I suppose that I’m going to have to say something about yesterday’s convalescent plasma announcement. First, the medical aspects: in my view, for what that’s worth, convalescent plasma is likely to be at least somewhat helpful to hospitalized coronavirus patients. I think that its safety profile is likely to be good as well, and I really have no problem with it being used.
There are downsides. It’s labor-intensive, since it needs blood donation from recovered patients, processing of their blood to obtain the plasma, pooling of these plasma samples and re-portioning all this for dosing, and finally i.v. administration to the current patients themselves. None of these are onerous by themselves, but it does add up, and remember that you need plenty of donors to make an impact, given how much plasma needs to be dosed. Another problem: as we have seen from the convalescent plasma comparators in the vaccine trial data, the antibody levels in these plasma donations is quite variable. Thus the need for pooling, because otherwise you would have a wildly differing product. Many of the convalescent plasma antibodies that will be given to the current patients will be of no use against the coronavirus (they’re random or targeted to other pathogens entirely, so ideally you’d want donors who are still showing a high neutralizing titer. What I don’t know is whether every donor is going to be screened in this way (which adds more to the labor, of course). You run the risk of having a few donors who have a great antibody profile being diluted down by a larger number of people with low titers, of course.
All of these considerations are taken care of by dosing monoclonal antibodies instead of the isolated antibody fractions, and as mAbs become more available, I would expect convalescent plasma to become less widely used. There are costs and production aspects to rolling out mAbs, but biologically, they are the perfected version of what convalescent plasma is trying to achieve.
But that brings up the second topic, the regulatory and organizational aspects of all this. It’s nearly September. We’ve been dealing with this pandemic for months now in the US, and let’s be honest: convalescent plasma is generally considered an emergency stopgap while you try to come up with something else. The problem is that we still haven’t generated any controlled clinical data on how useful it is. The Mayo-led data that were talked about during yesterday’s press conference had no control group, making that key question impossible to really answer. This shows the perverse danger of being too free with emergency use. If you just turn everyone loose on a bunch of therapies, they will be used under all sorts of conditions and the chances of getting a useful read on any of them go down. Look at our current situation: we have data on over 35,000 patients who have received convalescent plasma, but we still don’t have a good comparison to not receiving it. It shouldn’t have happened this way.
I know that there was a figure of 35% being helped/saved by the plasma treatment being used at yesterday’s press conference, but unfortunately, that’s just plain wrong. FDA Commissioner Hahn used the phrase “35% improvement in survival”, but that merely makes him look like a fool (and like someone trying to keep his boss smiling) to anyone who’s capable of reading the actual paper, which is another nasty side effect of this whole affair. See this for more, and this: since the data do not have a control comparison group, we can make no firm statements about the benefit of the treatment, and the 35% number is a misunderstanding of what data we have. Sad but true. Update: late last night Hahn walked his statements back on Twitter. I’m glad to see that, but a broader announcement would have been even better.
Finally, that leads us to the political aspect of this, damn it all. Yesterday’s press conference was announced the night before by the White House as concerning “a major therapeutic breakthrough”. The president and his allies echoed this language, with phrases like “historic breakthrough”, “a truly historic announcement”, and so on. It wasn’t. Convalescent plasma has been used for many decades in other infectious diseases, and it was tried very early on in the first countries affected by the coronavirus. Announcing an Emergency Use Authorization this late in the game for it in the US is, as I tried to convey in the above paragraph, closer to being something that we should be vaguely ashamed about.
The hype is not helpful. The preannouncement about a major breakthrough, the apparent need for the President himself to step up and give the news (alongside the heads of HHS and the FDA, yet) – all of this is sheer public relations, and that’s not what we need to beat down this pandemic. The virus does not care about press conferences, breathless tweets, and fawning statements about leadership and vision. I’ll be up front about this: the way that President Obama inserted himself into events used to get on my nerves, but I had no idea what was coming and how bad it could get. A big effect of this plasma announcement, as far as I can tell, was to sow doubt about what the administration considers a breakthrough and what its intentions are about authorizing a vaccine before the November election. And before anyone jumps on me for that insinuation, allow me to remind you that the President himself, in his Sunday morning Twitter duties, accused the so-called “deep state” at the FDA of literally dragging their feet in trying to not get a vaccine before the election. Which was a suggestion I found false, infuriating, and as harmful as such a short statement could be to the chances of rolling out a vaccine in an orderly and medically justified way. Trump himself, in his press conference, said that it was his “very strong opinion” that the FDA had delayed a plasma EUA for political reasons. So no, we don’t need the whole process tied to electoral politics, but guess who’s losing no chances to do just that?
And guess who’s lost no chances, with these statements and more, to give the impression that he’s leaning hard on the FDA to do what he wants it to do, science be damned? Have a look at the statements by former FDA scientists in this Biocentury article on the affair: they believe that the agency is being suborned. Commissioner Hahn’s and Sec. Azar’s obsequious statements yesterday (and the mangling of the statistics to make everything look rosier) were terrible to see. And the FDA’s own web site announcement includes the phrase “Another Achievement in Administration’s Fight Against Pandemic” in the headline, which is a first, to the best of my knowledge, since the FDA is not supposed to be tied to any particular presidential administration and is not supposed to be shining anyone’s shoes. But hey, if you’re going to have someone licking them, someone else has to step in with the rag right afterwards, and they’d better snap the thing so the big guy can hear it.
Comments will be turned off on this post, for obvious reasons. We’ll get back to some science tomorrow.