The development of safe and highly effective vaccines starting long before the 20th century has been one of medicine’s greatest achievements. The prominent scars on the arms of billions of people (including the left arm of the author) are a constant personal reminder of the success of our ability to curb some of the deadliest diseases from smallpox, TB, measles, mumps and rubella to name but a few. Collectively traditional vaccines are estimated to save approximately 4-5 million lives per year globally. 
It is therefore not surprising that there was optimism at the announcement of a number of randomised controlled trials suggesting excellent efficacy of various vaccines against covid 19 towards the end of 2020. The author himself volunteered to help in a vaccine centre and was one of the first to receive two doses of Pfizer mRNA jab in January 2021. A few weeks later he was asked to go on Good Morning Britain to help discuss and tackle vaccine hesitancy amongst ethnic minority groups after film director Gurinder Chadha OBE admitted that the author had convinced her that the vaccine was very safe and effective.  But since that time there has been considerable evolution in the understanding of the true effectiveness and safety of the covid vaccines that were given emergency use authorisation. This editorial attempts to address some key facts to help others think more critically about what the totality of evidence reveals, what pertinent questions remain unanswered, and how we can constructively move forward. Although the principles under discussion are relevant to all covid 19 vaccines and other pharmacotherapies the emphasis here is more specifically on the BioNTech/Pfizer mRNA product because in western countries that is what has been most widely utilised and continues to be recommended as a booster for the majority of the adult population.
“Science” of the Covid-19 Vaccine
First, what was reported in the mainstream news as being 95% effective against infection was in fact relative risk reduction, not absolute risk reduction from the double blind randomised controlled trial that took place during the more lethal circulating post-Wuhan ancestral strain of the virus. That specific NEJM paper which underpinned the emergency use authorisation of the Pfizer mRNA vaccine actually revealed an absolute risk reduction (ARR) of 0.84%. In other words, for every 119 individuals vaccinated one person would be protected from being infected. (3) (4)
The ARR however depends on the degree of community spread and in principle could affect the degree of spread either upward or downward, since vaccination induces behavioural changes that might increase infection risk, especially if the biological protection provided versus infection is incomplete.
Furthermore, as newer and thankfully, less lethal, mutated strains became dominant, any protection against infection at the very least became less effective and likely completely ineffective, even if there is some significant (as yet to be fully determined in absolute individual terms) protection against serious illness and death.
Before interpreting the reliability of subsequent lower quality observational studies it’s crucial to acknowledge that the highest quality evidence available at the time of drug regulatory approval from phase III double blind randomised controlled did not reveal any statistically significant reduction in either all-cause mortality nor a reduction in covid-19 mortality over a six-month period. (4)
Media’s influence on perceptions of benefit
The director of the CDC Rochelle Walensky recently admitted in an interview that her initial optimism for the vaccine came from a CNN news report. (5) Prior to the overturning of the NHS staff vaccine mandate one very senior health policy leader told me that most of his colleagues in NHS leadership roles were also getting most of their information on the vaccine from the BBC, not through their own critical appraisal of the evidence. Unfortunately, most media health stories do not meet criteria for accuracy. Specifically, in relation to drugs and devices the majority of such reports are rated unsatisfactory in 5 of 10 review criteria: costs, benefits (exaggerated reporting of benefits by use of relative, not absolute risk terms), harms, quality of the evidence and comparison of the new approach with alternatives. (6) It’s instructive to note that in 2009 a World Health Organisation bulletin stated that “It is an ethical imperative that doctors understand the difference between relative and absolute risks to protect patients from unnecessary anxiety and manipulation”. (7) This recommendation was reinforced by the Academy of Medical Royal Colleges in 2015. (8)
The author’s own enthusiasm of the efficacy of the mRNA jab was reinforced in March 2021 (more than two months from receiving the second dose) when he tweeted to 70,000 followers that both himself and his father tested positive for antibodies. But how many doctors are aware that antibodies are an unreliable surrogate for clinical effectiveness? From May 2021 the FDA’s own website has stated that “results from currently authorised SARS-CoV-2 antibody tests should not be used to evaluate a person’s level of immunity or protection from Covid-19 at any time, and especially after the person received a COVID-19 vaccination”. (9)
Emergence of new evidence and unanswered questions
A recent pre-print publication (not yet peer reviewed) co-authored by some of the most eminent and trusted medical scientists in the world in relation to data transparency, including Stanford’s Robert Kaplan and associate editor of the BMJ, Peter Doshi, leaves us asking more troubling questions than providing answers. Accessing data from the FDA and Health Canada websites, and combining results from journal articles that published the Pfizer and Moderna trials , the authors concluded that the absolute risk of a serious adverse event from the mRNA vaccines (a rate of 1 in 800), exceeded the risk reduction in covid-19 hospitalisation (10).
The world’s most cited medical scientist, Professor John Ioannidis, points out that evidence from observational studies in reference to the effectiveness of the covid vaccines may be “spurious”, with bias being generated by pre-existing immunity, vaccination misclassification, exposure differences, testing, disease risk factor confounding, hospital admission decision, treatment use differences, and death attribution. (11)
Tamiflu provides a sobering example of a drug that was initially deemed to be safe and effective (Britain spent half a billion pounds of tax payers money stockpiling the drug), and after analysing regulatory data, turned out not to be. It took 11 years from when Tamiflu was stockpiled in the US (through a campaign by the BMJ for access to the raw data) for Cochrane researchers to ultimately conclude that the antiviral was no better than paracetamol with a small but significant risk of harm. (12) A lead campaigner responsible for Tobacco control in Australia makes it clear in his advice for researchers and public health advocates: “Careers are often built on lifetime commitment to particular phases of evidence. But if the evidence changes, it is absolutely critical for public trust in the integrity of public health that we acknowledge the facts have changed and, accordingly, that we have changed our minds too.” (13) Today’s medical truth may be tomorrow’s folly.
A crisis of trust
An analysis published earlier this year in BMJ Global Health strongly suggests that vaccine mandates and lack of transparency in public health authorities effectively communicating the reasons behind such policies have had detrimental effects on public trust and vaccine confidence. Such mandates are likely to fuel anti-vaccination activism, reduce compliance with other public health measures “and decrease acceptance to future voluntary influenza or varicella (chickenpox) vaccines”. The paper also highlights that the latest data (published in Lancet Infectious diseases) reveals that once infected there is no significant difference in transmission rates between the vaccinated and unvaccinated which makes any scientific case for mandates illegitimate (14). Given this evidence it cannot be ruled out that a person denied the chance to pursue their profession (such as Novak Djokovic’s US government denial of entry into the country so he can play in the US open) because they are not allowed access to a country or area due to a requirement to have a minimum level of Covid vaccination could sue the relevant immigration authority for unjustified restraint of trade.
It’s concerning that in the UK 8 million people have refused the Covid 19 booster despite record infection rates (15) and perhaps more disturbingly we are now seeing “very worrying” reduced uptake of the MMR vaccine for children for the first time in 10 years. (16) It would be important to understand whether this trend is also being replicated in other countries.
Transparency and responsible sharing is key.
In July 2022, an investigation by The BMJ exposed significant financial conflicts of interest of drug approval regulators involving several countries and regions across the world including the USA, Australia, Europe, Japan, Canada and the UK. (17) At a recent lecture the author delivered at a medical event, senior NHS doctors expressed surprise and concern that the UK’s medical regulator, the MHRA, received most (86%) of its funding from the pharmaceutical industry. According to sociologist Donald Light regulators are “not rigorous, they’re not independent, they are selective, and they withhold data. Doctors and patients must appreciate how deeply and extensively drug regulators can’t be trusted so long as they are captured by industry funding” (17) The inextricable financial links between some Covid19 vaccinations advisory committee members and vaccine manufacturers were previously exposed by the BMJ in 2020. (18)
Rather than encourage transparent debate about the true benefits and potential harms of the covid-19 vaccine as new evidence emerges, those that encourage more critical thinking and adding to the database of relevant knowledge are smeared. As investigative science journalist Paul Thacker has revealed social media “fact checkers” have labelled many (including one of the world’s most respected medical journals) as “spreading misinformation”. (19) This does a huge disservice to doctors, patients and the public who deserve and want full transparency. Historically, one of the ways corporations exert their power, create division and fuel a false narrative in favour of their products is through “opposition fragmentation.” (20) Those public health advocates who, for example, were amongst the first to publish research and/or questioned the narrative that smoking was safe were labelled as peddlers of junk science. This was all fuelled by the PR machinery of Big Tobacco that were able to resist regulation for 50 years since the first links between smoking and lung cancer were published in reputed medical journals by adopting a playbook of planting doubt that cigarettes were harmful, confusing the public, buying the loyalty of bent scientists and even downright denial. (21) The medical community and social media companies should encourage open discussion of sceptical viewpoints, rather than falsely labelling “anti-vax” and/or de-platforming those with no conflicts of interest that ask legitimate questions about the true rate of covid vaccine harms.
Immediate access to the raw data is now imperative
Global vaccine mandates for covid-19 must stop until we have the full data on efficacy of all available vaccines. Legislation that ensures access to the raw data for Pfizer’s mRNA jab for full independent analysis, combined with reliable real world pharmacovigilance evidence (through better use of data from United States Vaccine Adverse Event Reporting System (VAERS) and the United Kingdom’s Yellow card scheme) will allow a more precise and better understanding of the true absolute benefits and harms for different age and risk groups. Although causality cannot be directly inferred it’s concerning that over 150,000 yellow card reports have been filled in the UK for the BionTech/Pfizer vaccine involving almost half a million adverse reactions. (22) Historically only 10% of such events are thought to be reported. (23) In the United States better and more up to date use of the Vaccine Safety Data (VSD) systems would also add value as unlike VAERS that is primarily used to generate hypotheses VSD is structured to carefully compare matched cohorts of vaccinated and unvaccinated individuals. (24) Such comprehensive and complete analyses (done by scientists independent of industry interests such as Centre of Evidence Based Medicine in Oxford) will be useful to public health doctors and policy makers. It would empower doctors to engage in more informed decision making with patients using transparent communication of benefit and risk in absolute terms ahead of the booster roll out in the autumn. This would also help restore trust in the reliability of clinical decision making in relation to all drugs, not just the covid-19 vaccinations.
- Walker G, The NNT Group. Review COVID Analysis 2020 – [Internet]. TheNNT. Available from: https://www.thennt.com/review-covid-analysis-2020/
- Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020 Dec 31;383(27):2603–15.
- Schwitzer G. A Guide to Reading Health Care News Stories. JAMA Intern Med. 2014;174(7):1183–1186. doi:10.1001/jamainternmed.2014.1359
- Gigerenzer G. Making sense of health statistics. Bull World Health Organ2009;87:567.
- Malhotra A, Maughan D, Ansell J, Lehman R, Henderson A, Gray M et al. Choosing Wisely in the UK: the Academy of Medical Royal Colleges’ initiative to reduce the harms of too much medicine BMJ 2015; 350 :h2308 doi:10.1136/bmj.h2308
- Ioannidis JPAFactors influencing estimated effectiveness of COVID-19 vaccines in non-randomised studies. BMJ Evidence-Based Medicine Published Online First: 25 March 2022. doi: 10.1136/bmjebm-2021-111901
- Dyer O. What did we learn from Tamiflu? BMJ 2020; 368 :m626 doi:10.1136/bmj.m626
- Chapman S. Reflections on a 38-year career in public health advocacy: 10 pieces of advice to early career researchers and advocates. Public Health Res Pract. 2015 Mar 30;25(2):e2521514. doi: 10.17061/phrp2521514. PMID: 25848732.
- Bardosh K, de Figueiredo A, Gur-Arie R, et a The unintended consequences of COVID-19 vaccine policy: why mandates, passports and restrictions may cause more harm than good BMJ Global Health 2022;7:e008684.
- Demasi M. From FDA to MHRA: are drug regulators for hire? BMJ 2022; 377 :o1538 doi:10.1136/bmj.o1538
- Thacker PD. Conflicts of interest among the UK government’s covid-19 advisers. BMJ2020;371:m4716. Doi:10.1136/bmj.m4716 pmid:33298559
- Madureira Lima J, Galea S. Corporate practices and health: a framework and mechanisms. Global Health. 2018 Feb 15;14(1):21. doi: 10.1186/s12992-018-0336-y. PMID: 29448968; PMCID: PMC5815179.
- Brownell KD, Warner KE. The perils of ignoring history: Big Tobacco played dirty and millions died. How similar is Big Food? Milbank Q. 2009 Mar;87(1):259-94. doi: 10.1111/j.1468-0009.2009.00555.x. PMID: 19298423; PMCID: PMC2879177
- Rawlins MD. Pharmacovigilance: paradise lost, regained or postponed? The William Withering Lecture 1994. J R Coll Physicians Lond. 1995 Jan;29(1):41–9.
24. McNeil MM, Gee J, Weintraub ES, Belongia EA, Lee GM, Glanz JM, Nordin JD, Klein NP, Baxter R, Naleway AL, Jackson LA, Omer SB, Jacobsen SJ, DeStefano F. The Vaccine Safety Datalink: successes and challenges monitoring vaccine safety. Vaccine. 2014 Sep 22;32(42):5390-8. doi: 10.1016/j.vaccine.2014.07.073. Epub 2014 Aug 6. PMID: 25108215; PMCID: PMC6727851.