Pfizer's own data point towards an excess of mRNA vaccine harms for those aged 12-25 years
Dear Editor,
Pfizer's own data point towards an excess of mRNA vaccine harms for those aged 12-25 years
In this News Analysis, Jacqui Wise [1] writes about the reports of myocarditis and pericarditis after mRNA vaccines administered in those aged 25 and below. These reports are based on pharmacovigilance systems with known serious limitations [2], where an estimated 9 in 10 serious adverse drug reactions remain unreported, leading to gross underestimation of true harm incidence. One can look instead directly into Pfizer’s own studies on younger individuals to see how serious harms in the vaccinated groups are significantly higher than those in the unvaccinated groups. I give below a brief analysis.
The article by Pfizer’s researchers recently published in the New England Journal of Medicine [3] reports on a single(observer)-blinded, low-powered, short-follow-up randomised controlled trial on a little more than 2,000 children aged 12-15 years. It also contains data from the trial in those aged 16-25 years. This study report has been the basis of the Medicines and Healthcare products Regulatory Agency emergency approval extension of the Pfizer mRNA covid-19 vaccine to adolescent aged 12-15.
Regarding vaccine harms, from the adverse events table dutifully relegated to the supplementary appendix [4] one can extract and compound the serious adverse events data (excluding deaths) for the 12-15 and the 16-25 age group. Sixteen participants of the 1,667 vaccinated had at least one serious adverse event, while only 5 participants of the 1,690 unvaccinated had at least one serious adverse event. This means that those vaccinated had a statistically significant 224% higher risk of severe adverse events than those unvaccinated (risk ratio 3.24, 95% CI 1.19, 8.84), albeit with high imprecision. The absolute risk reduction between groups is 0.66%, which leads to a number needed to treat for an additional harmful outcome (NNTH) of 151, CI 83.4, 775. This was based on only one month follow-up after second vaccination.
Regarding vaccine benefits, the Pfizer’s study reports that in the 12-15 year age group there were 16 covid-19 ‘cases’ in the placebo group, and none in the treatment group, between 7 days and 2 months after second dose. This is a number needed to treat for an additional beneficial outcome (NNTB) of 70. However, the definition of ‘cases’ in the method section of the supplementary material ranged from simple sore throat to death, with a positive covid-19 test. Unfortunately, the report does not tell us how many of the 16 cases were serious ones. Considering the low incidence of serious events after a covid-19 infection in the 12-15 age group, the NNTB for this group is likely much higher than 70. Also, The number of cases in the 16-25 age group are not reported. Hence, it is not possible to calculate from the data in the study the NNTB for the whole 12-25 age group.
However, assuming a 100% efficacious vaccine, the maximum absolute risk of hospitalisation of the 12-25 year age group in one month could be used to estimate the NNTB to prevent serious covid-19 infections. For example, the UK Government commissioned the QCovid risk calculator [5] specifically to this aim. It estimates the individual risk of death or hospitalisation based on demographics and comorbidities, over a 90-day period based on data from the first peak of the pandemic in the UK. For a healthy white male aged 25 years, the absolute risk of hospitalisation is calculated as 0.0089%. Thus, the NNTB for preventing hospitalisation, adjusted to one month to match the study follow-up period, is (1/0.000089)x3 = 3,371, with high precision, as this is based on whole population data. For younger individuals, the NNTB gets progressively higher.
Therefore, the NNTB is estimated to be one order of magnitude higher than the NNTH. In plain English, for every single prevention of a hospital admission, at least 22 to 23 individuals (NNTB/NNTH=22.3) will experience at least one serious adverse event. Even using the upper limit of the NNTH confidence interval, 4 to 5 individuals will experience at least one serious adverse event for each prevented hospital admission.
On this basis, vaccination against covid-19 of those aged 25 and below seems not indicated, as harms far outweigh the benefits. The MHRA should perhaps reconsider their emergency approval in younger adults, for whom there is indeed no covid emergency, and wait for longer follow-up and suitably powered studies. Also, the Joint Committee on Vaccination and Immunisation will hopefully at least refrain to extend the mass vaccination programme to those aged 12-15.
[1] J. Wise, Covid-19 : Should we be worried about reports of myocarditis and pericarditis after mRNA vaccines ? Jacqui Wise looks at the data released by UK and US regulatory agencies this week, (2021) 1–2. https://doi.org/10.1136/bmj.n1635.
[2] M.T. Suadoni, Pharmacovigilance needs improvement (Rapid response to https://doi.org/10.1136/bmj.n931 ), BMJ Rapid Responses. (2021). https://www.bmj.com/content/373/bmj.n931/rr-16.
[3] R.W. Frenck, N.P. Klein, N. Kitchin, A. Gurtman, J. Absalon, S. Lockhart, J.L. Perez, E.B. Walter, S. Senders, R. Bailey, K.A. Swanson, H. Ma, X. Xu, K. Koury, W. V. Kalina, D. Cooper, T. Jennings, D.M. Brandon, S.J. Thomas, Ö. Türeci, D.B. Tresnan, S. Mather, P.R. Dormitzer, U. Şahin, K.U. Jansen, W.C. Gruber, Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents, N. Engl. J. Med. (2021) 1–12. https://doi.org/10.1056/nejmoa2107456.
[4] R.W. Frenck, N.P. Klein, N. Kitchin, A. Gurtman, J. Absalon, S. Lockhart, J.L. Perez, E.B. Walter, S. Senders, R. Bailey, K.A. Swanson, H. Ma, X. Xu, K. Koury, W. V. Kalina, D. Cooper, T. Jennings, D.M. Brandon, S.J. Thomas, Ö. Türeci, D.B. Tresnan, S. Mather, P.R. Dormitzer, U. Şahin, K.U. Jansen, W.C. Gruber, Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents - Supplementary Appendix, N. Engl. J. Med. (2021). https://doi.org/10.1056/nejmoa2107456.
[5] University of Oxford, Welcome to the QCovid® risk calculator, (2021). https://qcovid.org/ (accessed June 28, 2021).
Competing interests:
No competing interests
28 June 2021
Marco T Suadoni
Practice Development Nurse and Vaccination Centre Supervisor
Rapid Response:
Pfizer's own data point towards an excess of mRNA vaccine harms for those aged 12-25 years
Dear Editor,
Pfizer's own data point towards an excess of mRNA vaccine harms for those aged 12-25 years
In this News Analysis, Jacqui Wise [1] writes about the reports of myocarditis and pericarditis after mRNA vaccines administered in those aged 25 and below. These reports are based on pharmacovigilance systems with known serious limitations [2], where an estimated 9 in 10 serious adverse drug reactions remain unreported, leading to gross underestimation of true harm incidence. One can look instead directly into Pfizer’s own studies on younger individuals to see how serious harms in the vaccinated groups are significantly higher than those in the unvaccinated groups. I give below a brief analysis.
The article by Pfizer’s researchers recently published in the New England Journal of Medicine [3] reports on a single(observer)-blinded, low-powered, short-follow-up randomised controlled trial on a little more than 2,000 children aged 12-15 years. It also contains data from the trial in those aged 16-25 years. This study report has been the basis of the Medicines and Healthcare products Regulatory Agency emergency approval extension of the Pfizer mRNA covid-19 vaccine to adolescent aged 12-15.
Regarding vaccine harms, from the adverse events table dutifully relegated to the supplementary appendix [4] one can extract and compound the serious adverse events data (excluding deaths) for the 12-15 and the 16-25 age group. Sixteen participants of the 1,667 vaccinated had at least one serious adverse event, while only 5 participants of the 1,690 unvaccinated had at least one serious adverse event. This means that those vaccinated had a statistically significant 224% higher risk of severe adverse events than those unvaccinated (risk ratio 3.24, 95% CI 1.19, 8.84), albeit with high imprecision. The absolute risk reduction between groups is 0.66%, which leads to a number needed to treat for an additional harmful outcome (NNTH) of 151, CI 83.4, 775. This was based on only one month follow-up after second vaccination.
Regarding vaccine benefits, the Pfizer’s study reports that in the 12-15 year age group there were 16 covid-19 ‘cases’ in the placebo group, and none in the treatment group, between 7 days and 2 months after second dose. This is a number needed to treat for an additional beneficial outcome (NNTB) of 70. However, the definition of ‘cases’ in the method section of the supplementary material ranged from simple sore throat to death, with a positive covid-19 test. Unfortunately, the report does not tell us how many of the 16 cases were serious ones. Considering the low incidence of serious events after a covid-19 infection in the 12-15 age group, the NNTB for this group is likely much higher than 70. Also, The number of cases in the 16-25 age group are not reported. Hence, it is not possible to calculate from the data in the study the NNTB for the whole 12-25 age group.
However, assuming a 100% efficacious vaccine, the maximum absolute risk of hospitalisation of the 12-25 year age group in one month could be used to estimate the NNTB to prevent serious covid-19 infections. For example, the UK Government commissioned the QCovid risk calculator [5] specifically to this aim. It estimates the individual risk of death or hospitalisation based on demographics and comorbidities, over a 90-day period based on data from the first peak of the pandemic in the UK. For a healthy white male aged 25 years, the absolute risk of hospitalisation is calculated as 0.0089%. Thus, the NNTB for preventing hospitalisation, adjusted to one month to match the study follow-up period, is (1/0.000089)x3 = 3,371, with high precision, as this is based on whole population data. For younger individuals, the NNTB gets progressively higher.
Therefore, the NNTB is estimated to be one order of magnitude higher than the NNTH. In plain English, for every single prevention of a hospital admission, at least 22 to 23 individuals (NNTB/NNTH=22.3) will experience at least one serious adverse event. Even using the upper limit of the NNTH confidence interval, 4 to 5 individuals will experience at least one serious adverse event for each prevented hospital admission.
On this basis, vaccination against covid-19 of those aged 25 and below seems not indicated, as harms far outweigh the benefits. The MHRA should perhaps reconsider their emergency approval in younger adults, for whom there is indeed no covid emergency, and wait for longer follow-up and suitably powered studies. Also, the Joint Committee on Vaccination and Immunisation will hopefully at least refrain to extend the mass vaccination programme to those aged 12-15.
marco.suadoni@pm.me
References
[1] J. Wise, Covid-19 : Should we be worried about reports of myocarditis and pericarditis after mRNA vaccines ? Jacqui Wise looks at the data released by UK and US regulatory agencies this week, (2021) 1–2. https://doi.org/10.1136/bmj.n1635.
[2] M.T. Suadoni, Pharmacovigilance needs improvement (Rapid response to https://doi.org/10.1136/bmj.n931 ), BMJ Rapid Responses. (2021). https://www.bmj.com/content/373/bmj.n931/rr-16.
[3] R.W. Frenck, N.P. Klein, N. Kitchin, A. Gurtman, J. Absalon, S. Lockhart, J.L. Perez, E.B. Walter, S. Senders, R. Bailey, K.A. Swanson, H. Ma, X. Xu, K. Koury, W. V. Kalina, D. Cooper, T. Jennings, D.M. Brandon, S.J. Thomas, Ö. Türeci, D.B. Tresnan, S. Mather, P.R. Dormitzer, U. Şahin, K.U. Jansen, W.C. Gruber, Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents, N. Engl. J. Med. (2021) 1–12. https://doi.org/10.1056/nejmoa2107456.
[4] R.W. Frenck, N.P. Klein, N. Kitchin, A. Gurtman, J. Absalon, S. Lockhart, J.L. Perez, E.B. Walter, S. Senders, R. Bailey, K.A. Swanson, H. Ma, X. Xu, K. Koury, W. V. Kalina, D. Cooper, T. Jennings, D.M. Brandon, S.J. Thomas, Ö. Türeci, D.B. Tresnan, S. Mather, P.R. Dormitzer, U. Şahin, K.U. Jansen, W.C. Gruber, Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents - Supplementary Appendix, N. Engl. J. Med. (2021). https://doi.org/10.1056/nejmoa2107456.
[5] University of Oxford, Welcome to the QCovid® risk calculator, (2021). https://qcovid.org/ (accessed June 28, 2021).
Competing interests: No competing interests