:: The WHO announced on 31 December 2020 that is has listed the Pfizer/BioNTech vaccine [Comirnaty COVID-19 mRNA} as the first to receive emergency validation under the WHO Emergency Use listing Procedure [EUL]. WHO is continuing evaluation of other COVID-19 vaccine candidates, and is encouraging other developers to submit their COVID-19 vaccine candidates “for review and assessment.” This emergency validation from WHO “opens the door for countries to expedite their own regulatory approval processes to import and administer the vaccine.”

:: Selected Stringent Regulatory Authorities [SRAs], including the FDA and EMA, have been actively reviewing clinical trial evidence and selectively granting emergency use authorization for the Pfizer-BioNTech vaccine and other COVID-19 vaccines under their respective regulatory mechanisms.

:: Other regulatory authorities – including Russia, China and others not represented on the Stringent Regulatory Authorities [SRAs] list – are also reviewing vaccine candidates and have provided emergency use authorization or licensure for selected vaccines, including those being developed by state-sponsored entities [Sputnik V, etc.]. In many cases, full clinical trial data and evidence has not yet been published in peer-reviewed journals or otherwise. Some of these candidates have Phase III clinical trials underway in various third countries with some vaccine availability now established, and immunization campaigns underway.

:: The COVAX facility continues to secure financial resourcesand, as of December 18, 2020, reported agreements in place to access nearly two billion doses of several promising vaccine candidates, and that these arrangements “will enable all participating economies to have access to doses in the first half of 2021, with first deliveries anticipated to begin in the first quarter of 2021 – contingent upon regulatory approvals and countries’ readiness for delivery.”

:: Most countries are actively planning and exploring sources of COVID-19 vaccine supply to address their requirements supplementing vaccines that COVAX may provide.

:: In the near-term, it seems clear that most COVID-19 immunization campaigns will involve vaccines still under emergency use or emergency listing mechanisms, meaning that these vaccines will not have completed full regulatory approval/licensure by any major regulatory authority or by any SRA. In this sense, they are still investigational.

:: The number of vaccines likely to be available over the next few years – most under EUA/L – will result in a complex and competing set of options for country procurement and deployment, with varying efficacy/safety/ pricing/availability/logistical profiles. In many country contexts, the mix of such options will be confusing at least, and likely further challenge trust and vaccine confidence overall.

:: Adding to this confusion and “noise”, we anticipate the rapid emergence of counterfeit pharmaceuticals presented as effective vaccines, as well as the rise of black markets for vaccines that may have some regulatory review. Interpol and Europol warned this month of a probable “onslaught” of criminal activity linked to Covid-19 vaccines, ranging from online fraud and cybercrime to theft and the sale of fake or substandard doses. Counterfeit vaccines were described as a significant public health threat, “ineffective at best, and toxic at worst.”

:: As the pandemic continues to exert extraordinary stress on economies globally, countries can be expected to procure and deploy a variety of vaccines – some likely not reviewed by any major regulatory authority for EUA/L or licensure. In response to economic stresses, there will likely be instances of nation states initiating mandates and “immunization requirements“ to accelerate economic recovery. In parallel, various commercial and non-commercial organizations/sectors will likely experiment with mandates, immunization certificates, and other controls. Such experimentation will not likely proceed in an organized or coherent fashion.

The Informed Choice/Consent/Assent/Right-to-Refuse Imperative
:: We assert that, in principle, health interventions of any kind can responsibly proceed only with the patient making a meaningful informed choice/consent. This is certainly true of therapeutic interventions where the patient has a diagnosis/condition for which the intervention is indicated. But it is especially true when the intervention is preventive – for example, immunization against an infectious disease [such as COVID-19]. We assert that, in principle, there is a right to refuse a preventive health intervention.

:: The informed choice/consent imperative also applies in instances where unlicensed, unapproved compounds, therapies and vaccines are employed. A growing number of drug developers/manufacturers are making innovative medicines and therapies available through “compassionate use” programs [sometimes termed “expanded access” or “pre-licensure access” programs]. Such programs involve medicines and therapies which have demonstrated sufficient efficacy and safety in their respective clinical development programs to be made available responsibly to respond to otherwise unmet patient need. In most settings where these expanded access programs are active, both the regulatory authority and the developer/manufacturer require formal informed consent, as well as institutional ethics review.

:: We argue that vaccines available under emergency use authorization/listing [EUA/L] meet both conditions above: they are preventive in nature and they are still investigational and unlicensed [with trials continuing in all cases]. In short, there is an imperative to ensure that individuals offered immunization with these vaccines exercise informed choice/consent.

:: Further, we argue that informed choice/consent in this context includes a right-of-refusal to be immunized for any reason or no reason. In what will become a confusing landscape of competing and potentially marginal vaccine options, such refusal might be the most prudent decision in many circumstances.. Such refusal must be accommodated, even if it triggers, out of necessity, other limitations such as quarantine given a specific local rate of infection or similar issues.

:: The right-to-refuse also grounds an imperative to challenge mandates or requirements for vaccination with unlicensed/unapproved COVID vaccines. Whether proposed by government, commercial organizations or by economic sectors [e.g. international flights], we argue that mandates – if ever indicated – cannot be implemented using investigational EUA/L vaccines .

:: We recognize that some country-level emergency use authorization regulations and the WHO EUL procedure do not require formal informed consent [the FDA EUA does not, while, for example, French regulation does]. Some will argue that, however ethically-grounded and whatever the precedent, achieving meaningful informed choice/consent in epidemic/pandemic situations is impractical, or, indeed, impossible. We counter that such binary argumentation represents a failure of imagination. It is not a case of “formal informed consent/45+ pages/legalize” vs. nothing. It is a programmatic challenge to be overcome.

Informed Choice/Consent Involving EUA/L COVID Vaccines – Content and Responsibilities
:: Achieving meaningful informed choice/consent depends on the creation and packaging of information presenting benefits/risks/harms and treatment alternatives as available. We argue that such information must, at minimum:

• be complete and accurate, reflecting the most current science and evidence,
• be concisely written and graphically supported to support limited literacy/numeracy skills and varying reading levels to support comprehension,
• be broadly translated for the diverse populations that will need to be vaccinated,
• identify alternative vaccine options and their current and near-term availability to inform the election and timing of vaccination with any particular COVID vaccine,
• be otherwise supportive of recipients and their caregivers/surrogates in making a well-informed decision to accept or decline any vaccine offered, and,
• be tested widely to gauge understanding, retention and satisfaction.

:: We recognize that the primary responsibility and accountability to develop and deliver such information and ensure informed choice/consent rests with national governments and their ministries/departments responsible for public health. We urge their vigorous and resolute engagement. We also recognize the key role that key national health research institutions with global impact such as the CDC in the U.S. and others must play is developing groundbreaking solutions for this imperative.

:: We assert that national ethics committees [variously titled in different countries] have a special obligation to provide guidance and oversight to ensure that the information provided meets the conditions above and is appropriate to local law and custom. and that informed choice/consent can be freely exercised.

:: We call on media organizations to investigate and report with integrity on the state of COVID-19 disease in their locales and how immunization campaigns are being implemented, with special focus on this informed choice/consent imperative.

:: We believe that civil society organizations [CSOs] of all types have a critical role to play in ensuring that informed choice/consent and the right to exercise refusal is protected and defended.

:: We call on international/multilateral agencies led by WHO, UNICEF, OCHA, IOM and others to articulate guidance, develop content, and implement practical strategies to help ensure informed choice/consent with regard to EUA/L COVID vaccines deployed at global, regional and country level. Further we call on multilateral development banks [MDBs] providing financial support for COVID vaccine procurement and deployment to ensure, through their lending agreements and oversight, such informed choice/consent.

:: Equally, we argue that INGOs and collaborative partnerships helping lead the pandemic response, including Gavi, CEPI, Global Fund; IFRC, ICRC, MSF and others [many of which will be implementing COVID immunization campaigns on the ground] should exercise a parallel responsibly in this regard.

:: We call on manufacturers developing these critical vaccines to exercise their responsibility to limit supply of their vaccine candidates to governments and procurement entities which are committed to ensuring informed choice/consent by the individuals who will be immunized with their products.

Finally, we call on individuals and organizations globally – whatever their role, their mission, or their sector – to join in solidarity to endorse this statement, and to ensure that these imperatives are realized in their local context.

Coda
As important as it is that all have access to safe and effective vaccines as quickly as that can be achieved, it is equally important that such access – where emergency use/listing EUA/L vaccines are involved – proceeds under the safeguards appropriate for use of any unlicensed, unapproved medication, especially a preventive intervention – including informed choice/consent.

As specific COVID-19 vaccines achieve full approval/licensure by major regulatory agencies/SRAs and/or pre-qualification by WHO, the ethical imperatives around their deployment will evolve. This could include issuance of immunization requirements or mandates, which should be undertaken with caution and be proportionate to the severity of pandemic conditions and in the context of other responsible public health measures. As warranted by the evolving pandemic situation, refinements to this statement and appropriate supplemental statements will be developed.

[Updated on 4 January 2021]