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Pigs Don’t Fly and You Cannot Expect Absolutely Safe COVID-19 Vaccines (But You Should Expect a Fair Compensation)

In: European Journal of Health Law
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  • 1 Faculty of Law, University of Macau59193MacauChina
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Abstract

This paper focuses on the COVID-19 vaccines authorised for use in the European Union, and explores the mechanisms in place to control vaccine safety and to compensate injured patients, mainly in the context of European law. Based on these considerations, the paper concludes that the refusal by some potential vaccinees to take the vaccine based on safety concerns is ungrounded and an indication of unrealistic expectations, but that in order to build public trust proper compensation mechanisms should be in place.

Abstract

This paper focuses on the COVID-19 vaccines authorised for use in the European Union, and explores the mechanisms in place to control vaccine safety and to compensate injured patients, mainly in the context of European law. Based on these considerations, the paper concludes that the refusal by some potential vaccinees to take the vaccine based on safety concerns is ungrounded and an indication of unrealistic expectations, but that in order to build public trust proper compensation mechanisms should be in place.

1 Introduction

Whether it comes as a surprise or not, many people do not want to get vaccinated against COVID-19 with the available vaccines1 (this paper uses ‘COVID-19 vaccines’ to refer to the various vaccines approved or under development to protect against the disease caused by the SARS-Cov-2 virus). Vaccination is essential to build herd immunity to control the pandemic, especially considering that 80% of infected individuals are asymptomatic,2 and a significant number of infections (between 40% to 50%) occur before the onset of the first symptoms. Mandatory vaccination3 against COVID-19 has been generally rejected by Governments,4 although it will probably be required in some situations, such as international travel.

There are many reasons for refusing to be vaccinated,5 including religious objections,6 political – legal ‘my body, my choice’ objections,7 safety concerns regarding vaccines in general8 and concerns about the safety of COVID-19 vaccines in particular.9 This paper addresses objections based on the safety (or lack thereof) of COVID-19 vaccines and of vaccines in general, the lack of consistency of such critics and the possible mechanisms to address suspicions and criticism (pharmacovigilance, compensation).

This paper begins by comparing the development and approval of COVID-19 vaccines to those of other vaccines in Europe, as the accelerated process is the basis of some wariness on the part of potential vaccinees. It next explores how adverse reactions to the vaccine are monitored (and potentially prevented) as well as the mechanisms in place to compensate patients who suffer from adverse effects, mainly in the context of European law. The paper concludes with the finding that COVID-19 vaccines are as safe as drugs can be and should not be refused due to their expedited production and approval. This paper aims to demonstrate that COVID-19 vaccines, despite some unavoidable risks, are our best hope to fight the pandemic.

2 Risks Posed by Drugs Are Lower than Those Posed by Alternatives

The first concern people have with vaccines relates to their general safety.10 Many consider vaccines to be more dangerous than the diseases they aim to prevent. In the vast majority of cases, drugs successfully treat disease, relieve pain and even save lives; however, very rarely, they can have dangerous, even fatal effects.11 This is true for all pharmaceuticals, vaccines included.12

Safety, in the context of pharmaceutical products, cannot be described as the total absence of risk. Rather, a drug is considered safe when its risks are tolerable, as concluded based on an analysis of those risks, the drug’s expected benefits and the existing therapeutic alternatives.13 Therefore, before a new vaccine is released onto the market, its possible hazards and expected benefits are considered in a risk assessment.14 This assessment procedure is quite strict, and only a positive assessment will result in approval of the drug for use; however, no drug is without risks,15 as past research has shown.16 Adverse effects are rare17 but unavoidable.18

Myths exist in popular culture – promoted by fake news19 – regarding the adverse effects of vaccines, including allegations that they cause autism, hamper the immune system and lead to myriad life-threatening secondary effects. None of these allegations have scientific support. The best source of information regarding medicine is science,20 not pseudo-science,21 and certainly not fabricated information available on social media,22 where these myths are frequently propagated.

According with scientific experts, those that are not vaccinated are more prone to get infected and, if that happens, they are most likely to get severely ill.23 Vaccines not only prevent the vaccinated from becoming infected but also protect the general population by leading to herd immunity24 and, eventually, to the eradication of the disease. Conversely, according to the WHO, the refusal to vaccinate is one of the greatest health threats of our time.25 Experts also demonstrated that in COVID-19 pandemic herd immunity cannot be achieved through natural infection,26 therefore, the vaccine is our best shot to fight the pandemic.

3 Speedy Development and Approval of COVID-19 Vaccines

When compared with previous vaccines, COVID-19 vaccines seem to have appeared in the blink of an eye. Due to the expedited development of these vaccines, a rumour has emerged that a ‘shortcut’ was taken; this rumour has acted to undermine public confidence in the drugs.27

The research and development of a new vaccine is a lengthy, complex and expensive procedure consisting of several stages.28 In the initial, preclinical phase, new vaccine proposals are identified. Experimental studies investigate a product’s efficacy and its tolerance in animal models, to support further research in humans. Only then may clinical trials begin. The trials are conducted in phases (I, II, III and IV). Each phase must be passed successfully before the trial can proceed to the next phase.29

Phase I is the first study of a vaccine to be carried out in humans; its main objective is to demonstrate the safety of the vaccine and identify the type and extent of immune responses it induces. This study is carried out in a very controlled scenario and involves a limited number of participants (usually no more than 100). Phase II aims to establish the product’s safety and immunogenicity, that is, the vaccine’s ability to stimulate the immune system to produce antibodies. When Phase II is successfully completed, the vaccine is considered efficient and without serious adverse effects. However, Phase II studies are limited to a small group of carefully chosen participants (usually 200 to 500); such a small sample cannot be considered representative of the entire target population. Phase III is the last study phase before a vaccine obtains marketing authorisation (MA), that is, the license to be commercialised. In this case the MA is issued by the European Commission following a positive recommendation from the European Medicines Agency (EMA). To fully evaluate the vaccine’s safety and efficacy, Phase III involves large, randomised, double-blind trials, where half of the participants receive the vaccine and the other half receive a placebo. The vaccine is considered efficient if those receiving it either do not get infected or do not get as infected as the placebo group. Such trials must involve thousands of participants for the results to be meaningful. Only after completing the Phase III study and obtaining the MA will the new vaccine be available to the general population. Phase IV is a post-marketing study (pharmacovigilance) that monitors the vaccine’s performance when used in regular medical practice.30

The MA is granted only if the drug regulatory authority in question is satisfied with the results of the trials showing the quality, safety and efficacy of the product. The MA does not guarantee absolute safety and efficacy, which is an impossible goal regardless of how many studies and clinical trials are performed.31 Despite all precautions taken, serious reactions caused by vaccines continue to be reported.32

Phase III trials of the new COVID-19 vaccines have faced two obstacles: the length of the trials and the number of participants. To adequately test the effects of a vaccine, Phase III trials require that participants be exposed to the virus in question after being inoculated. This phase of vaccine testing is generally quite lengthy, given that thousands of participants must be infected with the virus and that it is not permissible to purposely expose people to a virus. Rather, the medical team must wait for participants to be naturally exposed to and infected by the virus in the normal course of their lives. The pharmaceutical companies developing COVID-19 vaccines have attempted to speed up this process by organizing their clinical trials in communities proven to have higher rates of infection (e.g., Brazil, the UK and South Africa).33 However, the public health crisis posed by the COVID-19 pandemic has imposed unusual time constraints. Whereas most vaccines are developed over 10–15 years, COVID-19 vaccines have been developed and tested in less than one year. The trials also involved a much lower number of participants than is generally required.34 As Vaccines Europe35 wrote in a memo circulated among its members,

The speed and scale of development and rollout do mean that it is impossible to generate the same amount of underlying evidence that normally would be available through extensive clinical trials and healthcare providers building experience.36

At the time this paper was finished (March 2021) four vaccines have been approved in the EU: Comirnaty (MA holder BioNTech Manufacturing GmbH); Moderna (MA holder Moderna Biotech Spain, S.L.), AstraZeneca (MA holder AstraZeneca AB) and Janseen (MA holder Janssen-Cilag International NV).37 They all earned what is known as a conditional marketing authorisation (CMA, regulated in Article 14(7) of Regulation (EC) N. 726/2004 and Regulation (EC) N. 507/2006), a temporary type of MA granted for drugs that seem promising in terms of health benefits but for which there is still insufficient information in terms of safety and efficacy. The CMA is valid for one year and is both renewable and subject to specific conditions that are reviewed annually. The objective is that the absence of data will be addressed in the near future, so that the conditional authorisation may be replaced by a definitive one.38

4 Are These Vaccines ‘Good Enough’?

The approval of any pharmaceutical product involves striking a delicate balance.

The approval process must be demanding enough so that only the safest drugs are selected, but it cannot be so demanding that patients do not have access to new medicines that are essential to their life and well-being.39

In the case of the COVID-19 pandemic, the urgent call for a vaccine has left no option other than to ‘compress’ some of the stages of research. However, some fear that speeding up the process implies a corresponding decrease in the vaccines’ quality and safety.40 Some view the speed of the vaccine development as rash and potentially jeopardising the vaccines’ efficacy and safety41 and fear a corresponding increased likeliness of adverse reactions.42 However, there are several considerations that should enter into an objective assessment of those fears.

First, the results of the clinical trials, which were publicly disclosed and strictly scrutinised by drug regulatory authorities, lay these concerns to rest. These results showed the rates of efficacy to be quite high43 and revealed no significant adverse reactions to the vaccines.44

Second, it is important to note that the scientific community did not begin this research from scratch. In a document from the Irish Department of Health it is said that ‘the genetic sequence/the genetic building blocks of the virus were known in early January’.45 Moreover, the scientists developing the vaccines made use of the extensive knowledge on vaccine production gained with existing vaccines as well as technologies developed before the pandemic, such as during the SARS pandemic.46

Third, flexibility mechanisms already in place were deployed both to develop the new drugs (e.g., parallel studies rather than subsequent ones) and to obtain swift approval (e.g., rolling reviews, which allow data to be reviewed at intervals as they are collected rather than en masse at the end of the data collecting process).47 In the past, other vaccines beneficiated from such speedy mechanisms and, for instance, the Ebola vaccine was developed in five years.48

Fourth, unprecedent efforts were undertaken by pharmaceutical companies, which focused all of their attention on the development of these vaccines, as well as by drug authorities, which dedicated all of their resources to this task.

Finally, the traditional procedure was simply too long. The reduction in the timeframe to develop new drugs is a longstanding request of drug developers and the scientific community. It has even been suggested that the drug approval procedure should end after Phase II of clinical trials, postponing Phase III (together with phase IV) to the post-marketing stage49 as a way to make the process faster, cheaper and more innovative.50 Within the context of the COVID-19 vaccine, experts have pointed out that a traditionally lengthy Phase III trial would not have added much information to what we now know about the vaccines and their performance, due in large part to the fact that clinical trials measure only efficacy (vaccine performance in ideal and controlled circumstances) and not effectiveness (real-world performance).51 ‘Ten years to develop a vaccine is a bad thing’, stated Mark Toshner, Director of Translational Biomedical Research, University of Cambridge.52

5 Assuring Safety and Continuous Monitoring

The fact that the COVID-19 vaccines have been granted CMAs rather than MAs has given rise to suspicion.53 However, the CMA does not indicate lower quality; it simply indicates that the initial authorisation granted by the European Commission is based on less comprehensive data than in the regular procedure.54 Although the risk – benefit assessment of the COVID-19 vaccines was based upon less information than is usual, the assessment was nonetheless positive. A CMA is only granted if it is demonstrated that the immediate availability of the drug outweighs the risk of providing it to patients without the same level of scientific evidence usually requested.55 This assessment takes into consideration the risk – benefit ratio, the capacity of the applicant to provide complete data in the future and the existence of severe, unmet medical needs.56 None of the 30 CMAs granted by the EMA between 2006 and 2016 have been suspended or revoked;57 this shows that although conditional, the evaluation is both proper and appropriately strict. The European Commission has assured the public that these vaccines have not been exempted from the strict safety requirements of EU law for the approval of new pharmaceutical products.58

Moreover, the CMA is not the end of the line for the new vaccines. Aware that the CMA requires more data, the EMA binds manufacturers to special obligations, namely post-approval studies, to provide more comprehensive data.59

In addition to the specific monitoring inherent to CMAs, every approved drug submits to pharmacovigilance mechanisms whose aim is to ‘collect information useful in the surveillance of medicinal products, with particular reference to adverse reactions in human beings, and to evaluate such information scientifically’ (Article 102 of Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use). Pharmacovigilance is intended to ‘keep an eye’ on new vaccines and to remove from the market any vaccines that prove to be too risky.60 The European Union (EU) has created its own pharmacovigilance plan, called the ACCESS project (which stands for the vACcine Covid-19 monitoring readinESS project), which ‘focuses on data sources and epidemiological methods to monitor the safety, effectiveness and coverage of COVID-19 vaccines’.61 The plan involves pharmacovigilance conducted by the sponsor, independent data collection and analysis provided by the EU national competent authorities, as well as the intervention of the European Centre for Disease Prevention and Control (ECDC) and the EMA, working jointly.62

6 Compensation for Harmed Patients

6.1 Clauses Excluding the Manufacturer Liability

A further cause of failing public trust in COVID-19 vaccines is the fact that pharmaceutical companies have requested liability exceptions for the vaccines. The advanced purchase agreements between the EU and the pharmaceutical companies contain such clauses (although the agreements have not been made public due to confidentiality clauses).63 This may be interpreted as the companies’ recognition that their products are not as reliable (i.e., safe and effective) as they should be.

However, these clauses can equally be interpreted as a defensive manoeuvre against a potentially high number of lawsuits resulting from the unprecedentedly large-scale vaccination. Even if adverse reactions to the vaccines are rare, as the number of vaccinations grows, the likelihood of such reactions also increases. A recent study published in the British Medical Journal predicted a target population of roughly 5.2 billion people,64 which may give raise to many adverse drug reactions, even if the drug is considered a very safe product according to accepted standards.65 This is not a novel concept. It is a longstanding claim of the International Federation of Pharmaceutical Manufacturers and Associations (a global pharmaceutical industry lobbying group) that in pandemic scenarios vaccines manufacturers should have a liability shield.66

Moreover, because of the pandemic crisis, manufacturers were under pressure to present a reasonably safe and efficient product as soon as possible. They managed to do it in a record time, but because phase III was substantially reduced pharmaceutical companies did not have the time period they usually have to analyse the drug’s performance. ‘The manufacturers should not be unfairly burdened with the additional regulatory risks should the vaccine be desired earlier than normal status quo to deal with the global pandemic’.67

The exemption from liability should not be total but merely partial. This seems more reasonable, given how much pharmaceutical companies stand to profit from these vaccines. The companies could finance their defence by a per-dose tax, as suggested by Halabi, Heinrich and Omer.68 The current solution of total exemption grants pharmaceutical companies excessive profit and undermines accountability. Nonetheless, the alternate solution of holding the manufacturers accountable under standard liability laws would also be unfair, as pharmaceutical companies would have the full burden of compensating injured plaintiffs (potently millions of them) for unfortunate events, which the company cannot control nor anticipate, no matter how many precautions are taken. Ultimately, this solution could endanger public health by discouraging pharmaceutical companies from investing in this crucial research.69

Aware that vaccines are very ‘tricky’ products in terms of consumer protection, many jurisdictions (those in Europe include Austria, Denmark, Finland, France, Germany, Hungary, Iceland, Italy, Luxembourg, Norway, Russia, Latvia, Slovenia, Sweden, Switzerland and the UK) have no-fault compensation schemes in place for routine immunisation; these do not specifically address health crisis situations but could potentially be interpreted to include them.70

Moreover, the WHO has an insurance mechanism in place to address injuries resulting from vaccines used in health crises.71 There are reports of a special scheme created by COVAX (co-led by WHO and Gavi, the Vaccine Alliance) to assist poor nations in this regard by means of a no-fault compensation scheme, co-funded by public entities and the private sector.72

At the time of writing this paper, compensation for parties injured by the COVID-19 vaccines is still blurred in many jurisdictions. Two types of potential injuries are at stake here: adverse events caused by immunisation (lack of safety) but also infection with COVID-19 in spite of the immunisation (lack of efficiency).

6.2 Some Solutions From non-EU Jurisdictions

In the US exclusion of liability resulting from vaccine injuries is a solution long established by the National Childhood Vaccine Injury Act of 1986 (NCVIA), which set up the Vaccine Injury Compensation Program (VICP), as a reaction to the increase in litigation based on claims against the Pertussis vaccine. The aim was to reduce litigation and protect manufactures, which indeed happened, but only for a limited number of injuries.

Within the current health crisis the US government has negotiated with several pharmaceutical companies, granting them immunity from liability for adverse drug reactions, based on a 2005 law, the Public Readiness and Emergency Preparedness Act,73and providing legal protection to pharmaceutical companies until 2024.74 A fund has been established in the US to compensate people ‘who suffer serious adverse events from covered diagnostic devices, medications, or therapies used to identify, prevent, or treat certain conditions’.75 However, the fund – the Countermeasures Injury Compensation Program (CICP) – does not work properly.76 On the other hand, suing the government agency that approved the vaccine, the US Food and Drug Administration, is not an option due to the principle of sovereign immunity.77 This may leave injured patients without recourse.

The UK followed a similar path. Several decades ago, in the aftermath of the Pertussis vaccine incident, the UK issued the Vaccine Damage Payments Act 1979 (VDP Act), creating a national fund to compensate people injured by immunisation.78 It only covers specific vaccines (rectius, specific diseases), but on December 2020 the British Department of Health and Social Care added COVID-19 to the list,79 through the Vaccine Damage Payments (Specified Disease) Order 2020.80 There are, however, some loopholes in this solution.81 First, the VDP Act only covers ‘severe disablement’, understood as, as least, 60% disablement, a very hight threshold, not easily reached. Secondly, as the VDP Act requires causation to be demonstrated, several claims fail to succeed.82 Thirdly, even the ones that do succeed might be frustrated with the compensation: £120 000, a value that might leave some applicant undercompensated.

6.3 The EU Solution … Do We Have One?

In the EU, the European Commission has stated that the existing law governing product liability – Directive 85/374/EEC (hereafter, the Directive)83 which is based on strict liability to best protect the consumer against safety hazards – will still be applicable (‘In line with EU product liability rules, liability remains with the company’).84 There is, however, a significant caveat: governments (or, eventually, the EU) will have to compensate pharmaceutical companies for expenses incurred in compensating consumers (‘the APAs [Advanced Purchase Agreements] provide for Member States to indemnify the manufacturer for possible liabilities incurred only under specific conditions set out in the APAs’).85 The exact conditions and mechanisms for manufacturer compensation by the government remain to be clarified.

Harmed EU patients will have to resort to the court for compensation. Furthermore, they are not guaranteed compensation in all situations.

First of all, as the directive is based on strict liability, culpability is not required to be demonstrated in court; however, causation is (Article 4 of the Directive), and this can be very difficult to establish.86 In general, causation is difficult to assess as it pertains to drugs,87 and moreover to vaccines.88 Two special difficulties arise: (i) to prove causation regarding injuries that took place some time (even years) after inoculation (leaving the possibility of many possible causes);89 (ii) to prove that an inoculated person got infected despite the vaccine and thus that the vaccine is a defective product providing inadequate protection.90

Secondly, the Directive list in its Article 7 some circumstances that can be argued by the manufacturer to be exempted from liability, including when ‘the state of scientific and technical knowledge at the time when he put the product into circulation was not such as to enable the existence of the defect to be discovered’ (Article 7(e)). The novelty of the virus and the lack of scientific knowledge about it could ground this exception in court.

A lack of uniformity on the application of the of the Directive to injuries resulting from COVID-19 vaccines is a real possibility. Being a Directive, it does allow a margin of discretion for member States to implement content in their national laws. Different solutions are in place in EU countries and different interpretation from national courts are frequent.91

A possible solution is to create a legal framework to deal with the health crisis uniformly within the EU, creating an emergency found sponsored by the EU and the member states.92 Injured patient would receive a lump sum, most likely less than the real value of the injury, but with the advantage of avoiding litigation, with all negative outcomes derived from it (increased costs, time consuming). This model, similar to the ones already in place in several EU jurisdiction, seems the most viable option. However, the last position of the EU Commission was silent in this regard and only mentioned the Directive.

7 A Societal Contract: Some Risk in Exchange for Public Health Protection

We, as a community, must realise that the COVID-19 vaccines, as any other drug, can never be absolutely safe.93 Drugs necessarily entail adverse reactions, and the likelihood of adverse effects is only heightened in the context of mass vaccinations by a product approved on the basis of less information than usual (although the extent of the effect of the expedited approval process is unknown).

Nevertheless, there is no better alternative given the present limitations. Faced with a pandemic that, as of January 2021, has killed 2.6 million people worldwide and infected 100 million – the majority of whom have recovered but often with sequelae, the effects of which are still unknowable,94 we simply do not have the time to ‘wait and see’. It is important to distinguish ‘less data’ from ‘no data’ or ‘negative data’. Public trust in vaccines must be bolstered.95

To be inoculated is a matter of individual good (individual health) but above all a matter of public good (public health), and the latter clearly surpasses any potential negative effect for the individual. In the words of Xue and Ouellette,

Consumption of a vaccine benefits not only the vaccinated patient but also the people around them, leading to an aggregate social benefit that is greater than the sum of all individual benefits (…) some people will choose not to be vaccinated, believing that their private costs outweigh their private benefits, even though the social benefits of their being vaccinated exceed the social costs.96

We are faced with a new type of social contract whereby we, as a society, must all agree to take the vaccine, even knowing that some of us will suffer adverse reactions to it. We cannot predict who will be harmed by the vaccine, but it is nonetheless an unavoidable risk. Thus, adequate compensation should be made available to those severely harmed when fulfilling their part of the societal contract. If suing the pharmaceutical company is excluded (as in the US), adequate compensation mechanisms should be provided, most likely based on the socialisation of risk funds, a solution that is compatible with the idea of the social contract as a basis for mass vaccination. The social contract’s aim is to preserve human lives threated by a serious health crisis, and thus the community must take the risk (inherent to any vaccine) based on our all belonging to humankind.

8 Realistic Expectations (or: Pigs Do not Fly)

The refusal to be inoculated probably arises from unrealistic expectations regarding vaccines in general and these vaccines in particular. Vaccines are among the greatest public health achievements of modern times,97 but they have flaws.

It is not guaranteed that all fully elucidated people will agree to be vaccinated. However, clear information remains the best tool98 to address a lack of trust in the government and in public health authorities,99 particularly as regards the expedited development and approval of the COVID-19 vaccines. Education should highlight the benefits of the vaccines as well as explain their potential hazards. Prospective consumers should be informed of the particularities of the vaccines’ speedy development and approval and how these have affected or may affect the expected benefits of the vaccines (if at all). People should also be made aware of possible adverse reactions. The alternative scenarios, including spread of the virus, increase in mortality rate and further lockdowns, are essential information to a well-considered analysis. People have the right to make an informed decision based on all the facts, including the potential safety hazards. Speedy compensation must be guaranteed for the injured ones, not only for fairness but also to reinforce public trust.100

Above all, expectations must be realistic. A vaccine is not a magic potion; no vaccine can provide 100% protection against infection, and some individuals will have serious adverse reactions to any drug that science cannot avoid. Although not a magic potion, however, vaccines are the next best thing.

Acknowledgement

This study was funded by the Shenzhen Institute of Advanced Technology, Chinese Academy of Science (Project No. CP-030-2021) and by the University of Macau Multi-Year Research Grant MYRG2019-00035-FLL. Title of the project: Legal and Regulatory Issues Associated with Synthetic Biotechnology (Biosafety).

1

R. Tucker, ‘Approximately a Fifth of People Across the World Would Refuse a COVID-19 Vaccine’, Hospital Healthcare Europe (14 December 2020), available online at https://hospitalhealthcare.com/covid-19/approximately-a-fifth-of-people-across-the-world-would-refuse-a-covid-19-vaccine/ (retrieved 20 January 2021).

2

C. Heneghan, J. Brassey and T. Jefferson, ‘COVID-19: What Proportion Are Asymptomatic?’, Centre for Evidence-Based Medicine (6 April 2020), available online at https://www.cebm.net/covid-19/covid-19-what-proportion-are-asymptomatic/ (retrieved 2 January 2021).

3

In a recent paper, Julian Savulescu (J. Savulescu, ‘Good Reasons to Vaccinate: Mandatory or Payment for Risk?’ Journal of Medical Ethics 47 (2021) 78–85) advocated for mandatory vaccination, carrying a penalty for noncompliance in the form of a payment (in cash or in kind).

4

M. Rodriguez Martinez, ‘Will any Countries in Europe Make the COVID Vaccine Compulsory?’, Euronews (7 December 2020), available online at https://www.euronews.com/2020/12/07/will-any-countries-in-europe-make-the-covid-vaccine-compulsory (retrieved 15 February 2021).

5

A. Kitta and D.S. Goldberg, ‘The Significance of Folklore for Vaccine Policy: Discarding the Deficit Model’, Critical Public Health 27(4) (2017) 506–514, doi: 10.1080/09581596.2016.1235259.

6

G. Pelčić, S. Karačić, G.L. Mikirtichan, O.I. Kubar, F.J. Leavitt, M. Cheng-Tek Tai, N. Morishita, S. Vuletić and L. Tomašević, ‘Religious Exception for Vaccination or Religious Excuses for Avoiding Vaccination’ Croatian Medical Journal 57(5) (2016) 516–521, doi: 10.3325/cmj.2016.57.516.

7

J.A. Reich, ‘Neoliberal Mothering and Vaccine Refusal: Imagined Gated Communities and the Privilege of Choice’, Gender and Society 28(5) (2014) 679–704.

8

N.E. MacDonald, ‘Vaccine Hesitancy: Definition, Scope and Determinants’, Vaccine 33 (2015) 4161–4164.

9

N.M. Pace and L. Dixon, ‘COVID-19 Vaccinations (Liability and Compensation Considerations Critical for a Successful Campaign)’, Rand Corporation (September 2020), available online at https://www.rand.org/pubs/perspectives/PEA761-1.html (retrieved 20 February 2021).

10

MacDonald, supra note 8.

11

V.L. Raposo, ‘Safe Drugs Versus Innovative Drugs (Can We Have Both?)’, Advanced Pharmaceutical Bulletin 10(3) (2020) 334–337. Doi:10.34172/apb.2020.041.

12

F. Destefano, P.A. Offit and A. Fisher, ‘Vaccine Safety’, Plotkin’s Vaccines (2018) 1584–1600.https://doi.org/10.1016/B978-0-323–35761-6.00082-1.

13

V.L. Raposo, Danos Causados por Medicamentos – Enquadramento Jurídico à Luz do Ordenamento Europeu (Coimbra: Almedina, 2018).

14

H. Arlegui, K. Bollaerts, F. Salvo, V. Bauchau, G. Nachbaur, B. Bégaud and N. Praet, ‘Benefit – Risk Assessment of Vaccines. Part I: A Systematic Review to Identify and Describe Studies About Quantitative Benefit – Risk Models Applied to Vaccines’, Drug Safety 43 (2020) 1089–1104, doi: 10.1007/s40264–020–00984–7.

15

R. Kwok, ‘Vaccines: The Real Issues in Vaccine Safety’, Nature 473 (2011) 436–438, doi: 10.1038/473436a.

16

S. Bhattacharyya, A. Vutha and C.T. Bauch, ‘The Impact of Rare But Severe Vaccine Adverse Events on Behaviour-Disease Dynamics: A Network Model’, Science Reports 9 (2019) 7164, doi: 10.1038/s41598–019–43596–7.

17

Ibid.

18

E. Wertheimer, ‘Unavoidably Unsafe Products: A Modest Proposal’, Chicago-Kent Law Review 71 (1996) 189–217. See also G. Millward, A Disability Act? The Vaccine Damage Payments Act 1979 and the British Government’s Response to the Pertussis Vaccine Scare, Social History of Medicine 30(2) (2017) 429–447, doi: 10.1093/shm/hkv140, about adverse events involving vaccines.

19

N.A. Atehortua and S. Patino, ‘COVID-19, a Tale of Two Pandemics: Novel Coronavirus and Fake News Messaging’, Health Promotion International (2020), doi: 10.1093/heapro/daaa140.

20

S. Geoghegan, K.P. O’Callaghan and P.A. Offit, ‘Vaccine Safety: Myths and Misinformation’ Frontiers in Microbiology 11 (2020) 372, doi: 10.3389/fmicb.2020.00372; J.P. Goullé and L. Grangeot-Keros, ‘Aluminum and Vaccines: Current State of Knowledge’, Médicine et Maladies Infectueuses 50(1) (2020) 16–21; V. Vetter, G. Denizer, L.R. Friedland, J. Krishnan and M. Shapiro, ‘Understanding Modern-Day Vaccines: What You Need to Know’ Annals of Medicine 50(2) (2018) 110–120, doi: 10.1080/07853890.2017.1407035.

21

Geoghegan, O’Callaghan and Offit, supra note 20.

22

A. Kata, ‘A Postmodern Pandora’s Box: Anti-Vaccination Misinformation on the Internet’, Vaccine 28 (7) (2010) 1709–1716.

23

K. Moodley, K. Hardie, M.J. Selgelid, R.J. Waldman, P. Strebel, H. Rees and D.N Durrheim, ‘Ethical Considerations for Vaccination Programmes in Acute Humanitarian Emergencies’, Bulletin of the World Health Organization 91 (2013) 290–297, doi: 10.2471/BLT.12.113480.

24

P.E. Fine, ‘Herd Immunity: History, Theory, Practice’, Epidemiology Reviews 15 (1993) 265–302; G. Gonçalves, ‘Herd Immunity: Recent Uses in Vaccine Assessment’, Expert Review of Vaccines 7 (10) (2008) 1493–1506, doi: 10.1586/14760584.7.10.1493.

25

World Health Organization, ‘Ten Threats to Global Health in 2019’, available online at https://www.who.int/news-room/feature-stories/ten-threats-to-global-health-in-2019 (retrieved 23 November 2020).

26

Imperial College COVID-19 Response Team, Impact of non-pharmaceutical interventions (NPIs) to reduce COVID-19 mortality and healthcare demand, doi: 10.25561/77482; H.E. Randolph and L.B. Barreiro, Herd immunity: Understanding COVID-19. Immunity 52 (2020) 737–741, doi: 10.1016/j.immuni.2020.04.012.

27

D. Chow, ‘Will the Covid Vaccine Be Safe? What the Scientists Want to See’, NBCnews (21 November 2020), available online at https://www.nbcnews.com/health/health-news/will-covid-vaccine-be-safe-what-scientists-want-see-n1248466 (retrieved 5 February 2021).

28

K. Singh and S. Mehta, ‘The Clinical Development Process for a Novel Preventive Vaccine: An Overview’, Journal of Postgraduate Medicine, 62(1) (2016) 4–11, doi: 10.4103/0022–3859.173187.

29

About the development of clinical trials under european law, T. Lalova, A. Negrouk, A. Deleersnijder, P. Valcke and I. Huys, ‘Conducting Non-COVID-19 Clinical Trials during the Pandemic: Can Today’s Learning Impact Framework Efficiency?’, European Journal of Health Law 27 (2020) 425–450. I. De Miguel Beriain, T. Minssen, T. Chortara, A. Duardo-Sànchez, O. Feeney, H. Felzmann, E. Fernández de Uzquiano, E. Lievevrouw, L. Marelli, T. Mattsson, E. Pulice, V.L. Raposo, J. Robienski, S. Penasa, I. Van Hoyweghen and J.R. Hermann, ‘An EU Comparative Analysis of the Regulation of Clinical Trials Supervisory Bodies in the Aftermath of Regulation 536/2014’, European Public Law, 26(2) (2019) 307–330.

30

International Federation of Pharmaceutical Manufacturers & Associations, ‘The Complex Journey of a Vaccine’ (2019), available online at https://www.ifpma.org/wp-content/uploads/2019/07/IFPMA-ComplexJourney-2019_FINAL.pdf (retrieved 4 January 2021).

31

Raposo, supra note 11, 335–336.

32

M.K. Smatti, A.A. Al Thani and H.M. Yassine, ‘Viral-Induced Enhanced Disease Illness’, Frontiers in Microbiology 9(5) (2018), doi: 10.3389/fmicb.2018.02991.

33

M. Voysey, S.A. Clemens, S.A. Madhi, L.Y. Weckx, P.M. Folegatti, P.K. Aley, et al., ‘Safety and Efficacy of the ChAdOx1 nCoV-19 Vaccine (AZD1222) against SARS-CoV-2: An Interim Analysis of Four Randomised Controlled Trials in Brazil, South Africa, and the UK’, Lancet 397 (10269) (2020), doi: 10.1016/S0140–6736(20)32661–1.

34

There were 44 000 participants enrolled in clinical trials for the Pfizer – BioNTech vaccine, 30 000 for Moderna vaccine and 30 000 for AstraZeneca.

35

This is a specialised vaccines group within the European Federation of Pharmaceutical Industries and Associations (EFPIA) (Vaccines Europe, https://www.vaccineseurope.eu/about-us), that represents drugmakers including AstraZeneca, GlaxoSmithKline, Janssen (which belongs to Johnson & Johnson), Merck, Novavax, Pfizer, Sanofi,Takeda, Abbott and CureVac.

36

D.P. Mancini and M. Peel, ‘Covid-19 Vaccine Makers Lobby EU for Legal Protection’, Financial Times (26 August 2020), available online at https://www.ft.com/content/12f7da5b-92c8-4050-bcea-e726b75eef4d (retrieved 14 December 2020).

37

European Medicines Agency, Treatments and Vaccines for COVID-19: Authorised Medicines (2021), available online at https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/treatments-vaccines/treatments-vaccines-covid-19-authorised-medicines(accessed 23 February 2021).

38

J. Hoekman, W. Boon, J. Bouvy, H. Ebbers, J. de Jong and M. De Bruin, ‘Use of the Conditional Marketing Authorization Pathway for Oncology Medicines in Europe’, Clinical Pharmacological Therapy 98 (2015) 534–541, doi: 10.1002/cpt.174.

39

Raposo, supra note 13, 334.

40

P.N. Newton, K.C. Bond, on Behalf of 53 Signatories from 20 Countries, ‘COVID-19 and Risks to the Supply and Quality of Tests, Drugs, and Vaccines’, The Lancet Global Health 8(6) (2020) E754–E755, doi: 10.1016/S2214–109X (20) 30136–4.

41

Torreele (E. Torreele, ‘The Rush to Create a Covid-19 Vaccine May Do More Harm than Good’, British Medical Journal 370 (2020) m3209) expressed concern, before the results of the first clinical studies were released, that the vaccines would show ‘only 30% efficacy or a durability of only months’.

42

K. Van Tassel, C. Shachar and S. Hoffman, ‘Covid-19 Vaccine Injuries – Preventing Inequities in Compensation’, The New England Journal of Medicine (2021), doi: 10.1056/NEJMp2034438.

43

95% reduction in the number of symptomatic COVID-19 cases for Comirnaty (European Medicines Agency, supra note 37); ‘Moderna vaccine has been shown to have an efficacy of approximately 92 per cent in protecting against COVID-19, starting 14 days after the first dose’ (World Health Organization, The Moderna COVID-19 (mRNA-1273) Vaccine: What you Need to Know (26 January 2021), available online at https://www.who.int/news-room/feature-stories/detail/the-moderna-covid-19-mrna-1273-vaccine-what-you-need-to-know?gclid=Cj0KCQiAx9mABhD0ARIsAEfpavRuSxFsBFFfCKoj7BCKd2sySaAzOJXV3j0aD-mXx-R4ej2deVEksroaAnF_EALw_wcB) (retrieved 19 February 2021); for AstraZeneca, efficacy was 62.1% participants who received two standard doses, and 90% for participants who received a low dose followed by a standard dose’ (Voysey, Clemens, Madhi et al., supra note 33).

44

CDC COVID-19 Response Team and Food and Drug Administration, ‘Allergic Reactions Including Anaphylaxis After Receipt of the First Dose of Moderna COVID-19 Vaccine – United States, December 21, 2020 – January 10, 2021’, MMWR Morbidity Mortal Weekly Report 70 (2021) 125–129, doi: 10.15585/mmwr.mm7004e1external icon; European Medicines Agency, supra note 37.

45

Department of Health and Human Services, ‘Declaration Under the Public Readiness and Emergency Preparedness Act for Medical Countermeasures Against COVID–19’, Federal Register 85 (52) (2020) 15198–15203.

46

Ibid.

47

That is, instead of leaving the reviewer process to the very end, when all necessary data to request the MA are gathered, reviews can take place as data are being collected, so when the MA is finally requested the reviewer process is already on.

48

J. Wolf, S. Bruno, M. Eichberg, R. Jannat, S. Rudo, S. VanRheenen and B.-A. Coller, ‘Applying Lessons from the Ebola Vaccine Experience for SARS-CoV-2 and Other Epidemic Pathogens’, npj Vaccines 5 (2020) 51, doi: 10.1038/s41541–020–0204–7.

49

P.J. Lachmann, ‘The Penumbra of Thalidomide, the Litigation Culture and the Licensing of Pharmaceuticals’, QJM: An International Journal of Medicine 105(12) (2012) 1179–1189.

50

M.M. Rocha, E.P. Andrade, E.R. Alves, J.C. Cândido and M.M. Borio, ‘Access to Innovative Medicines by Pharma Companies: Sustainable Initiatives for Global Health or Useful Advertisement?’, Global Public Health 15(6) (2020) 777–789, doi: 10.1080/ 17441692.2020.1729391.

51

A.G. Singal, P.D. Higgins and A.K. Waljee, ‘A Primer on Effectiveness and Efficacy Trials’, Clinical and Translational Gastroenterology 5(1) (2014) e45, doi: 10.1038/ctg.2013.13.

52

M. Toshner, ‘Less than a Year to Develop a COVID Vaccine – Here’s why you Shouldn’t Be Alarmed’, The Conversation (25 November 2020), available online at https://theconversation.com/less-than-a-year-to-develop-a-covid-vaccine-heres-why-you-shouldnt-be-alarmed-150414 (retrieved 10 January 2021).

53

R. Banzi, C. Gerardi, V, Bertele and S. Garattini, ‘Approvals of Drugs with Uncertain Benefit – Risk Profiles in Europe’, European Journal of Internal Medicine 26(8) (2015) 572–584.

54

This is not a European specificity, as many jurisdictions have expedited processes of drug approval (S. Simpson, A. Chakrabarti, D. Robinson, K. Chirgwin and M. Lumpkin, ‘Navigating Facilitated Regulatory Pathways During a Disease X Pandemic’, npj Vaccines 5 (2020) 101, doi: 10.1038/s41541–020–00249–5).

55

European Medicines Agency, Guideline on the Scientific Application and the Practical Arrangements Necessary to Implement Commission Regulation (EC) No 507/2006 on the Conditional Marketing Authorisation for Medicinal Products for Human Use Falling Within the Scope of Regulation (EC) No 726/2004, 25 February 2016, EMA/CHMP/509951/2006, available online at https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-scientific-application-practical-arrangements-necessary-implement-commission-regulation-ec/2006-conditional-marketing-authorisation-medicinal-products-human-use-falling_en.pdf (retrieved 20 November 2020); G. Nicotera, G. Sferrazza, A. Serafino and P. Pierimarchi,‘The Iterative Development of Medicines Through the European Medicine Agency’s Adaptive Pathway Approach’, Frontiers in Medicine 6(148) (2019) doi: 10.3389/fmed.2019.00148.

56

Nicotera, Sferrazza, Serafino et al., supra note 55.

57

‘30 conditional marketing authorisations have been granted, of which 11 have been converted into “standard” marketing authorisations, 2 have been withdrawn for commercial reasons and the remaining 17 authorisations are still conditional’ (European Medicines Agency, supra note 55, 2).

58

European Commission, Questions and Answers: Coronavirus and the EU Vaccines Strategy, 24 September 2020, available online at, https://ec.europa.eu/commission/presscorner/detail/en/qanda_20_1662 (retrieved 20 November 2020).

59

European Medicines Agency, supra note 55.

60

Raposo, supra note 11, 335–336.

61

European Medicines Agency, Pharmacovigilance Plan of the EU Regulatory Network for COVID-19 Vaccines, EMA/333964/2020 (2020), available online at, https://www.ema.europa.eu/en/documents/other/pharmacovigilance-plan-eu-regulatory-network-covid-19-vaccines_en.pdf (retrieved 21 January 2021); VAC4EU, Briefing Book, 1 September 2020, available online at https://vac4eu.org/wp-content/uploads/2020/09/Briefing-Bookv0.320200901.pdf (retrieved 5 September 2020).

62

M. Cavaleri, H. Enzmann, S. Straus and E. Cooke, ‘The European Medicines Agency’s EU Conditional Marketing Authorisations for Covid-19 Vaccines’, The Lancet, 397 (10272) (2021) P355–P357, doi: 10.1016/S0140–6736(21)00085–4.

63

European Commission, Questions and Answers, supra note 58.

64

F. Wang, R.M. Kream and G.B. Stefano, ‘Long-Term Respiratory and Neurological Sequelae of COVID-19’, Medical Science Monitor: International Medical Journal of Experimental and Clinical Research 26 (2020) e928996, doi: 10.12659/MSM.928996.

65

S. Halabi, A. Heinrich and S.B. Omer, ‘No-Fault Compensation for Vaccine Injury’, New England Journal of Medicine 383(23) (2020) e125(1)–125(3).

66

Ibid.

67

W. Pors, E. Tjon-En-Fa and F. Peel, ‘A Vaccine for COVID-19: Risks and Liabilities from an International Perspective’, Bird & Bird (February 2021), available online at https://www.twobirds.com/en/news/articles/2020/netherlands/a-vaccine-for-covid-19-risks-and-liabilities-in-international-perspective#section1 (retrieved 1 March 2021).

68

Halabi, Heinrich and Omer, supra note 65.

69

Raposo, supra note 11, 335–336.

70

R.G. Mungwira, C. Guillard, A. Saldaña, N. Okabe, H. Petousis-Harris, E. Agbenu, L. Rodewald and P.L.F. Zuber, ‘Global Landscape Analysis of No-Fault Compensation Programmes for Vaccine Injuries: A Review and Survey of Implementing Countries’, PLoS ONE 15(5) (2020) e0233334. Doi: 10.1371/journal.pone.0233334.

71

Halabi, Heinrich and Omer, supra note 65.

72

Ibid.

73

J.D. Winter, C. Cole and J. Wacholder, ‘Toward a Global Solution on Vaccine Liability and Compensation’, Food And Drug Law Journal, 47 (2019) 1–17.

74

Department of Health and Human Services, supra note 45.

75

Health Resources and Service Administration, Covered Countermeasures (17 April 2017), available online at https://www.hrsa.gov/get-health-care/conditions/counter-measures-comp/cm-prep.html (retrieved 12 December 2020).

76

P.H. Meyers, ‘Fixing the Flaws in the Federal Vaccine Injury Compensation Program’, Administrative Law Review 73(4) (2011) 785–851.

77

M.A. Kotler, ‘Shared Sovereign Immunity as an Alternative to Federal Preemption: An Essay on the Attribution of Responsibility for Harm to Others’, Hofstra Law Review 37(1) (2008) 157–194.

78

Millward, supra note 18.

79

UK Government, Government to add COVID-19 to Vaccine Damage Payments Scheme, December 2020, available online at https://www.gov.uk/government/news/government-to-add-covid-19-to-vaccine-damage-payments-scheme (retrieved 28 January 2021).

80

Vaccine Damage Payments (Specified Disease) Order 2020, 2 December, 2020, available online at https://www.legislation.gov.uk/uksi/2020/1411/made (retrieved 10 January 2021).

81

E. Boulden, ‘The Vaccine Damage Payment Act 1979 and the Coronavirus (COVID-19) Vaccine’, Clinical Negligence Law (22 December 2020), available online at https://clinicalnegligence.blog/2020/12/30/the-vaccine-damage-payments-act-1979-and-the-coronavirus-covid-19-vaccine/ (retrieved 2 January 2021).

82

D. Fairgrieve, S. Holm, G. Howells, C. Kirchhelle and S. Vanderslott, ‘In Favour of a Bespoke COVID-19 Vaccines Compensation Scheme’, Lancet Infectious Diseases (2021), doi: 10.1016/S1473–3099(21)00065–7.

83

Council Directive 85/374/EEC of 25 July 1985 on the approximation of the laws, regulations and administrative provisions of the Member States concerning liability for defective products.

About this Directive and drug related injuries, vide Raposo, supra note 13.

84

European Commission, supra note 58.

85

Ibid.

86

European Commission, Report from the Commission to the European Parliament, the Council and the European Economic and Social Committee on the Application of the Council Directive on the Approximation of the Laws, Regulations, and Administrative Provisions of the Member States Concerning Liability for Defective Products (85/374/EEC) COM/2018/246 final, para. 4 (2018), available online at https://eur-lex.europa.eu/legal-content/en/TXT/?uri=CELEX%3A52018DC0246 (retrieved 2 March 202).

Note that in no-fault system the prove of causation must likewise be done and might also preclude compensation (Mungwira, Guillard, Saldaña et al., supra note 70).

87

D. Fairgrieve, P. Feldschreiber, G. Howells and M. Pilgerstorfer, ‘Products in a Pandemic: Liability for Medical Products and the Fight against COVID-19’, European Journal of Risk Regulation 11(3) (2020) 565–603, doi: 10.1017/err.2020.54; E. Rajneri, J.-S. Borghetti, D. Fairgrieve and P. Rott, ‘Remedies for Damage Caused by Vaccines: A Comparative Study of Four European Legal Systems’, European Review of Private Law 1 (2018) 57–96.

88

V.R. Walker, C.H. Park, P.H. Hwang, A. John, E.I. Krasnov and K. Langlais, ‘A Process Approach to Inferences of Causation: Empirical Research from Vaccine Cases in the USA’, Law, Probability and Risk 12(3–4) (2013) 189–205.

89

See, however, case C621/15 (W and Others, 21 June 2017, ECLI:EU:C:2017:484) involving a patient who had been vaccinated against hepatitis B in 1998, later on started to show symptoms of multiple sclerosis, finally dying in 2011. The plaintiff’s claim was accepted, despite the lack of scientific evidence about the link between the vaccine and the injury. For a critic to this decision see L.R. Smillie, M.R. E.-T. and S.L. Cooper, ‘C-621/15 – W and Others V Sanofi Pasteur: An Example of Judicial Distortion and Indifference to Science’, Medical Law Review 26(1) (2017) 134–145, doi: 10.1093/medlaw/fwx049.

90

Fairgrieve, Feldschreiber, Howells et al., 2020, supra note 87.

91

European Commission, Commission Staff Working Document: Evaluation of Council Directive 85/374/EEC of 25 July 1985 on the Approximation of the Laws, Regulations and Administrative Provisions of the Member States Concerning Liability for Defective Products Accompanying the Document Report from the Commission to the European Parliament, the Council and the European Economic and Social Committee on the Application of the Council Directive on the Approximation of the Laws, Regulations, and Administrative Provisions of the Member States Concerning Liability for Defective Products (85/374/EEC), SWD/2018/157 final, available online at https://eur-lex.europa.eu/legal-content/DA/ALL/?uri=CELEX:52018SC0157 (retrieved 1 March 2021).

92

Similar suggestions in Fairgrieve, Holm, Howells et al., supra note 82; Pors, Tjon-En-Fa and Peel, supra note 67 (the authors suggest a model in which the fund would only operate ‘to vaccines that were administered in the relatively short period between the provisional authorisation and the completion of Phase III’).

93

N. Bar-Zeev and S. Kochhar, ‘Expecting the Unexpected with COVID-19 Vaccines’, The Lancet Infectious Diseases (2020), doi: 10.1016/S1473–3099(20)30870–7; P. Doshi, ‘Will Covid-19 Vaccines Save Lives? Current Trials Aren’t Designed to Tell Us’, British Medical Journal 371 (2020) m4037, doi: 10.1136/bmj.m4037.

94

Wang, Kream and Stefano, supra note 64.

95

P. Brown and M. Calnan, ‘Braving a Faceless New World? Conceptualizing Trust in the Pharmaceutical Industry and its Products’, Health 16(1) (2012) 57–75, doi: 10.1177/1363459309360783; Torreele, supra note 41.

96

Q.C. Xue and L.L. Ouellette, ‘Innovation Policy and the Market for Vaccines’, Journal of Law and the Biosciences 7(1) (2020) lsaa026, doi: 10.1093/jlb/lsaa026.

97

Geoghegan, O’Callaghan and Offit, supra note 20; Vetter, Denizer, Friedland, et al., supra note 20.

98

S. Pennings and X. Symons, ‘Persuasion, not Coercion or Incentivisation, Is the Best Means of Promoting COVID-19 Vaccination’, Journal of Medical Ethics (2021), doi: 10.1136/medethics-2020–107076.

99

J. Citrin and L. Stoker, ‘Political Trust in a Cynical Age’, Annual Review of Political Science 21(1) (2018) 49–70.

100

Fairgrieve, Holm, Howells, et al., supra note 82.

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