Dear Bellingen Shire
2 March 2021
A slightly briefer note tonight, as I have had to attend a bunch of meetings. Alas, from the perspective of my poor old dad, who was a golf devotee, doctors do not stereotypically spend every free hour out playing golf. At least, none I actually know. We spend too many spare hours at meetings.
But any way, we all choose our own little purgatories!
We have not a lot of helpful news this week. During the week a suspicion started to arise that the promise of rapid delivery of Covid19 vaccines was going to fall short in number and pace. (Not in efficacy and safety). Just because there are 7.8 billion other people in the world competing for the few hundred million doses currently available, who would have thought that an excuse?! It’s a pretty savage game of musical chairs out there.
The news blitz event of an incorrect dose of a vaccine being given in Brisbane ….? Some things, like black holes and the American electoral system, I just can’t explain. Actually, I could be comfortable with black holes.
We had dinner last week with an old friend who offered a horrible story of their young relative – late 20s -who got Covid19 in the early days, in March last year. A promising lawyer – still sick and still can’t work. This young person has suffered a career arrest as a consequence of the virus, and is an example to younger cohorts that we are not mounting a massive public health response just to protect a few very old folk who no longer pay taxes. We are trying to rein in a nasty disease that we will all eventually be exposed to, which will kill some of us, and which will also destroy the lives of too many younger folk.
I found the seminal article in the New England Journal of Medicine in November that reported the phase 3 trials of the Pfizer Covid19 vaccine. They tested 44820 people in about 150 different sites around the world. Many were Caucasian but ethnic minorities were included, Median age was 52 and 21% had at least 1 other chronic health condition. i,e. it was a wide cross section of age , gender, ethnicity and health status. Half got the placebo – that is no active ingredient. 6 people died during the trial – 2 in the real vaccine group, and ironically 4 in the placebo group. They had cardiovascular events – nothing to do with the vaccines. So you can see how easy it is for someone to grab a number and completely misinterpret it.
They reported divergence of infection rates after only 12 days. That is – it was apparent after only 12 days that the number of new infections acquired in the placebo group was outstripping the number in the vaccinated group. This is partly why the American Food and Drug Administration felt safe to make emergency approval in the face of the catastrophe unfolding in their country. It is also evidence that our TGA has included in its approval. However, our authority has had the luxury to see effectively the roll out of a stage 4 trial and reserve its approval till ready.
Some folk are a bit confused about the nature of clinical trials for a medicine or vaccine (or surgical procedure, instrument, implant etc). It can be daunting to be shown exclusion lists from phase 1 trials and easy to assume there is something being hidden, when you don’t have the luxury of medical and research training. So lets speak at how health research develops.
Firstly there is a huge body of basic research into physiology (how our bodies work), the nature of diseases both known and predicted, ideas or theoretical proposals as to what can be done. Then there is lab research into developing substances or tools and observing what those substances do in cell cultures, and under various conditions, and yes, though many don’t like it, in animal models. These are often mice bred to have a condition very similar to the human disease.
Eventually candidates of treatments or chemicals emerge and are cross-referenced in different labs to try to ensure the effect wasn’t just a fluke or random chance. This stuff is what fills most scientific journals, takes years or decades, and requires scientists to beg or plead for, or pursue competitive funding. The development of mRNA vaccines had been going on well before Covid19.
So then phase 1 trials are mounted in small groups of healthy human volunteers to work out if the chemical is safe, what is an effective dose, how is it given, are there any marked unwanted effects. The Sputnik trial only got to this stage in mid last year when the Russian president announced it was going out to full use! Hence my outrage in these letters at that dangerous premature announcement.
Phase 2 trials deliver the substance to a larger group (in the hundreds or thousands), to see if it actually works and if there are any broader safety issues. There is usually a range of people excluded from phase 1 and 2 trials – until researchers have a sense of safety of the new substance.
Phase 3 trials involve mostly 10s of thousands of subjects in multiple centers – often all around the world – to look at the effects in a broader cross section of people and conditions to check for efficacy and safety. This is what was reported before Christmas for the covid19 vaccine, and made the world jump.
Phase 4 is effectively a monitoring program after the substance has gone to market – ie approved for the general public. Yes, occasionally some treatments are found to be not ok in the real world, despite going through the process, and regulators are constantly looking to improve surveillance – at least here and in countries not run by uneducated populists. The covid19 vaccines will be the most intently monitored medicine in decades.
But the process usually takes 10 -15 years. How do we square off these vaccines coming onto market in 1 year? Well partly, mostly, masses of money, focussed intellectual muscle, and government commitments. The research world is full of scientist complaining they are spending more of their energy chasing funding than actually getting into their dirty white coats and hovering over smelly little pots. But then came Covid! What a year to be a researcher.
I understand most of the basic research was already done re the concept of mRNA vaccines – which could easily be 1-2/3 of the whole time line. I did mention in a previous letter that the health community has been talking about this kind of pandemic coming as long as I have been associated with health care – since 1979 – and particularly this kind of coronavirus, or similar, since the first SARS nearly 20 years ago.
So here we are with a rapidly developed, though chemically relatively simple vaccine ready to be used in Australia, rolling just a bit slower than the pollies expected. But again, we have been spared the urgency of other places.
So, here we are still at about the same risk as we were 11 months ago, except at least we know the enemy. While we wait for the cavalry to arrive we could still have a break out any day.
So, here, our doctors, nurses and admin staff are resolving to keep our local testing clinic going, as it is, 9-9.30 at Watson St. in Bellingen.
I believe almost all your local GP practices have been approved to administer the phase 1b (Astra Zeneca vaccine), but we still don’t have the precise detail of when, and how many per day, and how the process will work. Might not be before the end of this month. We will let you know.
Whoops! So much for brief. And not even a single musical reference!
Please check all and any detail with your own clever GP, before they have a syringe in hand, and ask them all your questions in advance! Because this is just one of 7 billion perspectives.
Dr Trevor Cheney