II. Design the protocol in a way that will allow the company to present positive findings regarding the safety of the vaccine
In at least two criteria, the company appears to have manipulatively designed the protocol in a way that would allow it to present as positive findings as possible in terms of vaccine safety in children:
A. Designing the protocol in a way that will reduce, as much as possible, the inclusion of severe adverse events in a report submitted to the FDA.
In the Pediatric Study Protocol (see table on page 12), Pfizer undertook that the duration of follow-up for serious adverse events (SAEs) would be “from Dose 1 to 6 months after the second dose”.
A six-month follow-up period is considered to be very short compared to the usual follow-up time in Phase 3 studies for vaccines. According to the FDA, Phase 3 in vaccine studies should last between one and four years.
Yet it turns out from Pfizer’s review document that the company did not complete even this relatively short follow-up period, and in fact was content with only 30 days of follow-up of the severe adverse events. This fact emerges from the chapter dealing with the date of analysis (page 30, under the heading of the SAEs chapter): “12-15-year-olds: SAEs from Dose 1 through up to 30 days after Dose 2 in ongoing follow-up were reported by 0.4% of BNT162b2 recipients and 0.1% of placebo recipients“.
How has this been made possible?
On page 114 of the study protocol – in the chapter dealing with the timing at which the statistical analyzes will be performed, Pfizer set a number of time points for the purpose of performing these analyzes. While the maximum time period for monitoring severe adverse events in the general study population is six months (the seventh section), the fifth section set an additional cut-off point, of only 30 days after the second dose for the purpose of comparing data between two age groups – one of ages 12-15 and one of ages 16-25.
In other words, the protocol appears to be designed in such a way that the review submitted to the FDA will only include the serious adverse events that appeared during the first month after vaccination.
Indeed the follow-up of the serious adverse events continues for another five months, but any adverse event that will be discovered during these months, or an adverse event that was observed during the first month but was defined as non-serious and has been worsening during the following months (or the diagnosis will change) – will simply not appear in the review report.
The concerning implication of this practice is that serious adverse events may not appear in the report on the basis of which the FDA issues the emergency authorization for children, so continued follow-up, even if published a few months or years after the temporary authorization was issued, will not help children who will be harmed or die following the FDA’s green light.
B. Designing the protocol so that diagnoses of serious adverse events given in hospitals unrelated to the study site can be ignored.
Within the terms of the Outcome Measures in the study protocol, as it is presented in Clinicaltrials.gov Pfizer determined that the research team selected by Pfizer will be the ones defining the adverse events as such: “As elicited by investigative site staff”.
This way, the company has in effect given researchers selected by them the power to define for themselves what the diagnosis will be, regardless of the diagnosis given at the hospital/ward which is not defined as the research site.
Why is this problematic?
Because such a determination means that if a particular participant suffers from serious adverse events and has been treated, for example, outside the hospital or ward that functions as the research site, then in fact, the diagnosis made by the attending physicians at the hospital/ward in which the participant is treated is irrelevant.
This way, Pfizer has actually allowed its team to define what the diagnosis will be, rather than letting the diagnosis given by the attending physicians confuse them.
Beyond the severe criticism towards Pfizer, the analysis and comparison raise serious questions for the FDA itself:
* How is it possible that the FDA has even approved a protocol that allows such manipulations?
* Why did the FDA allow the company to perform the data analysis and submit the application for the emergency permit in children after such a short follow-up time of only 30 days?
* What made the FDA so eager to approve the emergency permit for children? Why is this approval given based on a safety report that is not even “cooked” half way? After all, there is no emergency situation for children.
* Why did the FDA not address these manipulations and violations of the protocol after the company submitted its review?
Yaffa Shir-Raz, PhD, is a risk-communication researcher and a teaching fellow in the Interdisciplinary Center Herzliya in Israel, and the University of Haifa.
2. Pfizer. (2021). A PHASE 1/2/3, PLACEBO-CONTROLLED, RANDOMIZED, OBSERVER-BLIND, DOSE-FINDING STUDY TO EVALUATE THE SAFETY, TOLERABILITY, IMMUNOGENICITY, AND EFFICACY OF SARS-COV-2 RNA VACCINE CANDIDATES AGAINST COVID-19 IN HEALTHY INDIVIDUALS