On 2021-08-02 22:47:42, user drwambier wrote:
Please revise: "No new serious adverse events assessed as related by investigators were reported after data cut-off for the previous report."
Previously reported: 2 deaths (BNT162b2) vs 4 (placebo), with zero deaths related to COVID19 in each arm. Death (any cause) is the main SERIOUS ADVERSE EVENT (SAE), and a higher number was reported, please revise accordingly.
"During the blinded, controlled period, 15 BNT162b2 and 14 placebo recipients died; during the open-label period, 3 BNT162b2 and 2 original placebo recipients who received BNT162b2 after unblinding died. None of these deaths were considered related to BNT162b2 by investigators. Causes of death were balanced between BNT162b2 and placebo groups (Table S4).”
Since you are reporting the 6 months data, please consider rephrasing to the full numbers: "18 deaths on BNT162b2 versus 16 deaths on the placebo (including the 2 deaths after receiving BNT162b2)." It is also important to specify the denominator for each group. It is unclear what is the total number of patients were followed-up for full 6 months, and how many were lost to follow-up (survivor bias?).
"Cumulative safety follow-up was available up to 6 months post-dose 2 from combined blinded and open-label periods for 12,006 participants originally randomized to BNT162b2. The longer follow-up for this report, including open-label observation of original BNT162b2 recipients and placebo recipients who received BNT162b2 after unblinding, revealed no new safety signals relative to the previous report”.
If 3 deaths happened in the BNT162b2 group until 1 month after Dose 2 during the blinded period and 5 in the placebo group, the new deaths after that month were: 15 for BNT162b2 and 11 for placebo (including the 2 deaths after receiving BNT162b2). Please verify if this is correct, if it is, please state specifically as this might be considered a safety signal.
200 HIV patients data is still not disclosed. I understand that this is per protocol. However, we ask to please disclose the current HIV+ data, since many are receiving the shots under EUA without data of their subgroup analysis.
Plus, assuming that those are in the 22,166 patients of BNT162b2 and 22,320 of placebo:<br />
Considering the “scenario of all patients followed, without unknown outcomes”:<br />
RR for death is 1.1328 (.5778-2.2208). An increase by 13% of all cause mortality in 6 months of follow-up including the part of vaccinating the placebo arm.<br />
The ages and gender of deaths would be informative for safety since populations were balanced by randomization please add a table with such information.
Current data suggests that within 6 months of follow-up, BNT162b2 does not reduce all-cause mortality. There is a signal that it might increase all-cause mortality. <br />
Assuming that it would be difficult for investigators to access if deaths were related to BNT162b2 since myocarditis or heart-related side effects were initially thought to be unrelated to BNT162b2, also no previous signals of thrombosis were reported.
Causes of death were assumed to be “Cardiac Arrest” or other "unknown" descriptions. There is even a “death” as cause of death on the table… "dementia?" For future trials or third injection, an active screening for myocarditis (Serum Cardiac Troponin T and Creatine Kinase–MB), and thromboembolic events would be prudent, specially in the >65 y.o. population, which may be more vulnerable to momentary reduction of cardiac muscle function through inflammation.
As this was a healthy population (not treatment of COVID-19, etc), and deaths were rare. <br />
It seems that all-cause mortality was indeed more common than deaths by COVID-19 in the current manuscript, thus, they cannot be left aside from the trial results discussion. Please discuss specifically about the comparison of COVID-19 deaths in the control group vs the relative increase of deaths detected in the BNT162b2 group and how putting those numbers in the balance.
About COVID-19 related deaths, the score was expected: 2 deaths on placebo (“COVID-19”) and 1 death in Vaccine ("COVID-19 pneumonia”). <br />
With the current safety data, caution is warranted, since the number to harm in the best scenario points that approximately 100 deaths could be attributed to the vaccine for every 1M fully vaccinated, if the increase in all-cause deaths is not a noise of low numbers.
"Safety monitoring will continue per protocol for 2 years post-dose 2 for participants who originally received BNT162b2 and for 18 months after the second BNT162b2 dose for placebo recipients who received BNT162b2 after unblinding.”
Was all the control group crossed-over to BNT162b2 post-unblinding? If so, please state and give the reasons why it was decided to do so. If there is no placebo arm for a safety control comparison, this safety monitoring will only be important if extreme flags happen: such as unexpected high number of serious adverse events emerge.