Is there a down side to society by promoting “Hope” in hydroxychloroquine as a “game changer” for treating SARS-COVID19?
Dr. “Frank” (Anthony S.) Fauci, head of the National Institute of Allergy and Infectious Diseases, seemed to imply that there was when he publicly countered Trump’s hopeful message by saying that “the only evidence of the drug’s promise has been “anecdotal”, so you really can’t make any definitive statement about it.”[1]
Is this a true statement? Webster’s dictionary defines “anecdotal evidence” as “evidence in the form of stories that people tell about what has happened to them.” Ironically, CNN declaring that “chloroquine is dangerous” based on a “story” told by people [2] who allegedly took what they thought was the same drug outside the care of a physician is a more accurate example of making unsound conclusions based on “anecdotal evidence.”
However, Trump’s message of hope that hydroxychloroquine may represent a “game changer” in the treatment of SARS-COVID19 was actually based on a growing body of published scientific evidence. For example, the drug’s mechanism of action as well as its ability to function either as a prophylactic or as a treatment in primate cells infected with SARS-CoV was published in Virology Journal in 2005 by scientists from the CDC[3]. Their paper titled, “Chloroquine is a potent inhibitor of SARS coronavirus infection and spread” has since been cited by 123 scientific publications from all around the world. But the real excitement came from a recent clinical trial conducted in France and accepted for publication by scientific peer review this week [4].
The prominent French scientists found that a more potent and less toxic version of chloroquine called hydroxychloroquine, when combined with azithromycin (a common antibiotic) “virologicaly cured” 100% of the patients (n=6) treated with the combination by day 6 compared with 57.1% in patients treated with hydroxychloroquine only (n=14), and only 12.5% in those patients who were untreated (n=16). The investigators concluded that these “results are promising and open the possibility of an international strategy for decision-makers to fight this emerging viral infection in real-time even if other strategies and research including vaccine development could also be effective, but only in the future. We therefore recommend that COVID-19 patients be treated with hydroxychloroquine and azithromycin to cure their infection and to limit the transmission of the virus to other people in order to curb the spread of COVID-19 in the world.”
While these "promising" results came from a “controlled” scientific clinical trial, the numbers of patients in the trial were low, patients were not “randomized” to treatment groups, and patients were not “blinded” to what they were being treated with. Why are such details important to consider when interpreting the results from a clinical trial? As a general rule of thumb, at least 30 patients should be randomized to each treatment group to ensure that demographic differences (e.g. age, sex, ethnic background) are equally distributed across groups. Smaller group sizes increase the probability that treatment effects are influenced by other variables. In clinical trials required for FDA drug approval, patients must be “blinded” from knowing whether they are receiving an active pill (drug) versus an inactive sugar pill (placebo). Blinding is done to ensure that “placebo effects" are equally distributed across groups.
What is a “placebo effect"? The most consistent and replicated finding in all clinical science is that around 30% of any given population treated for a disease will get better simply because they believe they are being treated with a “cure.” Thus, in the French trial discussed above, we can reliably assume that up to 30% of those who were “cured” got better simply because they believed they would (“hope”). When a society is faced with a potentially fatal disease for which no known cure exists, why exactly would we not want to encourage placebo effects? Something to think about…
References:
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https://www.washingtonpost.com/nation/2020/03/23/coronavirus-trump-anthony-fauci/
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https://www.cnn.com/2020/03/23/health/arizona-coronavirus-chloroquine-death/index.html
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Martin J Vincent, Eric Bergeron, Suzanne Benjannet, Bobbie R Erickson, Pierre E Rollin, Thomas G Ksiazek, Nabil G Seidah, Stuart T Nichol. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread Virol J. 2005; 2: 69. DOI: 10.1186/1743-422X-2-69
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Gautret P, Lagier J, Parola P, Hoang V, Meddeb L, Mailhe M, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. International Journal of Antimicrobial Agents. 2020 In Press.