Overview

Placebo Vaccines
Criteria J&J J&J Moderna Pfizer
Benefits (Efficacy)
varying benefit depending on subgroup
baseline
in (mild) COVID-19* AND testing too subjective and inaccurate*****
baseline (only below 60y)
benefit not proven
in severe COVID-19** >99.63% effective >99.91%
baseline benefit not proven
in severe COVID-19** Requiring Medical Intervention (MRU) >99.97% effective >99.97% effective
in duration of protection baseline benefit not proven
in populations at higher risk of severe COVID-19 baseline benefit not proven
in individuals previously infected with SARS-CoV-2 baseline benefit not proven
in pediatric populations baseline benefit not proven below 18
with changes in the virus, and/or potential effects of co-infections benefit not proven
against asymptomatic infection benefit not proven
against long-term effects of COVID-19 disease baseline benefit not proven
baseline benefit not proven
against mortality >99.97% effective >99.98% effective
against transmission of SARS-CoV-2 baseline benefit not proven
Useful efficacy**** baseline benefit not proven

Risks LOW*** HIGH unknown

local and systemic adverse reactions (very short term) Baseline increased (incomplete)
serious adverse events (short term) LOW but cohort not complete enough
safety in certain subpopulations (pediatric, elderly …) safety not proven
medium term (serious) adverse reactions None safety not proven
long term (serious) adverse reactions None safety not proven
vaccine-enhanced disease (VAED, VAERD, ADE …) None Yes: safety not proven
Experimental mRNA, DNA, genetically modified virus, nanopraticle None Yes: safety not proven
Virus threat enhancement through increased evolutionary pressure Baseline Unknown risk but potential impact is HUGE

Logistics, storage and administration None moderate very negative very negative

depends on unknown - unknown - very unknown - very

Benefits-risks balance individual negative negative negative

*at least 28 days after vaccination

**at least 28 days after vaccination and centrally confirmed cases
*** based on current mortality rate and depending on individual
**** efficacy in subgroups at risk of hospitalisation, severe morbidity, serious long-term effects and death
***** see the issues with non-severe covid-19

This paper provides a critical analysis of the Janssen Ad26.COV2.S Vaccine for the Prevention of COVID-19, based on the
FDA Briefing Document.

Above you can see a summary of the results, comparing them with other covid-19 vaccines and placebo.

On the next pages this is further explained and the underlying evidence is given.
Table of contents

Overview ................................................................................................................................................................................. 1
Introduction ............................................................................................................................................................................ 3
Trial Design Issues ................................................................................................................................................................... 4
Identification of cases in the trial and data quality ............................................................................................................ 4
Not fully double-blinded ..................................................................................................................................................... 5
Exclusions of positive SARS-CoV-2 ...................................................................................................................................... 6
Limited follow-up and safety testing .................................................................................................................................. 6
Vaccine Efficacy issues ............................................................................................................................................................ 7
Limitations in subgroups ..................................................................................................................................................... 7
Vaccine efficacy in important subgroups ............................................................................................................................ 7
Vaccine efficacy in severe and critical covid-19 ................................................................................................................ 10
Vaccine efficacy in mortality reduction ............................................................................................................................ 11
Trend in placebo deaths........................................................................................................................................................ 12
Disclosure statement ............................................................................................................................................................ 12
Conclusions ........................................................................................................................................................................... 13
Appendix 1 ............................................................................................................................................................................ 14
Johnson & Johnson (Janssen Ad26.COV2.S Vaccine) SARS-COV-2 vaccine: A Critical
Analysis of the Scientific Data

The first page gives a summary of the benefits and risks.

Introduction
We have made it clear on many occasions that we are NOT anti-vaxxers. In fact we are very much in favor of vaccination.
But it depends on the actual case. Any medical intervention must always respect the following:

● Primum non nocere (First, do no harm)

● Ensure that the intervention has a positive benefits-risks balance, for the individual and society, short-term as well
as long(er) term
● The intervention must be sustainable, durable and cost effective
● Public health and cost efficiency must be held as higher goals than commercial profits

In addition, the objectives must be taken into account and must be realistically possible. These could theoretically be (not
exhaustive):

1. Reaching “zero covid”, where active covid-19 and the underlying SARS-COV-2 is eradicated in human populations.
2. Eradication of viral reservoirs in humans (i.e. hiding latently in organs, bone marrow etc.) – if relevant.
3. Eradication of viral reservoirs in animals that could re-infect humans with new strains.
4. Creating herd-immunity to control the virus transmission and reduce transmission and infection rate to a
minimum.
5. Protecting the most vulnerable from severe / lethal disease.
6. Prevent or lower transmission.
7. Reducing the risk of new more virulent and/or infective SARS-COV-2 strains develop.
8. Prophylaxis to prevent people at risk from being infected.
9. Early outpatient treatment reducing the chance of worsening disease.
10. Early inpatient treatment that decreases the chance of developing a very severe / lethal disease.
11. Late stage ICU treatment to reduce high morbidity and mortality.
12. Continuous treatment to reduce the incidence “long haulers” syndrome.
13. Strategies to improve natural immunity and general health (e.g. underlying causes of severe covid-19).

Obviously, depending on the actual objectives, the weight of particular benefits or risks can be lower or higher.

The feasibility of the objectives is not discussed here. Neither will we discuss the different benefits and risks elements that
are highly connected to the objectives.

However, it has not been proven that (mass-) vaccination is attainable and can be effective to reach “zero covid” or even
sustainable herd-immunity with such a highly mutable virus, with “reservoirs” in animals, as well as potentially in humans
and their organs. It seems very unlikely, also considering how it has spread around the entire world. In any case, certain
populations will have to be excluded from vaccination, due to health conditions or other factors such as age.

In fact, the very experienced virologist and developer of vaccines, Geert Vanden Bossche, DVM, PhD virology, has given
a very dire warning of how mass-vaccination creates a much greater disaster through the immense evolutionary pressure
on the virus. (https://covexit.com/expert-sounds-the-alarm-about-risks-of-mass-vaccination/ ) This is outside of the
scope of this paper, but please read his warning. Be mindful of this possibility and its potentially tremendous impact on
public health when reviewing the results below.

For our other sources, please see the annexes.

Trial Design Issues

Identification of cases in the trial and data quality

1. The prescribed test method was not fully held to study protocol:

The need for a central laboratory test was described to confirm SARS-CoV-2 infection. However much of the data
included in this report was NOT centrally confirmed.

Due to the clear violation of this design protocol and the uncertainty of the reliability of unconfirmed data, we will only
include data that was centrally confirmed, unless further indicated. Please be aware of this important restriction when
reviewing other data from this trial.

For example, quote “Of 682 primary endpoint cases with positive PCR from any lab accrued at the time of the data
cutoff date, [only] 464 were centrally confirmed”.

And quote “for the subgroup analyses, cases with any positive PCR, including those still awaiting confirmation by the
central laboratory, were included”.

This also adds a degree of uncertainty to the quality of the data in the subgroup analyses, which is actually the most
important to prove the efficacy across all subgroups.

2. The test method is questionable for non-severe covid-19:

The centrally confirmed test is described by the manufacturer as “The Abbott RealTime SARS-C0V-2 assay is an Emergency
Use Authorization (EUA) test authorized by the U.S. FDA for use by authorized laboratories, using real-time (RT)
polymerase chain reaction (PCR) technology for the qualitative detection of nucleic acids from the SARS-CoV-2 virus and
diagnosis of SARS-CoV-2 virus infection from individuals meeting CDC clinical and/or epidemiological testing criteria”.

The test itself is thus not fully approved1 and there is not sufficient proof that it is relevant for non-severe covid-19. There
are some studies but they are very limited in scope and size.

In fact, the WHO has given clear guidance2 on the use of PCR testing. This is in contradiction with the former FDA’s EUA
for this test, which was only giving a “prediction” on the suitability of this test. (quote: “Overall, the results of this analysis
predict no significant cross-reactivity or microbial interference”).

1
https://www.fda.gov/media/136258/download (Abbott RealTime SARS-CoV-2: For use under an Emergency Use Authorization
(EUA) Only)
2
https://www.who.int/news/item/20-01-2021-who-information-notice-for-ivd-users-2020-05 (Nucleic acid testing (NAT)
technologies that use polymerase chain reaction (PCR) for detection of SARS-CoV-2)
According to the WHO, for deciding on a positive test the disease prevalence must be taken into account (aka Bayes’
Theorem) where prevalence may be low and where enough other factors (e.g. in severe disease) are present. We analyze
from this report the actual disease prevalence for the correction of any individual test was NOT taken into account.

In contrast, the manufacturer still refers (at this time of writing) to outdated WHO guidance3 : 2nd March 2020

3. The initiation of the testing was purely based on an “unscheduled illness visit” adding another degree of
subjectivity to the non-severe covid-19 tests and cases.
4. The definition of (non-severe) covid-19 cases is problematic

This means that for example, anyone with a positive RT-PCR (with its known limitations and misuse, see previous points),
plus a headache and muscle pain, is counted as a positive case. This is arbitrary and not specific enough. The grade of
such symptoms is also relative and subjective. For example, another participant (e.g. in the vaccinated group), may very
well consider some headache and muscle pain as a sign of something else and not initiate a RT-PCR test.

Furthermore a far more specific case (e.g. with radiologic evidence) is equated to a less specific one. It’s really like
comparing apples and oranges.

Not fully double-blinded

5. The briefing document reveals that blinding was not strictly followed in the study:
● Part of the cohorts where prematurely un-blinded: 1046 (5.3%) and 1138 (5.8%).
● A greater proportion of participants ≥60 years of age were un-blinded (6.6%) compared to those 18 to
59 years of age (4.4%).
● The vast majority (93.0%) of participants who were un-blinded were from US study sites. These
participants were included in the per-protocol set until the time of the un-blinding.

The lack of blinding adds a degree of subjectivity in such endpoints where it matters (mild-moderate covid-19) in
particular because it was mostly in a subgroup that is more at risk of “real” covid-19.

3
https://apps.who.int/iris/handle/10665/331329 (Laboratory testing for coronavirus disease 2019 (COVID-19) in suspected human
cases: interim guidance, 2 March 2020)
Exclusions of positive SARS-CoV-2
6. Of the participants, those 4399 (10.0%) with positive SARS-CoV-2 status at time of vaccination based on serology
and/or PCR were excluded.

The intervention is therefore designed for people who are not SARS-CoV-2 positive. It means that when used in the
general population, it should actually also be verified before vaccination that the subject is not positive.

On the other hand, this important group which is excluded, hasn’t been tested (well) in this trial and cannot be
excluded that the vaccine will be administered to subjects that were not sufficiently part of the test group.

Limited follow-up and safety testing

7. Of the randomized participants (44325), the number of participants vaccinated was 21895. But only 21491
(54.7%) of the total remaining participants (vaccinated and placebo) had at least 8 weeks follow-up:
● The safety subset was further limited to 3356 (15.3%) and 3380 (15.4%) .
● Fewer participants in the safety subset compared to the FAS were seropositive at baseline (4.5% versus
9.6%) and had a least one comorbidity (34.1% versus 40.8%).
● The safety subset included only a very limited number of people aged ≥75 : 150 (4.5%) and 138 (4.1%).
● Geographically, the safety subset was limited to participants in the United States (51.4%), South Africa
(10.2%), and Brazil (38.5%).
● The safety subset for different ethnicities, e.g. Asians, with only 114 (3.4%) and 105 (3.1%) was very
small.

The further limitations (in numbers) and bias raise questions about the safety of the intervention, in particular in people
with comorbidities and aged ≥75, or different ethnicities, which are among the subgroups with the highest risks of
(Severe) Adverse Events (SAEs) and who are often targeted with priority in vaccination strategies.

.
Vaccine Efficacy issues
Limitations in subgroups
8. For the determination of vaccine efficacy, there were a priori limitations in the cohorts’ compositions with clear
consequences for the relevance of the results, including:
● The number of elderly included was very low at ≥75 with only 755 (3.8%) and 693 (3.5%) participants.
● The largest part had no comorbidity, at 11800 (60.1%) and 11824 (60.0%) while covid-19 is
predominantly critical in this subgroup4 .

Vaccine efficacy in important subgroups

9. According to the results (see below), people aged 60 years and above, over (a short) time, the generalized efficacy
drops about 10% (from 76.3% to 66.2%) when measured with an onset after 28 days instead of 14 days. In this
important subgroup (60 years and above), the efficacy can be as low as 36.7%

The drop in efficacy is contrary to what is expected of a vaccination where better immunity is supposed to be built up.
This suggests a lack of durability of vaccine efficacy.

This phenomenon can also be explained by statistical fluctuations. In this case it raises more questions about the overall
statistical foundation and relevance of this study.

10. In the age group 75 years and above, no statistically significant benefit was found from 28 days after
vaccination onwards. The vaccine was NOT proven to be effective for that age group.

Note that this suggests the vaccine may not have overall efficacy for people aged 75 years and above Note that this
“bad result” even includes non-centrally confirmed cases and the data quality is suspect. Note that even the age group
65 years and above may have low overall efficacy at only 38.6%

4
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2777028 (Outcomes and Mortality Among Adults Hospitalized
With COVID-19 at US Medical Centers)
 11. In the same non-centrally identified results, the overall efficacy in females is significantly lower than in males
and can be as low as 46%

The actual female “cases” are also higher. This raises questions about the overall study quality and the population
composition. This finding is contrary to the general global findings where severe/lethal covid-19 trends to be more of a
male problem.

12. In the same non-centrally verified results, the overall efficacy in ethnic subgroups is not statistically significant.

13. In the same non-centrally verified results, the overall efficacy in age group 60 years and above and with
comorbidity, is not statistically significant.
14. In the same non-centrally verified results, the overall efficacy in particular comorbidities, is not statistically
significant.

15. In the same non-centrally verified results, the overall efficacy in the important type 2 diabetes mellitus
comorbidity, is not statistically significant and shows a trend of very low efficacy.
Vaccine efficacy in severe and critical covid-19

16. The overall efficacy in severe covid-19, is not statistically significant in the most important age group of 60 years
and above:

17. The overall efficacy in severe covid-19 requiring medical intervention, is not statistically significant:
Vaccine efficacy in mortality reduction

18. There was no statistically significant proof that vaccination has overall efficacy in mortality reduction related to
covid-19.

The (7) deaths recorded (in the placebo group) are not certain to be related to covid-19 : quote “not all have been
centrally confirmed to date”. It is also reported that “all 7 deaths occurred in the placebo group and were in study sites
in South Africa.”

This raises questions about the true cause of these deaths and the quality of the data.

In an update paragraph it was later claimed that 6 deaths were attributed to covid-19. Since one of these cases was SARS-
CoV-2 PCR positive at baseline, that case has to be excluded to be in line with the policy of the vaccinated group (see
previous points).

This means that of all the participants in the placebo group and with the same presumption of risk, maximum 5 covid-19
related deaths occurred. Given the nature of the comorbidities (see next section) this could be less.

Even with 5 deaths, the risk of dying of covid-19 in the placebo groups was:

5/19544
This means the placebo seems to protect against mortality with an efficacy of >99.97%.

In other words, in this study in the placebo / control population, the risk of dying from covid-19 was probably less than
0.03%.

In contrast the deaths in the vaccinated group reveals the following:

Quote: “Two deaths in the vaccine group were secondary to respiratory infections not due to COVID-19. A 61-year-old
participant died of pneumonia on Day 24 following onset of symptoms on Day 13. A 42-year-old participant with HIV died
on Day 59 following diagnosis of a lung abscess on Day 33. A 66-year-old participant died of unknown causes after waking
up with shortness of breath on Day 45.”

None of these deaths is attributed to covid-19 even though many deaths seem to be respiratory infections. Nowadays
these deaths are classified as covid-19, and shortness of breath is described in the case definition of a typical covid-19
sign.

It is not clarified if these cases were verified with a central test and if (in case a negative PCR test was demonstrated locally
or centrally) it could have been “false negatives”.

From this data we have to conclude that there could have been 3 deaths related to covid-19 in the vaccinated group,
leading to a similar efficacy. The Absolute Risk Reduction (ARR) (if the result was statistically significant, which is not the
case even) was then 0.009%

In the very best case (7 placebo and 0 vaccinated covid-19 deaths), the ARR would still only be 0.03%

In any case the number of cases are too small either way to prove efficacy.
Trend in placebo deaths

The few placebo deaths observed in this large study, show a remarkable trend. Almost all had one or more comorbidities,
and in particular, almost for all, obesity was a common factor. Also hypertension and diabetes were common underlying
causes.

Disclosure statement

The FDA Briefing Document, even though composed by the FDA, appears to have been made with information provided
entirely by the sponsor (Janssen Biotech, Inc.)

From this we can conclude that there is a potential conflict of interest to be declared. This may raise doubt about the
results that have been discussed in this analysis.
Conclusions

The above analysis shows most of the evidence for the summarized conclusion on benefits and risks in the
overview.

The useful efficacy has not been proven for this medical intervention.
The benefits are uncertain. In addition, there are many risks that are still unknown
unclear and difficult to conclude at
Based on these results it’s this stage that an objective
evaluation on a positive benefits / risks balance can be made.
From this perspective, it would be unwise to grant an EUA. In particular in relation to the overall concern
about a mass vaccination strategy to deal with covid-19.
Though, please note, that absence of proof does not prove absence (of sufficient benefits over risks)
In addition, this does not mean that this vaccine seems less suitable than the EUA’s already given for other vaccines. In
fact it seems that this
vaccine shows slightly more (“gold standard”) evidence of potential useful
efficacy compared with the other vaccines that were given EUA. In addition it holds additional advantages in
logistics, storage and administration. Though in contrast, the technology is even more experimental
and may hold additional risks in this area.
Given the uncertainties, the administration of this vaccine should be based on personal risk-based assessment.

This should take into account the limitations in this study in terms of appropriateness e.g. age below 60, age above

18, ethnicity and negative covid-19 status. The last condition implies that anyone receiving the vaccine should
have been tested for covid-19 not long before the vaccination.

However, we do want to point at the need for very clear informed consent.
objectivity, impartiality, unprejudiced and unbiased fairness,
We also want to call for
when evaluating other possible medical interventions to mitigate risks of covid-19, and to do
this consistently.
Appendix 1

The source of this report is the “FDA Briefing Document Janssen Ad26.COV2.S Vaccine for the Prevention of COVID-
19”.

To review this yourself, you can go straight to the sections “8.1 Known Benefits”, “8.2 Unknown Benefits/Data Gaps”, …
“8.4 Unknown Risks/Data Gaps” or, much better, check the study design and the actual results and statistics.

The comparison with the other vaccines is based on the FDA Briefing Documents for EUA. (please see the FDA website)