Quick tweetorial on why the design of the different vaccine studies is important. I'm also going to talk about how reporting has coloured the debate.
My disclosures- Minor investigator on ChAdOx trial. No funding to declare. 1/n
My disclosures- Minor investigator on ChAdOx trial. No funding to declare. 1/n
First thing is funding/ sponsorship (who is responsible for trial). Most western vaccines are commercially sponsored and funded though with variable govt involvement. Exception was ChAdOx which was sponsored by Oxford Uni (with some trials yet to report further from AZ) 2/n
Why is this important? Because you may want to know how independent the studies are. E.g. Some concern about Russian Sputnik because it clearly isn't. Some people don't trust drugs companies so those ones may come under different scrutiny. 3/n
No perfect design here as different people have problems with different sponsor models. I like to think ChAdOx pretty independent but funding from NIHR which though not govt direct is still a govt research structure. 4/n
This impacts on trial design (for example much less money in investigator-led than commercial so these trials are set up differently). I co-chair the vaccine research committee in Cambridge and the difference in commercial funded trials is clear. 5/n
An example of how this impacts. ChAdOx recruited in the UK in <20 sites. Pfizer ~100 globally. Much investigator-led trials done gratis (no cash e.g. for the punishing hours I put in personally- reader no sympathy, took it on partly as investigator-led so knew the deal). 6/n
Another example is- you can set your trial up without lonly commercial goals. Here is Pascal Soriot from AZ talking about this. "You have to think that the program we have today was run by Oxford, it was the Oxford program.... 7/n repubblica.it/cronaca/2021/0…
"... and Oxford is an academy group. They´re very ethical, and very academic. So they didn´t want to vaccinate older people until they had accumulated a lot of safety data in the 18 to 55". You can tell from his tone what he thinks of this (he would have done it differently!) 8/n
Next- Endpoints
We are mostly looking at mild symptomatic disease. This is just practical. Hospitalised cases means many more subjects needed. Asymptomatic cases really hard to screen for. Again ChAdOx differs here (will come back to this) 9/n
We are mostly looking at mild symptomatic disease. This is just practical. Hospitalised cases means many more subjects needed. Asymptomatic cases really hard to screen for. Again ChAdOx differs here (will come back to this) 9/n
Endpoint definitions of "disease" slightly differ in the trials so we are not comparing like with like. Have a look at the list of symptoms that get called "symptomatic" and they slightly differ. A sore throat gets called positive in Pfizer (FDA driven) but not in another. 10/n
This leads to the reporting process for participant events. Some are online, some are phone. Differences matter. We recruited in educated HCWs. You would be amazed how many didn't tell us about their fevers and cough until after a positive test! 11/n
However because we were screening them weekly our pick-up was pretty stellar. The screening in ChAdOx is important because it tells us that we are not just converting symptomatic to asymptomatic (or there would have been more in ChAdOx arm) 12/n
But at the same time people are still asymptomatically carrying virus so advice to not change behaviour really is important. Next is populations... 13/n
Lots of things to cover. Ethnicity, age, comorbid conditions etc. Differences in the starting populations may not in the end matter but we might not really know until after roll-out. Lots of work still to be done to understand this. 14/n
The performance of the mRNA vaccines is astonishing but remember the goal is not 100% perfection and having 5 vaccines now working, all of them at decent levels, we need to stop thinking of them comparatively and start figuring out how they fit together in the jigsaw. 15/n
They all have different merits and frankly this is just round 1 so whatever we can do to boost international capacity and co-operation will help for when we have new variants to protect against 16/n
Which brings me to reporting. At the moment there is some terrible nationalism and protectionism happening with vaccines as the punchbag. We need to resist this. Generally all sides behaving badly and media amplify this. 17/n
We need to demand better of them. We have a whole world to vaccinate. We can't let petty politics and dodgy comms get in the way.
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