COVID-19 impact as at 31 January 2021

Johns Hopkins COVID-19 Dashboard

As COVID-19 continues its march across the globe with new strains emerging from the United Kingdom, South Africa and now Brazil, the continuing health burden remains critical. With 102.5 million confirmed cases worldwide, 2.2M deaths (of which the United States accounts for 439,000 followed by Brazil with 224,000) the vaccination program combined with public health measures (use of face masks, social distancing, use of hand sanitisers and on-site deep cleaning) remains the best course of action to bring the pandemic under control and ultimately end it.

SARS-CoV-2: effectiveness of the Oxford AstraZeneca vaccine

 

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Of the 58 vaccines under development to combat COVID-19, three vaccines so far have proceeded satisfactorily through the clinical trials process - one of these from the Oxford University - AstraZeneca partnership is scheduled for widespread inoculation of the Australian population during 2021 and onwards. This vaccine has been developed as a non-profit intervention aimed at "global supply, equity, and commitment to low-income and middle -income countries" (www.gavi.org/news) and has an agreement under the COVAX facility. Currently the vaccine is shown to have 70.4% efficacy.

Designated as ChAdOx1 nCoV-19, it utilises a chimpanzee adenovirus to enable a vectored vaccine. 

The four randomised controlled clinical trials of this vaccine took place in the UK, South Africa and Brazil with the UK and Brazil components being the first to report with interim efficacy results. Of note from these studies:

• 11, 636 participants were in the clinical trials
• 87.8% were aged 18-55 years
• 82.7% were white
• 60.5% were female

The phase 1 stage of the trial had supported a two dose regimen administered 28 days apart. There were no hospital admissions for those who received the vaccine whereas ten admissions occured in the control groups. An interesting development for the Oxford-AstraZeneca trial was the accidental provision of a low dose of the vaccine for some participants in the UK which was then boosted by a standard dose 28 days later that appears to have not reduced the level of effectiveness.

The clinical trials for this vaccine had substantial strengths including -

• a large sample size
• randomisation to vaccine groups
• inclusion of diverse sites with different races and ethnicities
• standardisation of key elements between trials
• balance of participant characteristics between the vaccine groups 
• similar results in Brazil and the UK for those receiving the standard dose regime providing credibility.

There have been limitations for the clinical trial studies as well such as -

• less than 4% of participants were older than 70 years of age
• no participants older than 55 years received the mixed dose regime
• unavailable results as yet on those participants with comorbidities and any impact.

The two dose regime poses its own challenges for health systems to coordinate and manage. A substantial practical advantage of the the Oxford AstraZeneca vaccine is that it can be transported and stored through the routine refrigerated cold chain whereas in contrast the Pfizer vaccine requires ultra-low temperature freezers.

[Information for this post has been drawn from The Lancet December 8, 2020]

A link is provided below.

Oxford- AstraZeneca vaccine - The Lancet

Artificial Intelligence - AI - the jury is still out

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'Artificial intelligence' or AI. The terminology evokes images from film and television such as The Terminator film franchise which has the fictional 'Skynet' computer system become self aware and decide to wipe out the human race or the computer HAL from Stanley Kubrick's 2001 - A Space Odyssey which attempts to eliminate the astronauts on board their spacecraft. Or more laterally the androids from Star Wars, Star Trek or the Alien film franchise. 

For most people exposure to some form of AI already occurs with robo systems which do debt recovery, conduct surveys or provide basic insurance quotes. But what is AI exactly ?

The definition of AI can be applied to any method, process or technique that enables computers to mimic human intelligence. This is achieved with decision trees, logic algorithms, if-then rules and machine learning. Machine learning (or ML) itself operates with a core capability described as a neural nets which are created by programmers  using a learning algorithm supported by terabytes of data to train it. Computers therefore become able to train themselves with recognition of specific words or phrases or images.  How is AI applied at present ?

AI is used for multiple forms of modelling and then decision-making recommendations (predictive, detection-based, prescriptive), computer visuals (such as for facial recognition, image analysis, sensors) autonomous machines (drones, large vehicles in controlled environment, robotic assembly lines) and conversational platforms (virtual assistants, translations, inquiry assistance). 

There are however significant risks with the development of AI and unrestricted use. The late physicist, Stephen Hawking saw AI as a direct threat to the human race if not controlled and a range of AI-related failures already have been experienced by Amazon, Microsoft and the US justice system. The Loomis case in  the US state of Wisconsin in 2013 being a key example. In the Loomis case, AI was used to determine the length of sentence which the offender, Eric Loomis, should serve for car theft. The AI technology known as the Compas Program, gave a sentence at the higher end of penalty and more than would have been expected for the crime involved. This case remains controversial.

The Australian Institute of Company Directors (AICD) have warned that "AI and ML designed intelligently and deployed sensitively herald immense opportunity. But the technology is not without risk. Flawed algorithms and biased data sets can lead to unintended outcomes while increased automation will likely reduce the needs for employees engaged in repetitive work" (June 2019).

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Clinical trials - the four phase process

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Much of the focus on managing and ultimately containing COVID-19 has naturally centred on the successful development of vaccines to protect people from the onset of infection. 2020 has seen an extraordinary race in the biomedical and pharmaceutical industries to find suitable candidates which can be deployed for public health programmes. Central to this process is the time taken to test drug for efficacy and safety - for the COVID vaccines, a process which normally proceeds over  years has taken only months.

Prior to proceeding to a clinical trial, compounds which constitute the drug are screened at a laboratory setting using computer modelling, tissue samples and pathology to assess which are likely to function with humans. The compounds are tested in at least two species of animals to establish performance, how they are metabolised and any side effects. After this preliminary stage, a candidate drug typically proceeds through a four stage process -

Phase 1: After approval from a human clinical trial ethics committee, and the appropriate health authority (Food and Drug Administration or FDA in the US, and the Therapeutic Goods Administration or TGA in Australia), the drug candidates which are the most promising are tested in small groups of healthy volunteers, usually young to lower middle age, non-smoking and normal body weight. For Phase 1 trials targetting life threatening diseases such as cancer, terminally ill patients as test drug recipients are included. Only one in five Phase-1 tested drugs are successful and proceed to being available for use.

Phase 2: The candidate drug is tested on a larger group of people with an illness to evaluate whether it works and to confirm safety, tolerance for patients and dosage requirements.

Phase 3: The trial is expanded for testing with hundreds or thousands of patients often in multi-institutions in various countries in what is termed a 'randomised controlled trial'. Some patients receive placebos (such as harmless sugar pill) while others receive the test drug itself. Neither doctors nor patients know whether they are using the placebo or the drug which enables an unbiased analysis of the response to the treatment and any side effects. This stage also enables measurement of how effectively the drug works in comparison to existing therapies, the economics of treatment and in quality-of-life terms.

Phase 4: Drug receives regulatory approval and is included in routine clinical practice. Ongoing surveillance studies may reveal any rare side effects or extra benefits.

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