Open Letter to Regulatory Authority Assessors for COVID-19 Vaccine

In light of their momentus task of being asked to impartially review an application for a COVID-19 vaccine, which is being hailed as a saviour to our planet, I have produced this open letter to the regulatory assessors from the US FDA, the European Medicines Agency and the UK MHRA.

The letter contains not only my concerns of the pressures being applied to the regulators, who are expected to remain impartial, but also includes relevant information regarding the clinical landscape and the findings of a recent EU Member State Court of Appeal decision that determined the RT-PCR test as being not fit-for-purpose as a diagnostic tool for COVID-19.
 

US Food and Drug Administration
European Medicines Agency
Medicines and Healthcare products Regulatory Agency
 

23 November 2020

 

Dear Assessors and (Co)Rapporteurs for COVID-19 Vaccine(s)

 

Both a great responsibility and burden has been placed upon you in relation to the assessment of Pfizer’s COVID-19 vaccine licence application and in the future for those from Moderna, AstraZeneca and undoubtedly others.

Following the recent vaccine trial interim analyses announcements by CEOs, and the resulting speeches by political leaders around the globe, I was both shocked and appalled by the pressure they have now heaped on you as regulators.

Interim analyses are at best a good indication of what the final data set may hold, and in my opinion, they should never be used as a financial or political tool, particularly when it puts added pressure on independent regulators such as yourselves.

I do not for one moment envy the position you now find yourselves in, for what has undoubtedly become the most important regulatory review of your lives. I trust however that due to your loyalty to the patients you represent, and who’s safety you hold in your hands, you will act without prejudice.

I understand that during any assessment of an application you must closely scrutinise the presented data but also the clinical landscape for which the product, in this case a vaccine, is intended for.

I feel it is extremely important for you to take into consideration the following factors when reviewing any application for a COVID-19 vaccination product licence:

  1. In a recent Lisbon Court of Appeal case[1] from 11 November 2020, the Judges ruled as follows:

    “In view of the current scientific evidence, [the RT-PCR] test alone is incapable of establishing beyond reasonable doubt that such positivity in fact corresponds to a person's infection with the SARS-CoV-2 virus ...”

    A translated version[2] of the entire judgment includes reference to the Jafaar et al. 2020[3] study and directly quotes from the study that “at a cycle threshold (ct) of 25, about 70% of the samples remained positive in the cell culture (i.e. they were infected): in a ct of 30, 20% of the samples remained positive; in a ct of 35, 3% of the samples remained positive; and in a ct above 35, no sample remained positive (infectious) in the cell culture.
    This means that if a person has a positive PCR test at a cycle threshold of 35 or higher (as is the case in most US and European laboratories), the chances of a person being infected are less than 3%. The probability of a person receiving a false positive is 97% or higher.”

    Following their own interpretation the Judges conclude “the possible reliability of the PCR tests carried out depends from the outset on the threshold of amplification cycles they involve, so that up to a limit of 25 cycles, the reliability of the test will be around 70%; if 30 cycles are carried out, the degree of reliability falls to 20%; if 35 cycles are reached, the degree of reliability will be 3%.”

    The judgment goes further to discuss the Surkova et al. 2020[4] study, and the Judges highlight “the many questions raised by the accuracy of the test itself, regarding the specific detection of the SARS-CoV-2 virus, because of strong doubts regarding compliance with the so-called gold standard” and then apply this to the following direct text from the study itself:
    “Any diagnostic test result should be interpreted in the context of the pretest probability of disease. For COVID-19, the pretest probability assessment includes symptoms, previous medical history of COVID-19 or presence of antibodies, any potential exposure to COVID-19, and likelihood of an alternative diagnosis.
    When low pretest probability exists, positive results should be interpreted with caution and a second specimen tested for confirmation. Notably, current policies in the UK and globally do not include special provisions for those who test positive despite being asymptomatic and having laboratory confirmed COVID-19 in the past (by RT-PCR swab test or antibodies). Prolonged viral RNA shedding, which is known to last for weeks after recovery, can be a potential reason for positive swab tests in those previously exposed to SARS-CoV-2. However, importantly, no data suggests that detection of low levels of viral RNA by RT-PCR equates with infectivity unless infectious virus particles have been confirmed with laboratory culture-based methods.
    If viral load is low, it might need to be taken into account when assessing the validity of the result.
    To summarise, false-positive COVID-19 swab test results might be increasingly likely in the current epidemiological climate in the UK, with substantial consequences at the personal, health system, and societal levels.”

    The above was sufficient for the Judges to conclude “since there are so many scientific doubts, expressed by experts in the field, as to the reliability of [RT-PCR] tests, ignoring the parameters of their performance and having no diagnosis made by a physician as to the existence of infection and risk, it would never be possible for this court to determine that [the individual in question] was a carrier of the SARS-CoV-2 virus, nor that [the three other individuals] had high risk exposure” and the appeal was dismissed.

    In light of the aforementioned judgment and taking into consideration that the clinical trial protocols relied upon by the applicants, including but not limited to Pfizer, Moderna and AstraZeneca for their COVID-19 vaccines, using a positive RT-PCR test, whether in isolation or with a patient-described symptom, to determine a COVID-19 infection brings into serious doubt whether a COVID-19 infection did in fact exist. As such, it proves extremely difficult for the applicant to rely on these data or for you as regulators to accept their findings as robust.
     
  2. A recent study led by Public Health England and in collaboration with Oxford Immunotec has attempted to gauge the levels of immunity to the SARS-CoV-2 coronavirus, specifically with regards T-cell immunity. As reported in the UK’s Telegraph newspaper[5] the researchers discovered that of the approximately 3000 participants, close to one in four may already be immune to SARS-CoV-2, despite never being infected.

    This inferred natural immunity is encouraging and certainly warrants further investigation, although it is not altogether unexpected when considering the family of viruses SARS-CoV-2 is reportedly from.

    These findings should be considered when determining the overall need for a vaccine for COVID-19 and when attempting to determine the intended population.
     
  3. The public hysteria in relation to SARS-CoV-2 and COVID-19 is clear for all to see, however it should not play a role in determining the safety, efficacy and quality of a vaccine, or indeed if such vaccines are warranted.

    The attempts by the mainstream media, lobbyists, the pharmaceutical industry and governments to suggest a vaccine, rolled-out to the entire global population as a solution to ending government-imposed measures such as “lockdown” is unprecedented and potentially both morally and ethically wrong.

    The approval of a vaccine to all age groups is perhaps not a first, however when factored alongside the use of untested new technology in mRNA vaccines and the limited amount of safety and efficacy testing should be a colossal factor when determining any licensing to the wider-population post-phase III.


Ultimately, the decision to approve or reject any application for a COVID-19 vaccine rests in your hands, however I urge you to consider all the above additional factors when making your decision.

To filter out the noise and not succumb to the pressure being, in my opinion unfairly, applied to you is a considerably difficult task. I am hopeful that you are up to this task, and I strongly request that if you feel at all compromised or unable to carry out this task due to such pressures you take the correct course of action and discharge yourself from such duties.

I wish you all strength, courage and best wishes.


Kind regards
For and on behalf of Independent Pharma Consultants:

 

Nicholas Wells
Managing Director and Regulatory Consultant

[1] http://www.gde.mj.pt/jtrl.nsf/33182fc732316039802565fa00497eec/79d6ba338dcbe5e28025861f003e7b30

[2] https://1drv.ms/b/s!AnRnK7BZ6HTZzRi4EUGcTf74Tt7x?e=psRaHc (Shortened Microsoft OneDrive link)

[3] https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1491/5912603

[4] https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30453-7/fulltext

[5] https://www.telegraph.co.uk/news/2020/11/19/many-could-immune-covid-despite-never-having-infected-study/

N W

Author

Nicholas Wells

Date Published

23rd November 2020

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