‘Mixing and matching’
Is the UK confounding the experts?
4th January 2021:
For the second time within a month, the UK has been criticised by US scientists over their handling of vaccines against the Covid-19 virus. In early December, it was rebuke at the speed with which the Pfizer-BioNTech vaccine had been approved by the UK Medicines Regulatory Authority (MHRA) – although an unconvincing apology ensued the following day. On New Year’s Day, the New York Times1featured an article in which several US scientists were openly opposed to decisions made by the UK government’s advisory body, the Joint Committee on Vaccines and Immunisation (JCVI) to delay second (booster) doses, immunise more people and allow different vaccines to be used for the first and second (booster) dose.
It all comes at a time of crisis due to uncontrolled spread of the Covid-19 virus in the UK. This weekend saw the highest daily number of new cases since the beginning of the epidemic. The recent surge in cases is a multifactorial phenomenon but – as I described a few days ago – a major factor is that a more contagious variant of the virus is circulating throughout the British Isles. At least in the short to medium term, immunisation is the only public health intervention that can substantially lessen the impact of this epidemic. Neither ‘testing and tracing’ or closing-down the country’s activities in the middle of winter – with all its detrimental consequences – have been able to stem the surge of new cases2. It’s therefore critical to deploy vaccines as efficiently as possible.
Graph showing daily cases in UK2
There are scientific reasons why it makes sense to adjust recommendations on key issues – such as booster doses, the mixing and matching of different vaccines – according to changed circumstances. There are hardly valid grounds to support the allegation of US public health experts that: ‘………the British have abandoned science completely now and are just trying to guess their way out of a mess’. Indeed, I would argue that the opposite is the case. The Joint Committee on Vaccines and Immunisation (JCVI) has used scientific analysis to resolve how best to implement the existing available vaccines to deliver the optimal outcome. Which brings us to a central question. How to judge what is best for the health of the nation? There is nothing new in this question, although Covid-19 has brought a compelling resonance to it. The answer is somewhat prosaic. The UK has a National Health Service and, given limited resources, a central mantra of its operation is based on cost-effectiveness. In stark terms, the economic evaluation of the costs and effects of different health interventions. It is measured in health outcomes; for example, what is the cost of preventing a death or a hospital admission from Covid-19 and, given a set of alternatives, which gives the best outcome for the money invested?
Given this rationale, the JCVI is adhering to the principles of their parent advisory body, the National Institute of Clinical Excellence (NICE) that, over decades, has served our National Health Service well. Recommendations on medical interventions are advisory, not executive, but we abandon them at our peril. This is not to deny that there are pros and cons to the two major JCVI recommendations: (1) delaying (not cancelling) the second or booster vaccine jabs; (2) allowing different vaccines to be used for the first and second (booster) dose.
There are counter arguments to delaying the second booster dose (close to a million persons have currently received the Pfizer-BioNTech vaccine). It is logistically complicated because this change must be communicated by the heath professional responsible for giving the immunisations. It will be time-consuming and demanding of resources. Many of those who expected to be recalled have already made arrangements that must now be cancelled. Ethically, it can be argued that they have been denied a vaccine to which they are entitled (these were the terms under which they agreed to be immunised). Finally, protection afforded by two doses is better than just one. The debate is whether these arguments outweigh the JCVI recommendations to protect more people thereby potentially reducing hospital admissions, deaths and disabilities (including long Covid). It is also likely (but not certain) that reduction of person to person spread of the virus will be decreased in proportion to the number of persons immunised. There is a biological rationale to giving a booster with a commercially different vaccine in the exceptional circumstance that further doses of the original vaccine are not available or there is no record of which vaccine was given as the primary immunisation. Both stimulate an immune response to the Covid-19 spike protein, but no trials have been performed to test the validity of reciprocity (‘mixing and matching’) of vaccines from different manufacturers.
I think the JCVI has made a correct and courageous decision. It’s the responsibility of scientists to use existing data (while recognising the shortcomings) to assess what we know and to recommend action that has the best public health outcome. There is not likely to be a one-size fits all directive (anyway, it is for governments to formulate policy), so discrepancies on global recommendations and policy may be divergent depending on temporal and geographical variables.
To summarise: immunising more people is undeniably cost-effective. Delaying (not cancelling) the booster has only a marginal downside. Giving a different vaccine to that used for the first dose, providing it is based on inducing a response to the ‘spike protein’, may be beneficial, but we do not know this. In what are expected to be exceptional circumstances, it is important that there is formal evaluation of outcome in all instances of ‘mixing and matching’ (including adverse events). Individual heath providers have discretion as to whether or not to they follow the JCVI’s recommendation.
If we have learned anything from this pandemic, it’s that the best science does not deliver certainties. Absolutes or statements that include words such as ‘never’ are anathema to the modus operandi of science. Debate, rigorous argument and diversity of scientific disciplines forge a pathway that progresses knowledge. Science increases our probability of making good decisions. In contrast, ‘ex cathedra’ statements from the US Chief Scientific Adviser and other US scientists are neither wise, nor helpful. It might be added that the US does not have a National Health Service. Delivery of medical care is inequitable, biased to benefit those who are wealthy, rather than those in need.
- www.https://coronavirus.data.gov.uk/ (04/01/2020)
Copyright Richard Moxon 03.01.2021
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