out of, relating to, or resulting from the administration to or use an individual of a covered countermeasure if a Declaration has been issued with respect to such countermeasure.” Interestingly, PREP Act protections aren’t conditioned on other emergency act declarations.
Importantly, products such as the vaccines that were not approved or in hopes of a label expansion for new indication still are subjected to the regulatory processes to fall in line with the PREP and must still follow regulatory guidelines, such as those of the FDA.
While there are liability exceptions, that is situations that can trigger liability for vaccine makers, it’s not what the standard healthcare consumer may think. The immunity from liability is a powerful risk mitigator for the vaccine producer.
So what exceptions are there? Well, if death or serious injury occurs due to the “willful misconduct” of the vaccine maker then the exception can apply assuming the aggrieved party can actually prove “willful misconduct,” which is inordinately difficult to do. For example, the ACT declares, “Willful misconduct is misconduct that is greater than any form of recklessness or negligence.” More specifically, a list of conditions can be reviewed here.
Call to Action: The general consensus of government, industry and medical academia is that the risks of not taking the investigational COVID-19 vaccine is greater than the risks of not doing so—that is, the risk of infection with SARS-CoV-2, especially with a growing number of mutant variants, is higher than the risk of an adverse affect from vaccination. The data thus far backs this claim. Beside the known adverse event issues, there have been some deaths reported that are seemingly too close to the vaccination event for comfort. They are explained away as typically associated with something else. Nonetheless, the probabilities of adverse issues remain extremely low. Fundamental assumptions in the mass vaccination program are that the vaccines, which are designed to protect against the spike protein, won’t be materially impacted by mutation or other elements of the original SARS-COV-2. But it’s very possible that the current situation will evolve into an ongoing mass vaccination program with jabs every couple years and boosters. One question TrialSite poses to healthcare leaders, policy and lawmakers is “when will we move to make these products formally approved and thus registered with a full FDA label—that is, transition out of the zone of nearly complete immunity protection for the producers?” America’s legal system, although some bash as litigious, actually represents a powerful, tried and true way to ensure markets operate fairly and that regulatory capture and other dynamics associated with crony-capitalism don’t overwhelmingly bias the system. Food for thought.