While the Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency have both approved the Oxford-AstraZeneca vaccine for all adults, Germany, France and six other European nations have recommended it only for those under 65, Belgium and Italy for people under 55 and Switzerland for nobody at all. Why are different regulators making different decisions?
The problem is the relevant trials recruited only 660 subjects aged 65 or over: 6% of participants. It is inevitable some groups are under-represented in studies; the Pfizer trials included only 4% with Asian ethnicity; nobody over 89 took part. But to have so few from those at highest risk from Covid-19 is unfortunate, to put it mildly.
Only two cases in this age range developed Covid-19: one among vaccinated subjects, the other in the group who had the dummy injection. We cannot estimate efficacy from this data alone. Many regulatory agencies concluded there was insufficient evidence on older people, but they certainly did not suggest the vaccine was “quasi-ineffective”, as President Emmanuel Macronthe French president asserted. It is vital to distinguish between absence of evidence and evidence of absence.
In contrast to saying there is no evidence for protection, the MHRA stated: “There is nothing to suggest lack of protection.” Scientific knowledge and indirect evidence lie behind this. First, other approved Covid-19 vaccines do not show efficacy dropping with age. Although AstraZeneca is a viral vector vaccine, rather than mRNA. Second, rather than repeating whole trials on groups who did not take part in clinical trials, say of different ethnicities, researchers use “bridging studies” that compare biological responses. For the AstraZeneca vaccine, there were similar levels of neutralising antibodies across age. It is reasonable to assume protection in older people will be like that in younger adults.
These are not normal circumstances, so the calculus of caution changes. There are nearly 2,500 reported Covid-19 daily deaths across the European countries that have restricted the vaccine. Direct evidence on older people will be coming from a US study, which could change future decisions. But in the meantime, unless there are ample alternatives, regulatory choices may delay protecting the most vulnerable and so cost lives.
• David Spiegelhalter is chair of the Winton Centre for Risk and Evidence Communication at Cambridge. Anthony Masters is statistical ambassador for the Royal Statistical Society