Cranmer
The Pfizer vaccine was approved for use by New Zealand’s regulator, Medsafe on 3 February 2021. The development was immediately welcomed by then Prime Minister Ardern who stated, “Medsafe’s decision is the culmination of a rigorous assessment process over many months to ensure the Pfizer/BioNTech vaccine is safe and effective to use here. It is informed by the most up-to-date medical and scientific data. We can have confidence in their decision.”
However, in reality, the government’s representation of Medsafe’s assessment was overstated. Specifically, Medsafe’s clinical assessment found:
- “The duration of the vaccine protection has not been established beyond two months.”
- “At this stage, there is limited evidence of protection against severe disease.”
- “There is no long term safety follow-up information.”
- “Vaccine prevention of asymptomatic infection and disease transmission has not been established.”
Therefore when it made its benefit risk assessment, Medsafe concluded:
The benefit risk balance of Comirnaty (COVID-19 mRNA Vaccine) for active immunisation to prevent coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 in individuals 16 years of age and older, is not clear. At this stage, there is evidence only for short-term protection, and longer-term safety data are lacking. However, experience with the vaccine is accumulating rapidly.
On 10 February 2021, Chris Hipkins, Minister for COVID-19 Response, was advised in a briefing paper from Dr Bloomfield about the limited data on disease transmission. Specifically, Hipkins was advised:
We do not yet have conclusive evidence on the effectiveness of the Pfizer vaccine at preventing or reducing transmission to be confident of the public health value of this vaccination, beyond the individual level. So, unlike testing, which had a clear public health benefit, vaccination at this point in time is expected to reduce risk through a reduction in the likelihood of severity of disease and onward transmission. This may change as more evidence becomes available. However, at this time, mandatory vaccination is unlikely to be a justified limitation of the right to refuse medical treatment under Section 11 of the Bill of Rights Act.
The Approval Process
Initial discussions with Pfizer and Medsafe began in September 2020, including a pre-submission meeting on 24 September between the two parties which discussed a range of clinical and logistical issues at a high level.
Pfizer submitted an application on 21 October for provisional consent under s23 of the Medicines Act with a proposed indication for individuals aged 16 years and over.
The Medsafe team evaluated Pfizer’s application between October 2020 and January 2021 on a “rolling application” basis that allowed Pfizer to submit a total of eight data tranches as and when they became available. During this period, Medsafe was receiving input from the newly formed Covid Vaccine Technical Advisory Group (CV TAG) and the Ministry of Health Science and Technical Advisory Group (STAG).
Medsafe also received information from its Australian equivalent (the Therapeutic Goods Administration (TGA)) which was also considering an application from Pfizer at the same time. The TGA shared tranches of evaluation reports with Medsafe in December and January. Medsafe received a copy of TGA’s final report (granting provisional consent in Australia) on 25 January 2021.
Following the conclusion of the evaluation process, which involved the Medsafe evaluation reports being peer-reviewed, the clinical evaluation, as assessed by Medsafe, was that the benefit risk balance of the vaccine was not clear because of data limitations. It was noted that there were several aspects of the data required to support quality, safety and efficacy that were not available at the time of completion of the evaluation.
On that basis, Medsafe concluded, “Due to the unresolved concerns and additional quality, safety and efficacy data to be provided at the time of completion of the evaluation, Medsafe is unable to recommend that this product be granted consent. It is therefore recommended that the application be referred to the Medicines Assessment Advisory Committee (MAAC) under section 22(2) of the Medicines Act 1981 for their consideration.”
On 28 January 2021, the Group Manager of Medsafe, Chris James, wrote to Pfizer Australia and advised it of his decision:
Having reviewed the information supplied in your initial application and in your further responses, I am not satisfied that I should give my consent to the distribution of the product.
The same day, James referred the application to MAAC writing, “Medsafe is unable to recommend that the Minister’s delegate grant consent to the distribution of the product. You are therefore asked to administer the recommendation that the Minister’s delegate refers this application to the Medicines Assessment Advisory Committee for consideration.”
James advised MAAC that, “Given the rapid development of this medicine and the urgent clinical need that exists in New Zealand, there are several aspects of data to support quality, safety and efficacy that are not available at the time of completion of the evaluation.”
The memo requested that MAAC focus on some specific aspects of the application, including whether there was a positive benefit-risk balance for the vaccine. Medsafe provided MAAC with the relevant documents, including Pfizer’s application dossier, Medsafe’s evaluation reports, the proposed Risk Management Plan, the advice from STAG, and assessment documentation that was provided to Medsafe from the Australian TGA.
MAAC then met on 2 February to consider the application. The minutes do not record MAAC making any independent evaluation of the benefit-risk assessment. When considering the Clinical Evaluation Report prepared by Medsafe which set out the benefit-risk assessment, the minutes from the MAAC meeting record:
However, the clinical picture on efficacy and safety will become clearer over time as more people receive the vaccine.
The Committee discussed the lack of data on the duration of response of the vaccine. Medsafe had asked the sponsor for an early cut-off time for more data, which was not available. The sponsor had confirmed that the next data analysis from the pivotal clinical trial will arrive in April 2021.
Overall, the Committee was satisfied with the clinical report and summary presented. The Committee was satisfied with the efficacy data to date acknowledging that more data will be available over time.
As an aside, MAAC noted, “The data on long terminal half-life of the lipid nanoparticles was considered unusual but unlikely to be a safety concern, as only two doses are intended to be administered.”
However, at that stage, Medsafe had already concluded that booster doses would likely be needed. In its Evaluation of a New Medicine Application (January 2021) which was supplied to MAAC for the purpose of making its assessment, Medsafe stated, “Covid-19 vaccines can be expected not to provide long-term protection – the need for booster doses can be expected.”
Pfizer representatives joined the MAAC meeting and responded to questions from the committee. The minutes note, “The Committee had questions regarding finished product testing, risk of transport to New Zealand, in use data in specific populations, use in severe COVID-19, the emergence of new variants, unforeseen safety signals after the doses given to-date, update on duration of protection and the new 6 dose proposal.” Note that the reference to the ‘new 6 dose proposal’ related to Pfizer’s decision to authorise 6 doses per vial rather than 5 as originally planned (this was later increased to 7 doses per vial).
The day following the MAAC meeting, it issued a memo to Chris James at Medsafe in which it confirmed that it “has recommended that you grant provisional consent to the distribution of the following medicine: Comirnaty (COVID-19 mRNA vaccine).” The memo continued by stating that “you are therefore asked to sign the attached letter to the applicant company to advise them of the outcome of the MAAC recommendation.”
Accordingly, James issued a letter on behalf of Medsafe to Pfizer Australia on the same day confirming the approval of the vaccine for use in New Zealand stating, “The Committee’s recommendation is that I, as the Minister’s delegate, should grant provisional consent to the distribution of the medicine. I agree with the MAAC’s recommendation and a provisional consent notice will be submitted for publication in the New Zealand Gazette.”
Somewhat strangely, although MAAC is a statutory committee under the Medicines Act, it has, since the outbreak of Covid, kept the identity of its members confidential. Requests for details of MAAC’s membership have been refused by the Ministry of Health when requested via the Official Information Act on the basis that they might be harassed. It seems an odd position to take given that the membership of various other advisory groups are known, and that MAAC has played a pivotal role in the approval of the vaccine.
Cabinet Approval
Shortly after approval by Medsafe and MAAC, Cabinet met to make its Decision to Use and to authorise the start of the immunisation program in accordance with its Sequencing Framework. The Cabinet Paper from that meeting stated, “There are limitations of data provided including duration of protection as this is still being determined by ongoing trials.”
Then on 10 February 2021, Chris Hipkins, Minister for COVID-19 Response, received a briefing paper from Dr Bloomfield and another Ministry of Health official titled, Maximising uptake of COVID-19 vaccines in Tier 1. The paper stated:
While we do not yet know the extent to which the vaccines prevent COVID-19 transmission, vaccination is expected to reduce transmission through reducing the severity of disease and therefore the risk of onward transmission. Therefore, COVID-19 vaccination will support other public health measures to reduce the risk of these workforces contracting and spreading the virus. The use of Personal Protective Equipment (PPE), social distancing, and mandatory COVID-19 testing for border staff will still be needed to ensure that people continue to be safe.
…
We can align with the existing framework for the Order. We have already defined this workforce and can use the same definition for COVID-19 vaccination. A key difference is that vaccination, unlike testing, is a medical treatment, which everyone has a general right to refuse under Section 11 of the Bill of Rights Act 1990.
Although vaccination has a beneficial effect on personal health, that does not provide a public health justification for infringing on a right to refuse medical treatment. It is the existence of a threat to wider public health, and a measure that will enhance or preserve it, that is the essential component to justify limiting the right to refuse medical treatments under the Bill of Rights Act.
We do not yet have conclusive evidence on the effectiveness of the Pfizer vaccine at preventing or reducing transmission to be confident of the public health value of this vaccination, beyond the individual level. So, unlike testing, which had a clear public health benefit, vaccination at this point in time is expected to reduce risk through a reduction in the likelihood of severity of disease and onward transmission. This may change as more evidence becomes available. However, at this time, mandatory vaccination is unlikely to be a justifiable limitation of the right to refuse medical treatment under Section 11 of the Bill of Rights Act.
The difference in certainty of the public health value of testing versus vaccination has an impact on how other legislative levers may be used.
However, despite the lack of data supporting the effectiveness of the Pfizer vaccine at preventing or reducing transmission, officials were actively considering whether border workers should be required to be vaccinated by way of legal mandate as far back as February 2021. Bloomfield described this statutory intervention as ‘an additional lever’, but it was not one that he recommended at that time for a variety of reasons. The paper set out the rationale as follows:
Vaccination is a medical treatment and therefore engages Section 11 of the New Zealand Bill of Rights Act – the right to refuse medical treatment. Requiring that some of our workforces be vaccinated will be inconsistent with that right unless it can be demonstrably justified.
The state has a legitimate interest in impeding community transmission of the virus. Section 11 of the COVID-19 Public Health Response Act 2020 (The COVID-19 Act) allows orders to be made for the purpose of “requiring persons to take any specified measures that contribute or are likely to contribute to the preventing the risk of the outbreak or spread of COVID-19”.
Pursuing that objective will be a demonstrated justified infringement on the right to refuse medical treatment if there is a credible, public health-based analysis and evidence that vaccination will impede community transmission or make a substantial contribution to it that cannot be otherwise achieved.
Context is relevant here, as ever. The risk assessment of contracting the virus and therefore risk of onward transmission is highly relevant. For example, the risk profile will be different in respect of the person who meets incoming travelers off international flights versus the person who answers the phones for Inland Revenue.
The briefing paper sets out that if Ministers have credible evidence that mandating vaccinations for high-risk roles, such as at the border, can impede community transmission of the virus, they can justify it based on the state’s legitimate interest. The justification is not based solely on the health benefits for the vaccinated individual. The requirement can only be justified if it is necessary and cannot be achieved by other means.
Given the lack of data supporting the effectiveness of the Pfizer vaccine at preventing or reducing transmission, as well as the emergence of the Delta variant, it highlights just how delicately balanced the legal justification for the vaccine mandates were when they were introduced later in 2021.
Interestingly, when setting out the benefit-risk assessment in the Clinical Evaluation prepared by Medsafe in January 2021, it noted that “arguably” specific populations within New Zealand should have separate benefit-risk assessments, including the elderly, staff at quarantine facilities and healthcare professionals.
Why then was Medsafe not asked by government to conduct specific benefit-risk assessments, which would take account of updated data on safety, efficacy and transmissibility and new variants, when decisions were made to apply mandates to certain workforces?
Playing Fast and Loose with Risk Benefit
The regulator’s risk-benefit assessment is crucial in any approval process because it is the primary way in which safety is determined. Indeed on the Medsafe website, under the section headed, “How is the safety of a medicine established before it is approved for use in New Zealand?” it states, “Medsafe reviews the risks and benefits for each specific medicine to ensure that the safety profile is acceptable (i.e., the benefits of the medicine outweigh the risks).”
In other words, safety is determined by a positive benefit-risk assessment. It is an assessment that the benefits of the medicine outweigh the risks. As far as the Pfizer vaccine in New Zealand is concerned, however, it has only ever received one benefit-risk assessment by Medsafe and that evaluation was “not clear”.
That has not stopped elected representatives, officials and others from taking a more bullish view on the issue. Individual healthcare professionals and advisory groups can of course form their own views on the vaccine and many, such as the Independent Safety Monitoring Board chaired by Dr John Tait, do hold the view that the benefits of the vaccine outweigh the risks.
But for the purpose of the approval process it is the Medsafe evaluation which is the sole determinant. However throughout the vaccine rollout politicians have disingenuously suggested, either explicitly or implicitly, that Medsafe has determined that the benefits of the vaccine outweigh the risks.
One such example is Minister Grant Robertson who responded to an Official Information Request about the Pfizer vaccine in December 2022. In his response, Minister Robertson stated:
Medsafe provides independent advice to the Government and approves all medicines and vaccines available in New Zealand. Medsafe evaluates applications to ensure that they comply with international standards and local requirements for quality, and that the expected benefits outweigh the risks of harm in the intended treatment population. Only then will Medsafe recommend approval for use in New Zealand.
Medsafe first recommended provisional approval to the Pfizer/BioNTech vaccine for active immunisation to prevent COVID-19 caused by SARS-CoV-2 in February 2021. Through the regulatory approval process, Medsafe concluded that the Pfizer vaccine has been tested and was safe and effective for the vaccine’s use to protect individuals from the virus in New Zealand.
When requested to explain the basis for his statement “that the expected benefits outweigh the risks of harm in the intended treatment population”, Robertson replied that, “This comment was a description of Medsafe’s assessment process”.
Robertson also referred the request to Chris James at Medsafe, who responded that, “Medsafe did not provide any briefings to the Hon Grant Robertson on COVID-19 vaccines”.
Medsafe also confirmed in the same letter that, “A benefit/risk analysis was undertaken by Medsafe prior to the Pfizer COVID-19 vaccine (Comirnaty) being granted provisional consent for use in New Zealand. The assessment has been released in a previous response under the Act and can be found here. Please refer to Document 10 on page 94.” That assessment is as described above – in other words, an assessment that the benefit-risk balance was “not clear”.
The approval of the Pfizer vaccine in New Zealand was undoubtedly a challenging proposition. Medsafe undertook a thorough and rigorous evaluation in consultation with other expert bodies in New Zealand and from overseas.
However, there do appear to be serious questions about how the government then represented Medsafe’s clinical evaluation to the public during the vaccine rollout and how this impacted on informed consent and on the legality of the mandates. In particular, it is clear from the documentation that Medsafe and relevant government Ministers knew from very early in the vaccine rollout that it was questionable whether the vaccine would prevent or limit transmission, and furthermore they were advised that having “credible evidence” of transmission reduction was absolutely crucial in the legal justification of any mandate that required vaccination.
