3T Study journal club critical appraisal

1.  Study Snap: Title, Journal, Date

2.  Background: LitRev, Gap, PICO’Q
o Data exists that SARS-COV-2 vaccines efficacy mostly wanes
over time as suggested by declining antibodies titers and real
life symptomatic (but not much severe/fatal) COVID-19 events.
o Pfizer announced the first RCT of its BNT162b2 booster against
Placebo showing extra 95.6% protection against COVID-19 in
o FDA firstly approved the BNT162b2 booster dose in 09/2021
based on the submitted prelim data of the above.
o Concerns were raised regarding the target population and the
equity of vaccine distribution.

3.  Background: LitRev, Gap, PICO’Q
o Israel was one of the first countries to apply mass SARS-COV-2
immunizations and has a high rate of full vaccinations.
o Israel in 07/2021 made the BNT162b2 booster indicated, first
for 60yo then 50yo, who had received 2 doses at least 5m prior.
o The Clalit Health Services (CHS) is the largest of 4 health care
systems in Israel covering 52% of the population, and has its
own large database.
o A separate trial using the same database was conducted on
those above 60yo around the same time.

4.  Inclusion Criteria:
o Adults of 50 years of age and above
o Received 2 doses of BNT162b2 at least 5 months prior

5.  Exclusion Criteria:
o Missing data regarding Date of Birth or Sex
o Received the booster before the study start time
o COVID-19 infection previously OR within 3 days of the
effective booster date (defined as 7 days from delivery).

6.  Methods: Type, Place/Time, Fund
o Type: Prospective Interventional
o Place: Israel
o Time:
o Approval: CHS Community Helsinki Committee and Data
Utilization Committee.

7.  Methods: Flowsheet, Dur, Losts
o Intervention: BNT162b2 booster given to the eligible population
o Extraction: CHS Electronic Medical Records, including
- Personal & Medical data - COVID daily database

8.  Methods: Flowsheet, Dur, Losts

9.  Methods: Flowsheet, Dur, Losts
85,090 (10%)
758,118 (90%)

10.  Demographics & Characteristics:

11.  Statistical Analysis: Used Ways
o Primary Endpoint: Death due to COVID-19
o Secondary Endpoints: SARS-COV-2 infection by RT-PCR
o 7-Day assumption confirmation: Estimating HR of Death up to 7d
o Used Tests: - Chi Square - Kaplan-Meier Analysis - Cox Regression
o Software: - R statistical software, v 3.5.0 - SPSS, v 26

12.  Outcomes: 1ry & 2ry & Safety,S/E
2.98/100,000
0.16/100,000

13.  Outcomes: 1ry & 2ry & Safety,S/E

14.  Outcomes: 1ry & 2ry & Safety,S/E

15.  Outcomes: 1ry & 2ry & Safety,S/E

16.  Outcomes: 1ry & 2ry & Safety,S/E
(P<0.001)

17.  Conclusion: Theirs, Yours, Applic
o BNT162b2 booster shot given at least 5 months after the second
dose, reduced mortality due to COVID-19 by 90% compared to
those who did not receive the booster, and also reduced the risk
of SARS-COV-2 infection.

18.  Limitations: Bias, Cheat, Appraise
o Short study period of 54 days
o Patients >60yo received the booster earlier than those <60yo
o Lack of data regarding adverse events
o B.1.1529 (Omicron) variant of SARS-COV-2 was discovered in 11/2021 after
the trial, with early data suggesting high transmissibility and raising the
need for further boosters data.