**These are just notes.
Click on the following link for the full blog on this meeting: FDA Meeting Highlights: Pfizer vaccine authorized for children 5 - 11 (justfactswithkat.com)
Notes from reading:
SOURCE 2 = Pfizer’s briefing document
SOURCE 3 = FDA’s briefing document
From the FDA’s Briefing Document
SOURCE 3, page 5:
"The most frequently reported unsolicited adverse event (AE) in Cohort 1 BNT162b2 recipients was lymphadenopathy"
*Lymphadenopathy: disease affecting the lymph nodes.; swollen lymph nodes.
SOURCE 3, page 5:
"At the lowest evaluated COVID-19 incidence (corresponding to the June 2021 nadir), the predicted number of vaccine-associated myocarditis cases was greater than the predicted number of COVID-19 hospitalizations prevented for males and for both sexes combined."
This implies that if we succeed at achieving herd immunity, if we can get COVID cases to be as low as they were in June of this year, then a child is more susceptible to vaccine associated myocarditis than severe COVID-19 (with the exception of children at high risk for COVID-19).
In other words, vaccinating children is only beneficial if COVID-19 cases are high.
If COVID-19 cases are low, then vaccinating children is *more risky than beneficial.
*with exception of children with comorbidities; comorbidities discussed in next section
*Comorbidities: underlying health conditions
Children with comorbidities are at a higher risk of severe COVID-19 than children that don't have any underlying health conditions.
SOURCE 3, page 6/7
"The most common underlying medical conditions among hospitalized children were chronic lung disease (29%), obesity (25%) and neurologic disorders (23%). A total of 68% of hospitalized children had more than one underlying condition. Obesity and feeding tube dependence were associated with increased risk of severe disease. Available evidence suggests that highest risk groups include children with special healthcare needs, including genetic, neurologic, metabolic conditions, or with congenital heart disease."
· The highlighted data is presented in the following slide
*This image ( of the slide ) is also in the blog "FDA Meeting Highlights.
SOURCE 3, page 9
"Remdesivir is the only product currently approved by the FDA for treatment of COVID-19 requiring hospitalization, and its approved use is limited to individuals 12 years of age and older. Prior to its approval, remdesivir was authorized for emergency use in adults and pediatric patients and remains authorized for emergency use in hospitalized pediatric patients who are not included in the indicated population under licensure."
Adverse Rxxns:
SOURCE 3, page 13
"In an FDA analysis of the Optum healthcare claims database, the estimated excess risk of myocarditis/pericarditis approached 200 cases per million fully vaccinated males 16-17 years of age and 180 cases per million fully vaccinated males 12-15 years of age.44 Although some cases of vaccine-associated myocarditis/pericarditis have required intensive care support, available data from short-term follow-up suggest that most individuals have had resolution of symptoms with conservative management. Information is not yet available about potential long-term sequelae and outcomes in affected individuals, or whether the vaccine might be associated initially with subclinical myocarditis (and if so, what are the long-term sequelae). Myocarditis and pericarditis were added as important identified risks in the PVP and included in the Warnings sections of the vaccine Fact Sheets and Prescribing Information. The Sponsor is conducting additional post-authorization/post-marketing 14 studies to assess known serious risks of myocarditis and pericarditis as well as to identify an unexpected serious risk of subclinical myocarditis."
For a comparison, about 10 children per million experience severe COVID-19. Thus, children are 15-18x more likely to get vaccine associated myocarditis than severe covid.
SOURCE 3, page 14
"To provide a vaccine with an improved stability profile, the Pfizer-BioNTech COVID-19 Vaccine for use in children 5-11 years of age uses tromethamine (Tris) buffer instead of the phosphatebuffered saline (PBS) as used in the previous formulation and excludes sodium chloride and potassium chloride."
SOURCE 3, page 15
"Regulatory considerations for clinical development of COVID-19 vaccines in children:
The Vaccines and Related Biological Products Advisory Committee convened on June 21, 2021 to discuss, in general, the data needed to support authorization and/or licensure of COVID-19 vaccines for use in pediatric populations."
SOURCE 3, page 15/16
Effectiveness
"The immune marker(s) used for immunobridging do not need to be scientifically established to predict protection but should be clinically relevant to the disease.
Because no specific neutralizing antibody titer has been established to predict protection against COVID-19, two immunogenicity endpoints (geometric mean titer [GMT] and seroresponse rate) are considered appropriate for comparing the range of neutralizing antibody responses elicited by the vaccine in pediatric vs. young adult populations."
The official name of Pfizer’s pediatric study is “C4591007”.
SOURCE 3, page 16 7.1 Overview of study C45910007
“C4591007 (is) an ongoing Phase 1/2/3, randomized, placebo-controlled study. The comparator group for the immunobridging analyses to support vaccine effectiveness in this age group was a random subset of Phase 2/3 participants 16-25 years of age enrolled in study C4591001, the study in which vaccine efficacy against COVID-19 was established in individuals 16 years of age or older."
The OFFICIAL name of the Pfizer vaccine is BNT162b2.
SOURCE 3, page 17
“Phase 2/3: a total of 3,109 BNT162b2 (10 μg) recipients and 1528 placebo recipients 5-11 years of age
– Cohort 1: 1,518 BNT162b2 (10 μg) recipients and 750 placebo recipients, of whom 1,444 (95.1%) and 714 (95.2%), respectively, had at least 2 months of safety follow-up after completing a 2-dose primary series; at the time of this Briefing Document was prepared, FDA has not fully verified the underlying data or Pfizer-BioNTech’s conclusions from this analysis.
– Cohort 2: A second cohort of 1,591 BNT162b2 (10 μg) recipients and 778 placebo recipients had a median duration of follow-up of 2.4 weeks post-Dose 2 at the time of data cutoff (October 8, 2021). Safety data from this cohort were provided for further assessment of SAEs and AEs of clinical interest. Data verification is in process, but not yet finished at the time this briefing book was completed.”
SOURCE 3, page 33
“For this analysis the estimate for ages 12-15 years is applied to ages 5-11 years because vaccine associated myocarditis/pericarditis data is not available for this age group at this moment.”
In other words, because we do not currently have data on myocarditis or pericarditis for children 5-11 years old, Pfizer is assuming that the excess myocarditis/pericarditis from the age group 12-15 will be similar.
Pfizer adds that this assumption may be a conservative overestimate, and you can read the reasons why in the corresponding paragraph (see image above).
From Pfizer’s Briefing Document
**Will update this soon, pictures will be added as well (for last 2 points)
SOURCE 2, page 11
“The number of participants in the current clinical development program is too small to detect any potential risks of myocarditis associated with vaccination."
This is why Pfizer is assuming that the vaccine associated myocarditis rate for 5 - 11 year olds is the same as the rate for 12 - 15 year olds (as mentioned earlier from the FDA's briefing document).
SOURCE 2, page 20
“With <21 cases (protocol specified number for formal evaluation of VE) accrued by the time of this analysis, there is an increased risk of observing by chance a lower VE than the true VE compared to the same risk when ≥21 cases have been accrued.
To inform VRBPAC’s decision on whether to recommend approving the vaccine for this age group, Pfizer has provided the most comprehensive and up-to-date data available, despite the potential risk of a higher ‘type II error’”
More to consider on the “data” for vaccine efficacy.
It was determined that at least 21 children have to get symptomatic COVID-19 in the pediatric study to accurately estimate vaccine efficacy (VE).
Only 19 children in the study got COVID.
Thus, technically there aren’t enough COVID cases in the study to accurately evaluate vaccine efficacy, but it’s pretty close to the minimum (21), and Pfizer included this in their brief as a heads up.
Again, this study is ONGOING, it’s not over yet and we can expect more data soon.
The adult dose of the vaccine is 30-µg.
Adult doses are DANGEROUS for children 5 - 11 !!!
SOURCE 2, page 21
3.4.1. Reactogenicity – Phase 1
“Local Reactions
Local reactions at the 30-µg dose level were deemed unacceptable, leading to the discontinuation of this dose level. With regard to local reactions, the 10 and 20 µg dose levels were the best tolerated.
Systemic Events
Systemic events were mostly mild to moderate and short-lived. Systemic events at the 30-µg dose level were deemed unacceptable, leading to the discontinuation of this dose level. With regard to systemic events, the 10-µg dose level was the best tolerated”
So 30-µg (adult dose) is unacceptable for BOTH local AND systemic reactions.
Children have been reported getting the adult dose of the vaccine by mistake.
I hope it is abundantly clear that a mistake like this can cause severe harm to the child.
Adult vials have purple caps.
Vials for children have orange caps. If you choose to vaccinate your child, MAKE SURE they get a vial with an ORANGE cap!!!
SOURCE 2, page 45
Adverse Events Leading to Withdrawal
“One participant withdrew due to an AE of severe pyrexia with onset of 2 days after Dose 1…
After Dose 1 Day 2 she reported a temperature of 40.1 °C. ( or 104.18 °F );
Participant also had severe neutropenia…
Participant had a medical history of benign transient neutropenia of unknown etiology, gingivitis, and otitis media. Prior to study: baseline absolute neutrophil count (ANC) of 480.
Two days after receiving Dose 1: participant had an ANC of 20.
*ANC = Absolute Neutrophil Count
Neutrophils
on Day 19 after Dose 1, the participant had bleeding gums for 1 week prior.”
No cases of COVID-19 were observed in either the vaccine group or the placebo group in participants with evidence of prior SARS-CoV-2 infection
Does this imply that … that natural immunity works?
the 3 cases reported in the BNT162b2 group occurred at disparate and later times, with 1 case each reported at approximately 1.5 months, 3.5 months, and 4 months after Dose 1.
Does efficacy wane after 4 months?
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