(CNN) … is Wrong in so Many Ways About Hydroxychloroquine…the Facts Part 2

We continue from (CNN) Trump is wrong… About Hydroxychloroquine Studies…Facts. Part 1.

Hydroxychloroquine has taken a hit. Down, but maybe not out. We’ll use this article to explore why testing is so hard.

(Retraction Watch) Hydroxychloroquine-COVID-19 study did not meet publishing society’s “expected standard”.  About the article “Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial’, the International Society of Antimicrobial Chemotherapy  (link) states (rubric mine):

ISAC shares the concerns regarding the above article published recently in the International Journal of Antimicrobial Agents (IJAA). The ISAC Board believes the article does not meet the Society’s expected standard, especially relating to the lack of better explanations of the inclusion criteria and the triage of patients to ensure patient safety.

The IJAA is the official journal of the ISAC. Despite criticism, the article has not been retracted. Inferring the unstated, the study is too flawed and weak to establish anything, yet:

  • The article author is not accused of misconduct.
  • ISAC does not wish to discourage further studies of the same medications.
  •  ISAC cannot escape human concern about the dire threat to the world.

The delicate words in red could use some interpretation. COVID-19 has one of the most variable courses of any disease, from asymptomatic to fatal.  Ethics and triage challenge the neutrality of any human study.

So does location. (CNN) Far more people may have been infected by coronavirus in one California county, study estimates. Quoting,

The study estimated that 2.49% to 4.16% of people in Santa Clara Country had been infected with Covid-19 by April 1. This represents between 48,000 and 81,000 people, which is 50 to 85 times what county officials recorded by that date: 956 confirmed cases.

This number might not be just a testing issue. If you were to fill all the available beds in Santa Clara County, and compare outcomes with the NY hospital beds, and attempt the same care, the outcomes could be wildly different. This is why a control group is so important. And there is no answer to the words in red. There is currently no way to select study patients so they average to the same severity of disease.

In any given place, the more hospital beds are available, the less sick the patients will be on average. Even a blind study, with a control group can’t factor this out. Only big numbers in the study make a dent in it, and it isn’t foolproof.

A larger, though still small, blind trial now reports  the negative. (Medscape, 4/16) No Hydroxychloroquine Benefit in Small, Randomized COVID-19 Trial. If hydroxychloroquine is a “get up and walk” miracle, it would show in this study.

Is this the end for hydroxychloroquine? Only as a wonder drug. Nothing is set in stone. It might:

  • Have prophylactic use, hopefully at a lower level than required for malaria, where serious threat to life exists.
  • Have some effectiveness  if given within the first 48 hours of infection, requiring broad availability of rapid tests.
  • Be the research basis for a drug that concentrates in the lung.

After careful study, hydroxychloroquine might compare favorably with drug innovations of the pre-antibiotic era, the first half of the 20th century. Paul Ehrlich won a Nobel for Salvarsan, the arsenic based second cure for syphilis. (In a curious twist, the first cure for syphilis was deliberate infection with malaria.)

Next: “Get up and walk” therapy; A sample study.