The risk-benefit argument

The RISK-BENEFIT argument

Below is an excerpt of longer form research, which can be found here.

Introduction:

On the 10^th July 2021, a risk-benefit analysis for people aged under 60 in Australia investigated TTS following AstraZeneca: “For the current situation of low incidence of COVID-19, the risk of fatality from possible TTS or serious morbidity such as stroke in healthy younger adults, is unacceptable in Australia, when there is a choice of other vaccines.”[1] Messaging and risk assessment by the government and media failed to transparently communicate the known higher risk at the time of more severe TTS from AZ for younger women. What is informed consent without access to knowledge?

[1]https://doi.org/10.1016/j.vaccine.2021.07.013

Throughout 2021, the government presented a risk-benefit argument with more certainty than the evidence indicated. Australia’s risk-benefit model referred to by government for AstraZeneca in Australia for all ages is published in the document ‘Weighing up the potential benefits against risk of harm from COVID-19 Vaccine AstraZeneca.’[1] There are several significant issues with this document.

‘‘Weighing up the potential benefits against risk of harm from COVID-19 Vaccine AstraZeneca’[2] is authored to enable interpretation of risk-benefit assessment to curtain vaccine supply issues, and failures to choose and procure vaccine options for Australians.

28^th June 2021, under the heading ‘Estimating harm from TTS’: “While the estimates of risk in Australia are similar to overseas estimates, they are less certain for people aged under 50 years. This is because people in this age group are no longer vaccinated with COVID-19 Vaccine AstraZeneca in Australia.”[3] [Prime Minister Scott Morrison had just announced the same day this document was published that AstraZeneca would be used (and is the only vaccine available) for those aged under 50].

In the document, risk-benefit analysis was based on ATAGI looking at “three scenarios that show the benefits and risks of vaccination with COVID-19 Vaccine AstraZeneca.”[4] However, risk estimates based on data as of 16 June 2021 are incongruent and self-disclosed as “uncertain” as the ‘cases of TTS due to COVID-19 Vaccine AstraZeneca’ are “based on small numbers of vaccinations in people under 50 in Australia.” [5] Estimates do not reflect the increased risk of TTS that occurs with an increase in vaccinations, which at this point [June 2021], is already seen in larger vaccine rollouts in countries such as the UK. Whereas the ‘hospitalisations, ICU and Deaths prevented’ columns seen as ‘potential benefits’ of the AZ vaccine are calculated from confirmed data in Europe and reflect an increase in infection rate similar to varying outbreak scenarios classified as from ‘Australia’ (low), ‘Victoria’ (medium) and ‘Europe in January 2021’ (high).

In the government and media, international data was quoted as it related to COVID-19 the virus, whenever it was convenient to alert the public to increase vaccine uptake, but international experience was not quoted accurately when it came to risks of TTS from the AstraZeneca COVID-19 vaccine. If the risk assessment had drawn on existing data from actual events internationally and been comparing ‘apples with apples’ in conveying risk scenarios, the very foundation of risk-benefit in Australia would have been more accurately communicated. Why, with access to international evidence, is that evidence not referred to in comparing the number of vaccines administered in said country, to the covid-19 infection rate in said country? In an evolving situation where a vaccine is globally rolled out to millions (after a mere 12,021 first doses were administered to people aged over 18 in clinical trials), why not look at locations where the most doses have been administered for indication of risks?

Australia’s data estimates in the government document ‘‘Weighing up the potential benefits against risk of harm from COVID-19 Vaccine AstraZeneca’[6] also do not differentiate the risk of TTS based on first and second doses of AstraZeneca, where there is a significantly much higher risk of TTS from the first dose. It is only in September 2021 that the Australian government Department of Health publishes ‘COVID-19 vaccination – vaccination data’ as excel datasets available to view for the general public and the datasets do not differentiate between the types of vaccine, or first and second doses of each type of vaccine, they just use the word ‘vaccine’.[7]

This is a problem with this interpretation of the data. First and second doses of AstraZeneca are combined to assess risk of TTS. However, because the risk of TTS is much lower from a second dose, the results are skewed so it appears the risk of TTS is significantly lower than it would be if the data displayed the risk of TTS from first doses only.

If the TGA released data of how many first doses of AstraZeneca in Australia, and how many TTS cases and fatalities occurred from first doses, we would have an accurate picture of risk assessment for Australia. Globally, as of 14^th January 2022, the European Medicines Association (EMA) states that: “[…]out of 1,809 thromboembolic events with thrombocytopenia reported worldwide, 1,643 were reported after the first dose and 166 after the second dose.”[8] It is unknown to us how many first doses of AZ have been administered in the approximate 183 countries where it is supplied worldwide. If we did have this figure, then an approximate global risk of TTS could be surmised. Combining the first and second dose data obscures the risks from the Astrazeneca vaccine associated with the first dose.

Published in January 2022, employees of AstraZeneca publish a study funded by AstraZeneca on ‘Geographical distribution of TTS cases following AZD1222 (ChAd)x1 nCoV-19) vaccination.’ [9] It is the closest study we have been able to locate which compares TTS cases from across the globe, which shows that AstraZeneca the company does hold that data in their global safety database but (for whatever reason) are not going so far as to communicate what proportion of doses are first or second. This is a significant factor in being able to accurately read the risk of TTS from first doses where the risk is much higher, and subsequently an accurate risk from second doses [and third, and fourth…]. If the doses are bundled together as we see in this study, the risk is not accurately displayed. Also, the study has limited the definition of TTS cases to occurring within 21 days of vaccination from AZ, whereas other definitions suggest it can occur within 28 and 30[10] days. The question then is, why is the company AstraZeneca not sharing data of first and second doses globally?

Official weekly updates in Australia by the TGA state that reports of side effects “are generally consistent with what is being observed internationally,”[11] if the estimates of ‘potential risks’ based on data as at 16 June 2021[12] were actually similar to overseas estimates, they would be reflective of that fact that as an e.g. in the UK alone, there had been 68 deaths from 389 reported cases of blood clots with low platelet levels in people who had the AstraZeneca vaccine up to 16^th June 2021.[13] Below, a study models “the benefits and risks of Vaxzevria distribution from May – September 2021 in metropolitan France, considering French hospitalisation data and European data on TTS.”[14]

On the 1^st July 2021, Eurosurveillance, Europe’s journal on infectious disease surveillance, epidemiology, prevention and control, publishes the study:‘Benefits and risks associated with different uses of the COVID-19 vaccine Vaxzevria: a modelling study, France, May to September 2021’. “When Vaxzevria was used in younger age groups, the benefit–risk balance was no longer as favourable and even reversed in the younger age groups. For instance, using Vaxzevria in the entire adult population would avert four (95% PI: 2–7) COVID-19 deaths in the 18–29 year-olds and six (95% PI: 3–8) in the 30–39 year-olds, but it would be associated with 12 (95% PI: 7–19) and nine (95% PI: 6–14) deaths from TTS in these age groups, respectively.”[15]

With a global pandemic, and a globally administrated vaccine where 12,021 people [aged over 18] received one dose and the rest of the data evolves in real-time in an international rollout, data and information on risks needs to be global, internationally collated, as well as locally.

If there was international collaboration in the form of an independent global safety database for vaccines where health professionals and the public can upload adverse reactions with the results displayed in real-time, and collaboration between medical experts and health researchers amongst countries in the interests of protecting patients from harm, then people would have the knowledge to become informed about their health choices and as a collective we really would be putting safety first.

On 7^th December 2021, Dr Joshua E. Porterfield, PhD writes article for John Hopkins University Coronavirus Resource Center – ‘Why Aren’t We Talking To Each Other About Data?’:

“Data collection from this pandemic has been far from ideal. […] People from different disciplines need to come together to talk about what kinds of data we would like to have prior to the next pandemic — and then put the infrastructure in place to collect them. […] There has been a great deal of frustration in the public and that’s our fault. […] We have to come together if we are going to handle this better in the future.”[16]

As at March 2022, Australian government funded ‘Vaccine Safety Surveillance’ websites such as ‘AusVax Safety’ – ‘Australia’s active vaccine safety system’ (last update March 2022) ‘AstraZeneca COVID-19 vaccine safety data states: “There have been no reports of thrombosis thrombocytopenia syndrome (TTS) following COVID-19 vaccination reported to AusVaxSafety. For more information on all vaccine safety monitoring in Australia and on TTS, see weekly TGA safety updates.”[17] As we know, there have been eleven fatalities in Australia as a result of AstraZeneca. And currently as at March 2022, NSW Department of Health’s ‘COVID-19 Critical Intelligence Unit, Living Evidence – COVID-19 vaccines’ still does not include two tragic deaths caused by Guillan-Barre Syndrome [reported as a result of the AstraZeneca vaccine.[18] Neither of these government vaccine surveillance websites have a breakdown of risk of fatality and adverse reactions from first and second doses.

“Global collaboration and detailed spontaneous reporting are essential to understand and minimise the risk of very rare adverse events, including TTS.”[19]

– Katie Lees’ Family

[1] https://www.health.gov.au/sites/default/files/documents/2021/06/covid-19-vaccination-weighing-up-the-potential-benefits-against-risk-of-harm-from-covid-19-vaccine-astrazeneca_2.pdf

[2] https://www.health.gov.au/sites/default/files/documents/2021/06/covid-19-vaccination-weighing-up-the-potential-benefits-against-risk-of-harm-from-covid-19-vaccine-astrazeneca_2.pdf

[3] https://www.health.gov.au/sites/default/files/documents/2021/06/covid-19-vaccination-weighing-up-the-potential-benefits-against-risk-of-harm-from-covid-19-vaccine-astrazeneca_2.pdf

[4] https://www.health.gov.au/sites/default/files/documents/2021/06/covid-19-vaccination-weighing-up-the-potential-benefits-against-risk-of-harm-from-covid-19-vaccine-astrazeneca_2.pdf

[5] https://www.health.gov.au/sites/default/files/documents/2021/06/covid-19-vaccination-weighing-up-the-potential-benefits-against-risk-of-harm-from-covid-19-vaccine-astrazeneca_2.pdf

[6] https://www.health.gov.au/sites/default/files/documents/2021/06/covid-19-vaccination-weighing-up-the-potential-benefits-against-risk-of-harm-from-covid-19-vaccine-astrazeneca_2.pdf

[7] https://www.health.gov.au/resources/collections/covid-19-vaccination-vaccination-data#september-2021

[8] https://www.ema.europa.eu/en/news/meeting-highlights-pharmacovigilance-risk-assessment-committee-prac-10-13-january-2022

[9] Source is authored and funded by AstraZeneca [accessed 6 Feb 2022]: https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(21)00545-3/fulltext

[10] https://www.tga.gov.au/periodic/covid-19-vaccine-weekly-safety-report-17-06-2021

[11] https://www.tga.gov.au/periodic/covid-19-vaccine-weekly-safety-report-01-07-2021