Cardiovascular Signal in mRNA vaccine Clinical Trials

Review of paper by C. Michels et al "Forensic analysis of the 38 subject deaths in the 6-Month Interim Report of the Pfizer/BioNTech BNT162b2 mRNA Vaccine Clinical Trial", 10/2023

Review Date: November - 2023

Overview:

We review the paper, by Michels et. al. published on 10/2023 in the International Journal of Vaccine Theory, Practice, and Research, that provides a forensic analysis of the BNT162b2 mRNA clinical trials and the timeline of released documents and up to the 6 month mark (after the unblinding), in March 2021. The paper reference is:
C. Michels et al, "Forensic analysis of the 38 subject deaths in the 6-Month Interim Report of the Pfizer/BioNTech BNT162b2 mRNA Vaccine Clinical Trial". (2023). International Journal of Vaccine Theory, Practice, and Research , 3(1), 973-1008. Link: https://doi.org/10.56098/ijvtpr.v3i1.85

The excess mortality rate for cardiovascular diseases were already associated to the Covid-19 vaccinations as there was already a clear signal during the Pfizer clinical trials. In their recent paper Michels et. al., provide a forensic analysis of the BNT162b2 mRNA clinical trials, showing that in the clinical trials, after 6-months, 12 subjects died of a cardiac event, 9 of whom were vaccinated and 3 unvaccinated.
Our review of the paper is significant in the context of our work on the analysis of cause of death, as it establishes a direct link between our analysis of deaths due to cardiovascular events in the UK, that uses data from the UK Office for National Statistics (ONS) and the original phase III clinical trials for the Covid-19 mRNA vaccines.

Summary of the results:

Higher all cause mortality in the vaccine arm.
• The authors find that the Pfizer/BioNTech BNT162b2 vaccine was associated with higher all cause mortality.
  Of the 38 deaths reported in the 6-Month Interim Report of Adverse Events, 21 BNT162b2 vaccinated subjects died compared to 17 placebo subjects.

Delayed reporting of deaths at the EUA (Emergency Use Authorisation) point.
• Delayed reporting of the subject deaths into the Case Report Form, which was in violation of the trial protocol, allowed the EUA to proceed unchallenged.

Cardiac signal.
• The was a 3.7-fold increase in cardiac events in subjects who received the BNT162b2 vaccine versus the placebo.
  Of the 15 subjects who were Sudden Adult Deaths (SAD) or Found Dead (FD), 12 died of a cardiac event, 9 of whom were vaccinated.
  The cardiac event signal was obscured by delays in reporting the accurate date of subject death that was known to Pfizer/BioNTech in the subject's Narrative Report.

Review of the paper:

The Pfizer and Moderna trials were expected to follow the participants for two years. However, within weeks of the emergency authorisation, the sponsors began a process of elective unblinding of participants, and those who had received the placebo were offered the vaccine. The unblinding compromised the post-authorisation data.
On November 20, 2020 Pfizer/BioNTech submitted to the US FDA an Application for Emergency Use Authorization (EUA) for an Unapproved Product Review Memorandum. The Application described the clinical trial results to the data cut-off of November 14, 2020. The FDA made a copy of the EUA Application available on their website on December 11, 2020. This was the first opportunity for the public and medical professionals to evaluate the clinical trial data reportedly supporting the safety and efficacy of their BNT162b2 mRNA vaccine.
Polack et al.(2020) published a journal article on December 10, 2020, entitled, “Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine”. The authors of Polack et al. consisted of the site administrators of the 153 clinical trial sites in over 6 different countries. Fernando P. Polack, MD, was Principal Investigator and site administrator of the trial site in Argentina and Stephen J. Thomas, MD, the lead co-author, was the chief Principal Investigator of Clinical Trial C4591001. Thus, the authors of these publications were obliged to be and should have been intimately familiar with the trial findings. On September 15, 2021, the same group of site administrators published another journal article entitled: “Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine through 6 months” (Thomas et al., 2021).
Additionally, the detailed data of the clinical trials were not to be made available for analysis by independent researchers for 75 years.
Public Health and Medical Professionals for Transparency (PHMPT), a non-profit alliance of over 80 public health officers and medical researchers, filled a FOIA lawsuit in the US District Court, Fort Worth, Texas in September 2021 to obtainand disseminate the original clinical trial data upon which the FDA relied when it licensed Pfizer’s (Comirnaty) COVID-19 mRNA vaccine.
The PHMPT case was approved. Over the objections of the FDA, a Federal Court Judge ordered the expedited release of Pfizer’s clinical trial data and documents at the rate of 55,000 per month. Data release began early in June 2022 to the Public Health and Medical Professionals for Transparency Documents site and was projected to take 8 months to complete. Unfortunately, it is taking much longer than estimated and documents continue to be downloaded to this site. The overwhelming size and complexity of these documents stimulated the formation of the DailyClout Pfizer/BioNTech Document analysis volunteers, a group of medical professionals, scientists, data analysts, statisticians, lawyers, and more, who have offered up their time and skills to analyze the Pfizer/BioNTech clinical trial documents. Team 3 is a subset of these volunteers dedicated to data investigation.

Methods (Material used in the independent analysis of the clinical trials):
The original Pfizer/BioNTech documents are available at Public Health and Medical Professionals for Transparency (PHMPT) website (https://phmpt.org/pfizers-documents/). The following documents were downloaded from this site and were the main sources of data for our analysis:

• 6-Month Interim Report (16.2.7.4.1 Listing of Adverse Events –All Subjects ≥16 Years of Age) (6-Month Interim Report of Adverse Events C4591001)
• Randomization Scheme and Actual Vaccine Received (16.1.7.1 Listing of Randomization Scheme and Actual Vaccine Received –All Subjects ≥16 Years of Age) (Listing of Randomization Scheme and Actual Vaccine Received)
• Listing of Discontinued Subjects (16.2.1.1 Listing of Subjects Discontinued From Vaccination and/or From the Study –All Subjects ≥16 Years of Age) (Listing of Discontinued Subjects)
• 6-Month Summary of Clinical Safety (2.7.4 Summary of Clinical Safety) (Summary Clinical Safety 6-Month Report)
• Narrative Reports on Subject Deaths from 6-Month Interim Report (125742_S1_M5_5351_c4591001-interim-mth6-narrative-sensitive)

Additional information came from the following:
• Pfizer/BioNTech Clinical Trial C4591001 –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 (https://classic.clinicaltrials.gov/ct2/show/NCT04368728)
• Emergency Use Authorization (EUA) for an Unapproved Product (Emergency Use Authorization for an Unapproved Product Review Memorandum Https://Archive.Org/Details/Emergency-Use-Authorization-Eua-for-an-Unapproved-Product-Review-Memorandum)
• Analysis Data Reviewer Guide –BLA Analysis for Participants ≥16 Years of Age, BioNTech SE and PFIZER INC, Study C4591001 (Analysis Data Reviewer Guide BLA Analysis for Participants ≥16 Years of Age BioNTech SE and PFIZER INC. Study C4591001 Https://Phmpt.Org/Wp-Content/Uploads/2022/03/125742_S1_M5_c4591001-A-Adrg.Pdf#page=85)

Results:
The table below, copied from the table 1 of the paper, summarises the deaths during, the Pfizer clinical trials up to the 6 month point (from July 27th 2020 to March 13th 2021).

Diagnosed Cause of death of Pfizer/BioNTech Clinical Trial Subjects. Table 1 of paper.

#	Sex	Age	Date of Death	Days post dose 1	Primary Cause of Death (Secondary cause)
BNT162b2 mRNA vaccinated subjects (21 deaths)
1	M	60	13/Sep/2020	4	Arteriosclerosis
2	F	64	19/Oct/2020	63	Sudden cardiac death
3	F	56	21/Oct/2020	84	Cardiac arrest
4	F	58	07/Nov/2020	96	Cardiac arrest
5	M	72	11/Nov/2020	36	Shigella Sepsis
6	F	63	12/Nov/2020	99	Chronic obstructive pulmonary disease
7	M	85	18/Nov/2020	90	Arteriosclerosis (Hypertensive heart disease)
8	M	53	04/Dec/2020	107	Cardio-respiratory arrest
9	M	76	19/Dec/2020	52	Cardiac arrest
10	M	54	19/Dec/2020	111	Cardiac failure - congestive
11	F	87	21/Dec/2020	120	Septic shock
12	F	62	24/Dec/2020	95	Road traffic accident
13	M	81	26/Dec/2020	132	Covid-19 pneumonia
14	M	59	29/Dec/2020	137	Cardiac arrest
15	M	77	12/Jan/2021	144	Sepsis (Emphysematous cholecystitis)
16	M	51	19/Jan/2021	132	Lung cancer metastatic
17	M	67	29/Jan/2021	178 (5)	Suicide
18	F	79	03/Feb/2021	149	Myocardial infarction
19	M	64	10/Feb/2021	112	Road traffic accident
20	M	84	15/Feb/2021	147 (26)	Cardio-pulmonary arrest (Cerebrovascular accident)
21	M	83	06/Mar/2021	186	Metastases to lung (Pancreatic carcinoma metastatic)
Placebo subjects (17 deaths)
1	F	42	26/Aug/2020	8	Death (Undetermined)
2	F	61	28/Sep/2020	35	Haemorrhagic stroke
3	M	53	02/Nov/2020	54	Overdose
4	M	58	03/Nov/2020	16	Myocardial infarction
5	F	51	04/Nov/2020	56	Myocardial infarction
6	M	65	18/Nov/2020	86	Aortic rupture
7	M	66	28/Nov/2020	121	Pneumonia
8	M	66	01/Dec/2020	93	Cardiac arrest
9	M	47	06/Dec/2020	101	Cardio-respiratory arrest
10	M	67	17/Dec/2020	108	Metastases to liver (Biliary cancer metastatic)
11	F	57	18/Dec/2020	102	Acute respiratory failure (Covid-19 pneumonia)
12	F	82	30/Dec/2020	146	Dementia
13	F	56	05/Jan/2020	97	Diabetes mellitus (Covid-19 pneumonia)
14	M	65	11/Jan/2020	104	Multi-organ dysfunction syndrome (Covid-19)
15	F	59	31/Jan/2020	156	Multi-organ dysfunction syndrome (Covid-19)
16	M	65	09/Feb/2020	97	Bacterial pneumonia
17	F	68	13/Feb/2020	156	Respiratory failure (Covid-19)

Conclusions of the paper:
1 - The C4591001 placebo-controlled randomized clinical trial of 22,030 vaccinated and 22,030 placebo subjects was the world’s only opportunity for an unbiased evaluation of the Pfizer/BioNTech BNT162b2 vaccine.
2 - Unblinding of placebo subjects starting in Week 20 terminated the placebo-controlled clinical trial, thereby ending all unbiased evaluation of possible adverse event signals.
3 - The mRNA-LNP platform is novel, not previously phase 2/3 tested in humans, and the toxicity of PP-Spike protein was unknown. Taken together, a 20-weeks placebo-controlled clinical trial is NOT sufficient to identify any except for the most common safety concerns.
4 - The number of all-cause deaths is NOT decreased by BNT162b2 vaccination.
5 - Of the 38 deaths reported in the 6-Month Interim Report of Adverse Events, 21 BNT162b2 vaccinated subjects died compared to 17 placebo subjects.
6 - Delayed reporting of the subject deaths into the Case Report Form, which was in violation of the trial protocol, allowed the EUA to proceed unchallenged.
7 - The number of subject deaths was 17% of the expected number, based on age-adjusted US mortality. One possible explanation could lie in the 395 subjects that were “Lost to Follow-up”.
8 - There was a 3.7-fold increase in cardiac events in subjects who received the BNT162b2 vaccine versus the placebo.
9 - Of the 15 subjects who were Sudden Adult Deaths (SAD) or Found Dead (FD), 12 died of a cardiac event, 9 of whom were vaccinated.
10 - The cardiac adverse event signal was obscured by delays in reporting the accurate date of subject death that was known to Pfizer/BioNTech in the subject’s Narrative Report.

Note:
In the sections above we limited ourselves to mostly transcribe the results and the main explanations from the original paper. These results are not exhaustive and the authors of the paper produce many more interesting findings that are worth reading. Next we will provide some of our own insights into the forensic analysis of the Pfizer/BioNTech clinical trial.

Observations

In this section we provide some observations and thoughts related to the paper that was reviewed above. These observations are of revelance in the context of many of our ongoing research projects that investigate excess mortality during the pandemic years. Many of the patterns and findings in our different research projects are related to the Covid-19 disease, the pandemic lockdowns and other measures introduced by health authorities worldwide and from 2021 the population-wide vaccination campaign based on a novel gene based technology based on mRNA, for which the clinical trials were cut short.
The paper reviewed above is the highest quality available data on possible adverse events (deaths) related to these novel inoculations. Even though, in our view, the clinical trials did not have a large enough sample, some of the following observations might correspond to actual signals, that need to be investigated at a population level.

• Covid-19 signal.
  We observe that there were 5 Covid-19-related deaths in the placebo group, while only 1 in the vaccine arm, pointing towards vaccine efficacy,
• Cardiac signal.
  Referring to the definitions from the authors of the paper, we observe that there were 9 cardiac-related deaths in the vaccine arm while only 3 in the placebo group.
  In our research, we find evidence of this possible signal in our research on cardiovascular deaths in the UK. The analysis of deaths in the whole cardiovascular system can be found here, and the analysis of individual cardiovascular causes, here.
• Early cancer signal?
  We observe that there were 2 deaths from metastatic cancer in the vaccine group while only 1 in the placebo group. Could this indicate an early signal that identifies accelerated outcomes for exisiting cancers or the new phenomenon of "turbo-cancers"?
  In our research, we find evidence of this possible signal in our research on malignant neoplasms deaths in the UK. The analysis of deaths for all malignant neoplasms can be found here, and the analysis of individual malignant neoplasm causes (including cancers without site specification), here.
• Road traffic accidents?
  We observe that there were 2 deaths from road traffic accidents in the vaccine group while none in the placebo group. Is this a signal or spurious event?
• Sepsis-related deaths?
  We observe that there were 3 sepsis-related deaths in the vaccine group while none in the placebo group. Is this a signal or spurious event?
• All-cause mortality signal?
  We observe that there were 21 deaths in the vaccine group while 17 in the placebo group, corresponding to excess deaths around 23%. Is this an early signal that corroborates the excess mortality we observe in the nations we've investigated? (link to our excess mortality analysis)