1 Thread on Astra Zeneca vaccine

Irrespective of your political views you hold, Australians should be disappointed about the misleading headlines around the Astra Zeneca vaccine in the SMH and Age today including unhelpful statements made by some in the medical profession

2 The primary and immediate focus of our public health strategy is prevention of severe disease from symptomatic infection with SARS-CoV-2. The efficacy estimates reported in the trials have been generated at a certain time point in the early stages of follow up of these trials

3 Data collection remains ongoing and focusing just on results to date can lead to erroneous conclusions on comparative effectiveness on vaccines. Evaluation of efficacy does not cease once early results of phase 3 trials are reported

4 Those who participated in the trials will be followed up to determine whether early estimates of efficacy shift overtime. Further governments have real time surveillance systems in place to monitor effectiveness once it is rolled out to the broader population

5 Of the preliminary results on efficacy published to date both the Astra Zeneca and Pfizer vaccine have been demonstrated to be effective at preventing severe disease from symptomatic infection

6 Of those participants in the Astra Zeneca trial who were allocated to receive the vaccine & who were subsequently diagnosed with COVID-19, none were hospitalised or experienced severe symptomatic infection (only those in the control arm). At worst only milder symptoms occurred

7 This is not dissimilar to what we see in those who still get the flu despite receiving their flu shot. Flu vaccination has been shown in several studies to reduce severity of illness in people who get vaccinated but who still get symptoms. This concept also applies here

8 The immediate focus on herd immunity is misleading as this is a longer term aspiration. In the event there was community transmission the first priority is to reduce the burden on our health care system and people getting severely ill and possibly dying of the illness.

9 Based on published data to date both the AZ and Pfizer vaccine achieve that goal of reducing burden of disease. However based on the same preliminary phase 3 data there remains paucity of data as to whether either vaccine significantly prevent asymptomatic infection

10. There is an early signal in the data within a small sub group of participants that the vaccines may potentially reduce asymptomatic infection and thus transmission of disease but more robust data needs to be generated over the coming months to definitely answer this question

11. In other words neither the Pfizer or Astra Zeneca vaccine nor any other vaccines for that matter have so far conclusively demonstrated they prevent asymptomatic infection and transmission which is also critical to achieve herd immunity

12. I think it is erroneous to conclude at this point in time that the AZ vaccine is not efficacious enough to achieve herd immunity as we don’t know the answer to this question for any of the vaccines. But the AZ vaccine appears so far to be effective at reducing severe disease

13 Also for the other vaccines we only have short term follow up on efficacy against symptomatic infection. We don’t the durability of the initial efficacy estimate for all the vaccines and whether a third dose is needed for all of them a year down the track

14 Most importantly based on the data published to date on both the AZ and Pfizer vaccine they are both appear to be effective at preventing hospitalization even if there is breakthrough symptomatic infection

15. I am disappointed by some in the medical profession who have prematurely dismissed the AZ vaccine. It is important that information on vaccines is heavily scrutinized given the public interest but it must be done within context of how the data has been generated.

16 There are strengths and limitations with the published data generated for both vaccines as well as residual uncertainty on durability as well as the transmission question. This is not solely limited to the AZ vaccine

17. I remain passionate on a range of issues associated with the COVID19 pandemic and response but on the vaccine question I need to call the facts as I see it

18. Main message is to look at the subtlety of the data that is driving the headline efficacy figures for both vaccines. It is hypothetically possible that immunity could taper overtime unevenly across different vaccines with convergence of efficacy in medium to longer term

19 also trials are not 100% comparable at this point as Astra Zeneca only had about 10% of its data generated in those > 55 years while with Pfizer it was 40% +. Subtle differences in protocol and demographics need to be taken into consideration when comparing trials

20. Full text of both published trials below noting fuller dataset will be assessed by regulator

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext

https://www.nejm.org/doi/pdf/10.1056/NEJMoa2034577

21. I have tried to not get into too much technical detail and I haven’t discuss safety as this not in question for either vaccine. As with any vaccine there are rare side effects but for a vast majority of participants they are well tolerated and benefits far outweigh any risk.

22. Safety will also be continuously monitored by the TGA during rollout

Overall we are spoilt for choice in Australia. To paraphrase Ed Rooney from Ferris Bueller’s Day Off:

“Between [vaccine] and nothing... I'll take [vaccine]”

23. Correction to earlier. The results of the asymptomatic infection (AI) analysis for the AZ vaccine had very wide confidence intervals (not small subgroup) and even though it suggested if you start with a low dose it reduces AI more than standard dose, this isn’t conclusive

24. Potential issues with misclassification as well as they bundled the analysis on asymptomatic infection with “symptoms unknown” some of which may well have had mild symptoms

25. It is critical for public confidence of the vaccines that the media look properly at the facts before rushing out with a misleading headline.

Too soon to know whether variants of concern will reduce the efficacy of the vaccines but this remains a potential risk to rollout