Lowe on Vaccination Trial Read-Outs

Writing at In the Pipeline, medicinal chemist Derek Lowe offers guidance lots of us -- especially journalists and politicians -- could use when considering reports of the various vaccine trial results we can expect to hear about in the not-so-distant future.

He starts with some words of caution, which strikes me as appropriate, given that panic seems to be the norm:

Image by the CDC, via Unsplash, license.

[W]hat if the first vaccine results aren't very impressive? This could happen. I'm really hoping it doesn't, but anyone in the business will tell you that you don't know what efficacy is really going to be like until you run an efficacy trial, and that goes for vaccines as much as for anything else. I will say that the available biomarkers (antibodies and T cells) are much stronger in vaccine work than they are in many other areas, but on the other hand, it's immunology. Which is full of fun and interesting surprises. So if the first trial to really give a solid efficacy read comes in lower/weaker than we'd all like to see, my guess is that the press and the public won't take it too well. There will be a rush to "OMG We Can't Make A Vaccine To Corona" takes, I think, which will sow some despair and panic. I would expect the stock market not to take the news well, either.

But even if the first results aren't great, it doesn't mean that we're (necessarily) hosed. That's the good thing about having several different vaccines going, with different platform technologies. We are really going to have to wait and see what the various approaches are going to produce, even though "wait and see" is not exactly the zeitgeist right now. We have the different adenoviruses (and other vectors, which will come later), the inactivated-virus vaccines, the mRNA candidates, the recombinant proteins -- there's no reason to think that these are all going to come out the same, and that's going to be important to keep in mind. [bold added]

Interestingly, this comes after another warning -- against "declar[ing] the first one to read out the instant winner." (Are you listening, President Trump?) That one is, short-term, largely out of our hands, but it is one of my bigger concerns: Practically every government official from Trump down has made this pandemic worse than it had to be by abusing power based on a bizarre compound of evasion of evidence and control rituals. Declaring a "winner" in the "vaccine race" would be the perfectly horrible consummation of these -- including potentially for reasons the rest of the piece makes evident.

I, too, wish the epidemic would go away or at least fall at our first attempt, but the odds on that are very long.

And the rest of Lowe's discussion shows us as individuals why we should be patient regarding vaccines. The possibility of what he calls the "Patchwork Quilt of Efficacy" is a great example of that:

What if we get a mixture of results, with Vaccine A being pretty good, but not in older patients, while Vaccine B seems better in that cohort but is harder to roll out for distribution, while Vaccine C showed more even results over various patient cohorts but is beaten by some other candidate in any particular one, while Vaccine D was strong but definitely had more adverse events ... you see what I mean. I can easily imagine something like this happening, and the thing is, it's not just going to drop all at once. We're going to get those various results one after the other and will have to fit them into an unavoidably messy picture, adjusting our plans as more data points become available. Overall, I think it could be a serious mistake to declare a winning vaccine too early (unless something comes in just kicking coronavirus ass all over the field, which would frankly be fine), but telling everyone to wait while we see what the next ones bring is probably not going to go over well. There will be tremendous pressure to just start dosing people with anything that looks reasonable... [bold added]

And if that doesn't give you pause, keep reading.

Unless I catch this before vaccines start coming out, I tentatively plan to take one some time after one or more become widely available. But I won't do so without learning what I can about it beforehand -- and keeping an eye out for the kinds of adverse events Lowe describes and which would take time to become evident.

-- CAV