Tuesday, August 25, 2020

Coronavirus - convalescent plasma

The FDA has granted emergency use authorization (EUA) to convalescent plasma to treat hospitalized patients with Covid-19 (link). This is plasma containing antibodies drawn from persons who had Covid-19 and have fully recovered.

A Wall Street Journal op-ed calls the FDA's decision good. The op-ed being behind a paywall, some reading this may only be able to see the start of it. Hence, the following in italics are some excerpts. 

This is what occurred with the anti-malaria drug hydroxychloroquine and now is happening with convalescent plasma, which the FDA on Sunday granted “emergency use authorization” (EUA). Mr. Trump was wrong to tweet over the weekend that “the deep state” at the FDA was thwarting development of therapies and vaccines to sabotage his re-election.

There’s no evidence for his claim or that the FDA is making decisions based on anything but the science. There is, however, ample evidence that convalescent plasma may be effective and that the potential benefits outweigh the risks. This is the FDA standard for EUAs, and the agency was right to increase patient access to the potentially life-saving therapy.

But individuals produce varying levels and types of antibodies in response to viruses, so convalescent plasma from some recovered patients will be more effective. This makes it especially hard to do randomized trials with control groups. The two randomized placebo trials on convalescent plasma were inconclusive.

The evidence for convalescent plasma relies on more than a dozen observational studies and clinical trials that don’t meet the randomized placebo standard. 

Current evidence suggests that benefit is most likely in patients treated early in the course of the disease (e.g., prior to intubation). This make sense. Hospitalized patients in the early stages of the disease tend to have low levels of lymphocytes that produce antibodies. Infusing them with more antibodies probably helps. But patients who must be intubated may be suffering from a cytokine inflammatory storm, which mere antibodies won’t calm.

They [others, e.g. The New York Times] want evidence from gold-standard clinical trials, but these are hard to pull off in a pandemic and often yield conflicting results.

Thousands typically need to be enrolled to prove statistically significant benefits, and trial designs obscure benefits among patient subsets. It’s unlikely that any treatment will show an aggregate benefit among all sick patients because people suffer different symptoms at different stages of the disease.


Of course, and like the op-ed says, others have lambasted the decision, such as The New York Times. What else should one expect from that source? Again, the following in italics are excerpts.

F.D.A. ‘Grossly Misrepresented’ Blood Plasma Data, Scientists Say

But scientists were taken aback by the way the administration
[President Trump, Azar of HHS, Hahn of FDA] framed this data, which appeared to have been calculated based on a small subgroup of hospitalized Covid-19 patients in a Mayo Clinic study: those who were under 80 years old, not on ventilators and received plasma known to contain high levels of virus-fighting antibodies within three days of diagnosis. 

The WSJ op-ed compared the plasma treatment to the treatments dexamethasone and  remdesivir. The two drugs are for more serious cases, but they haven't clearly passed a gold standard either. The New York Times article said nothing about those drugs and them versus the gold standard. It seems the gold standard is for things the NYT doesn't like, but not for things the NYT does like.

Update 8/26: FDA Commissioner Stephen Hahn issues mea culpa for his plasma treatment claims, saying he had overstated the benefits of convalescent plasma as a treatment of coronavirus at a news conference last weekend with President Trump (link).

Update 8/29: A key person behind Stephen Hahn's apology was removed (reassigned, not fired) from her public relations position (link).

No comments:

Post a Comment