Hydrochloraquine: The back story

Under the Scope

Dr. Risch, professor of medicine at Yale University, recently published a review of the combination of Hydrochloraquine (HCQ), zinc and Azithromyasin for high risk, but not acutely ill patients infected with Covid-19. Dr. Risch was careful not to include severely ill patients, as prior studies had shown HCQ to have limited efficacy in patients with florid disease. In this subset of patients, there was a dramatic increase in patient survivability when treated with HCQ and AZI. Dr. Risch was the first to do an epidemiological review of the drug combination in this selective cohort of patients.

Dr. Perry Wilson, also a fellow professor at Yale, published a response to Dr. Risch’s study.

Dr.Wilson reviewed five randomized trials of HCQ which showed no beneficial effect from the use of HCQ. However, three of his five trials involved acutely ill patients with florid disease, those specifically and pointedly excluded from Dr. Risch’s review. Furthermore, none of Dr. Wilson’s randomized trials included zinc ... a known key mineral for HCQ efficacy. Dr. Wilson addressed the lack of zinc by saying it falls “into the ‘no true Scotsman’” land of HCQ studies: Any negative study can be dismissed with “you gave it too early,” “not enough,” “without zinc,” “on Sundays,” or whatever dismissive, snarky and ignorant retort indeed to a fellow faculty member. If one is going to challenge a paper claiming results with a defined cohort of patients, then the battle is over this defined group, not a different group. What are they teaching at Yale?

The point is that these are two smart professors from the same university talking, if not shouting, past each other about the effectiveness of a drug that has been given to millions since the beginning of the Covid-19 pandemic. Determining the effectiveness of HCQ and when to use it during the course of Covid-19 infection is literally a life-and-death issue. So why is this so complicated?

How we got into this cacophonous morass is the real untold story.

At the beginning of the Covid-19 pandemic a small company, Surgisphere, collected and analyzed data from 671 hospitals on six continents with the goal of addressing the efficacy and effectiveness of HCQ. The number of patients (97,000), number of hospitals and the breadth of data analyzed was astounding — and all from a company with five employees, including the three physician owners. The data Surgishere produced was analyzed in conjunction with Harvard University and University Hospital Zürich with subsequent publications in both The Lancet and The New England Journal of Medicine (NEJM) which showed that HCQ’s use in Covid patients was ineffective and placed patients at high risk for cardiac arrhythmias.

Faced with this new data, the World Health Organization led the way, terminating randomized controlled trials of HCQ. The data crunching abilities of Surisphere was revolutionary ... or was it?

One would think that collecting patient data from hospitals would be easy, but it isn’t. Hospitals have different computer systems that require interfaces to be built to access data. Once an interface is built, someone has to find out where a specific test or observation is stored and create the software to “pull” and store this data. Creating this type of interface in Surgisphere’s timeframe would be a Herculean task for a Microsoft or Google, let alone a company with shallow pockets and five employees. How did a tiny company manage to negotiate data sharing agreements with hundreds of hospitals worldwide, bridging language, cultural and legal hurtles?

The fact of the matter is they didn’t. As one drills into Surgishere’s data, more and more problems appear.

Surgisphere’s data shows that 66 percent of its patients were treated in North America, but at dosages higher than recommended by the FDA and that are more inline with prescribing guidelines in Europe. They also report 4402 Covid patients in Africa and 561 deaths; however it is highly unlikely that that Africa would have so many electronic medical records. In Australia they reported more Covid deaths than actually occurred.

These issues led The Lancet and the NEJM to issue an Expression of Concern (EOC) because of the “ serious questions” surrounding the validity of the Surgisphere data. Well no harm no foul right? Not quite.

These publications are the two marquee medical journals in the world and as such what they publish carries gravitas. Numerous clinical trials were canceled because of the sloppy work of their editorial staff. There is now a stigma around a drug that has been safely used worldwide for over 40 years. If Dr. Risch’s epidemiological review of HCQ and it’s efficacy in his limited cohort of infected, high risk, but not severely ill Covid patients is correct, the above “marquee” medical journals are responsible for tens of thousands of unnecessary deaths.

What was that about “first do no harm”?

The question is why? The founders of Surgisphere and their motivation is easy to understand. They likely studied medical ethics with Elizabeth Holmes. For them, it was a fast buck. But harder to understand is Lancet, the NEJM and their motivation. They can’t be that sloppy; Surgisphere has been outed and savaged by online pajama-clad epidemiologists and assorted out-of-mainstream academics, because their company and data was so absurd on its face. Hey, Lancet and NEJM — outing Surgisphere was not rocket science.

A cynic might be tempted to think politics or the financial interests behind a future vaccine may be responsible for such negligence.

In the meantime, HCQ effective or not, will never get a fair shake.

Karl Gruber is a practicing surgical pathologist and a graduate of both The University of the South and the Medical University of South Carolina.