Efficacy rate alone not enough to determine overall value of a vaccine

Anastasia Tsirtsakis

13/01/2021 5:28:12 PM

Many have highlighted AstraZeneca’s apparent 62% efficacy as a reason for Australia to seek out alternatives, but the candidate has a number of other significant advantages.

Graphic representing vaccine efficacy.
Until Oxford University and AstraZeneca provide the Therapeutic Goods Administration with complete data, the question around herd immunity is difficult to answer.

AstraZeneca released phase 3 results on 8 December. They showed the vaccine is effective at preventing severe COVID-19, with no hospitalisations more than 21 days after first injection, but also only 62% at preventing symptomatic COVID-19 more than 14 days after receiving two full doses.
At the time, questions were raised over the way the overall efficacy rate of 70% was determined, but it was not until yesterday that the Australian and New Zealand Society for Immunology, and the Australasian Virology Society called for an immediate pause to the rollout – a public position both organisations later retracted.
However, these voices were not alone in expressing reservations about the AstraZeneca candidate; Australian Medical Association WA President Dr Andrew Miller, Monash University Infectious Diseases physician Associate Professor Michelle Ananda-Rajah, and the Kirby Institute’s Professor Raina MacIntyre have all called for Australia to prioritise efforts to secure mRNA candidates from Pfzier/BioNtech and Moderna.
Conversely, the Australasian Society for Infectious Diseases, the Australasian College for Infection Prevention and Control, and the Public Health Association of Australia have all come out in support of the AstraZeneca candidate’s role in the Federal Government’s COVID-19 vaccine strategy.
The public debate appeared to catch Professor Paul Kelly by surprise, with Australia’s Chief Medical Officer telling the Today program he is ‘not sure’ why the issue is being raised now.
But according to Professor Adrian Esterman, Chair of Biostatistics and Epidemiology at the University of South Australia, there is a ‘strong argument’ for vaccinating at-risk groups as soon as possible with two doses of the Pfizer/BioNTtech candidate that Australia has already secured, before ‘holding off’ until more doses become available.  
‘If, after the full phase 3 trial results are in, the AstraZeneca efficacy remains close to 60%, then it would not be possible to achieve herd immunity using this vaccine,’ he said.
According to reports, AstraZeneca expects to deliver updated data to the Therapeutic Goods Administration this month.
But until that data comes through, Professor Marc Pellegrini, an infectious disease physician at the Walter and Eliza Hall Institute of Medical Research (WEHI), says the question around herd immunity, while critical, is difficult to answer.
‘It’s not because I don’t have the numbers, it’s that the numbers just don’t exist,’ he told newsGP.
‘We do need to look at the global situation and not just a single number to say that 62% is inferior to 95% – well of course it is, but that’s not the totality. Nor, indeed, does it tell you what the outcome is going to be.’
Dr Abrar Ahmad Chughtai, a lecturer in epidemiology from the School of Population Health at the University of New South Wales, believes the best strategy is to go ahead with the AstraZeneca vaccine. He says, however, the focus will need to turn to higher uptake if trial data reconfirms a lower efficacy rate than other candidates.
‘Although there is limited evidence, some studies show that to control epidemics vaccine efficacy has to be at least 60% when coverage is 100% and at least 80% when coverage drops to 75%,’ he said.
‘So if we use [the] AstraZeneca vaccine a higher coverage will be required, which may be a challenge, but achievable.’
Complicating the issue is the fact that while AstraZeneca’s candidate is unlikely to achieve the same efficacy as other existing candidates, it has proved to stop people from getting severe disease and dying.

Unlike mRNA candidates, the AstraZeneca vaccine can be manufactured in Australia. 
‘The AstraZeneca vaccine is actually more effective than 61% in preventing people from dying, meaning that those that do get infected might have a very mild disease and might actually be shedding less virus,’ Professor Pellegrini said.
‘So although they might actually carry some virus and have some mild symptoms, they might have a lesser capacity to transmit the virus.
‘It’s [also] quite possible that that 39% of people that still do get infected actually have a much lower capacity to transmit virus and therefore it would equate to a degree of transmission blocking, despite the fact that some people still get infected.
‘This is why you will see a difference of opinion – because it’s based on some degree of speculation and assumption.’
When considering which vaccine is the best option, Professor Pellegrini believes it is therefore too simplistic to see efficacy as the sole determinant.
‘Many, many things go into the calculation of which vaccine may or may not be better or effective,’ he said. ‘Only one of those numbers is how efficacious that vaccine is on the present data.
‘The other calculations are, how can we access the vaccine? Can we access enough doses of, say, the Pfizer vaccine to be able to roll it out in a very timely fashion? Would we ever be able to get the Pfizer vaccine distributed to the remote areas in Australia? Because this vaccine needs to be delivered at –70⁰C, which is a logistical nightmare.
‘That has to be overlaid with the fact that we’re dealing with a moving target; the virus is not going to be the same today as it will be in several months’ time. So we have no idea how that will play out into the whole game.’
When it comes to vaccination, Professor Pellegrini says the rationale is twofold – stopping people from developing severe disease and dying and, in the longer term, a level of herd immunity.
‘From my perspective, the immediate imperative is to try and stop people from dying if they become infected, and certainly the AstraZeneca vaccine seems to be able to do that,’ Professor Pellegrini said.
‘I think that both vaccines, honestly, afford protection and may even contribute to a degree of population immunity.’
While efficacy rates differ, what remains consistent is that confidence in the vaccine rollout is vital to ensuring widespread uptake.
Australia’s Chief Medical Officer Paul Kelly told Nine’s Today program on Wednesday he is concerned the debate regarding efficacy could diminish people’s faith.
‘Once controversy is opened up and people make comments based on interim results … of course, people will be [questioning] whether it’s the right decision,’ he said.
‘We’ll be guided by the actual medical advice.’
Speaking at a press conference on Tuesday with Federal Health Minister Greg Hunt, RACGP President Dr Karen Price said the college is ‘working constructively’ with the Government to ensure a confident vaccine rollout.
‘Australia has historically and previously achieved around a 92% immunisation coverage and I see no reason for that to change with this COVID vaccination program,’ she said.
‘GPs are ideally placed all across Australia and our highly trained and trusted members are ready to inform members of the public, go through a consent process, and [make them] ready to vaccinate.
‘Your GP will be able to assist you with that information and help to create an understanding through the available evidence.’
Professor Pellegrini agrees that confidence in the Government’s vaccine roadmap is ‘incredibly important’.
‘I don’t think we could make a big mistake,’ he said. ‘If we pursue one vaccine and we find that another vaccine is better, then we can make every effort to obtain that other vaccine and there’s nothing really lost, apart from money.
‘The biggest mistake would be waiting too long to start initiating a vaccine. It’s important to start considering how we roll out and start getting a vaccine out to understand how many people want to be vaccinated.’
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Dr David John Ritchie   14/01/2021 12:08:53 PM

It is reported that at an early stage of the AstraZeneca, the first dose was a half dose followed by a full dose, and that this proved to be more effective in stimulating antibodies than two full doses. Why is this protocol not being followed? Does anyone know?

Dr Gerald Raymond Segal   14/01/2021 8:42:11 PM

It is clear that it is the Astra Zeneca vaccine is the one we as GP's will be administering. What is not clear is what dosage regime will we be using. Studies show that 2 FULL doses achieve 60%+ benefit but a HALF dose followed 4 weeks later by a FULL dose gives 90%+ efficacy. Can anyone tell me why we are not going with the "best" regime?
Gerald Segal GP