Without evidence of benefit, an intervention should not be presumed to be beneficial or safe.

- Rogue Medic

Is Hydroxychloroquine Effective Against COVID-19?

     
As with any popular treatment, there are plenty of people who want us to ignore the research, or to focus on giving people hope. That is not a reasonable, or ethical, approach to medicine. That is not even a medical approach to medicine. If we lower our standards enough, we can claim that everything works, but that would kill a lot more people than only using treatments based on EBM (Evidence Based Medicine). Should we make excuses for lowering our standards, and killing people, or should we insist on raising our standards?

There is currently a pandemic, so there is a bit of a rush to find something that works, which some people mistake for a need to provide hope. If you want hope, you can pray and there should not be any harmful effects of praying. However knowing that you were being prayed for by others has been associated with a significantly higher incidence of complications. In other words, praying for yourself or others is fine, but telling others that you are going to pray for them is probably harmful, even though your intent is to help.[1]

The reasonable way to look at taking medicine is take only those treatments that have been demonstrated to improve outcomes for people with the studied diagnosis, when you have that diagnosis. Everything else is a crap shoot, where you don’t even know the risks – and there probably is no benefit.

Why do I state that the risks to the person taking the treatment are unlimited, but the benefits probably do not exist?

That is the history of the study of treatments. Almost everything proposed as a treatment has been more harmful than beneficial. It would be nice if this were not true, but reality doesn’t care about being nice. All of alternative medicine falls into the category of probably more harmful than safe and unlikely to be of any benefit, other than a benefit to the finances of the person selling the alt med.

Is hydroxychloroquine alternative medicine? Hydroxychloroquine is approved as real medicine for malaria, lupus erythematosus, and rheumatoid arthritis.[2] For these diagnoses, hydroxychloroquine is not alternative medicine. For everything else, the use is off-label, which is a legal way of saying alternative medicine, as far as the FDA (Food and Drug Administration) is concerned. Sometimes off-label use can be supported by good evidence, but the treatment has not been submitted to the FDA for approval for that diagnosis, but that is not the case with hydroxychloroquine. The FDA issued an EUA (Emergency Use Authorization) for hydroxychloroquine limited to adults and adolescents who weigh 50 kg (approximately 110 pounds) or more, who were hospitalized with COVID-19, and for whom participation in a clinical trial was not available, or participation was not feasible.[3]

Why are those limitations important?

1. If a treatment is effective, diverting patients from clinical trials will delay learning that the treatment is effective, which will significantly decrease the number of lives saved.

2. If a treatment is not effective, diverting patients from clinical trials will delay learning that the treatment is not effective, which will significantly decrease the number of lives saved, because patients are receiving a useless distraction from effective treatment.

3. If a treatment is harmful, which is much worse than just being not effective, diverting patients from clinical trials will delay learning that the treatment is harmful, which will significantly increase the number of patients killed.

All of those results – and those are the possibilities – are ignored by those who reject research. No treatment, however good, will be purely beneficial. All treatments have adverse effects. however, the reverse of that is not true. A treatment that is harmful often does not provide any benefit.

The odds are always against the patient. Any doctor trying to just do something is endangering patients. Kitchen sink medicine (throwing everything at the patient, just in case) has always been bad medicine.

There is a good discussion of the evidence in two podcasts:

15. Covid-19: Is There a Case for Hydroxychloroquine?
Stimulus with Rob Orman, MD (who also hosts the ERCast)
July 30, 2020
Podcast page

Dr. Orman does not specifically mention the Arshad study, which claims to show a benefit in patients treated with HCQ (HydroxyChloroQuine), AZM (AZithroMycin), and HCQ+AZM (HydroxyChloroQuine + AZithroMycin), but that does not change the conclusion of an examination of the evidence.[4]


COVID-19 Treatment Update: Can We Just Stop Wasting Time on Hydroxychloroquine
Written by Salim Rezaie
July 6, 2020
Podcast page

Here is the most important point from Salim Rezaie about the outcomes from the Arshad study:

As most patients in this trial receiving HCQ or HCQ + AZM received steroids and the patients receiving AZM alone or neither therapy had far fewer patients receiving steroids, the likely mortality benefit of this trial is due to the steroids and not the HCQ or HCQ + AZM


Dr. Rezaie concludes: This study should not change clinical practice of not prescribing these medications.

The Arshad study is being used by proponents of hydroxychloroquine alternative medicine to try to contradicting higher quality research, which is the reason it is not real medicine. When there is only low quality evidence, we should be cautious in recommending any treatment. When the high quality evidence shows that the low quality evidence is misleading, we should ignore the low quality evidence until there is high quality evidence to support the findings of the low quality evidence. Don’t expect that to happen.

The reason most medical research is overturned is the reliance on low quality evidence.[5], [6], [7], [8]


Footnotes:

[1] Study of the Therapeutic Effects of Intercessory Prayer (STEP) in cardiac bypass patients: a multicenter randomized trial of uncertainty and certainty of receiving intercessory prayer
Herbert Benson 1, Jeffery A Dusek, Jane B Sherwood, Peter Lam, Charles F Bethea, William Carpenter, Sidney Levitsky, Peter C Hill, Donald W Clem Jr, Manoj K Jain, David Drumel, Stephen L Kopecky, Paul S Mueller, Dean Marek, Sue Rollins, Patricia L Hibberd
Am Heart J. 2006 Apr;151(4):934-42. doi: 10.1016/j.ahj.2005.05.028.
PMID: 16569567

Our study had 2 main findings. First, intercessory prayer itself had no effect on whether complications occurred after CABG. Second, patients who were certain that intercessors would pray for them had a higher rate of complications than patients who were uncertain but did receive intercessory prayer.



[2] Hydroxychloroquine Sulfate tablet
INDICATIONS AND USAGE
Daily Med
FDA Label


[3] Frequently Asked Questions on the Revocation of the Emergency Use Authorization for Hydroxychloroquine Sulfate and Chloroquine Phosphate
FDA
Page as PDF download

Q. Why did FDA grant the EUA for hydroxychloroquine sulfate (HCQ) and chloroquine phosphate (CQ) for the treatment of COVID-19 initially?
A. On March 28, 2020, BARDA requested and FDA issued an Emergency Use Authorization (EUA) for emergency use of oral formulations of chloroquine phosphate (CQ) and hydroxychloroquine sulfate (HCQ) for the treatment of COVID-19. Based on the scientific information available to FDA as of that date, the Agency determined that CQ and HCQ may be effective in treating COVID-19 and that the known and potential benefits of CQ and HCQ outweighed the known and potential risks for this use. The agency limited the use of authorized products to adults and adolescents who weigh 50 kg (approximately 110 pounds) or more, who were hospitalized with COVID-19, and for whom participation in a clinical trial was not available, or participation was not feasible.



[4] Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19
Samia Arshad,a Paul Kilgore,b,c Zohra S. Chaudhry,a Gordon Jacobsen,e Dee Dee Wang,d Kylie Huitsing,a Indira Brar,a George J. Alangaden,a,c Mayur S. Ramesh,a John E. McKinnon,a William O’Neill,d Marcus Zervos,a,c,⁎ and Henry Ford COVID-19 Task Force1
Int J Infect Dis. 2020 Aug; 97: 396–403.
Published online 2020 Jul 2. doi: 10.1016/j.ijid.2020.06.099
PMID: 32623082

PMCID: PMC7330574 (Free Full Text from PubMed Central)


[5] Why Most Published Research Findings Are False
John P. A. Ioannidis
PLoS Med. 2005 Aug; 2(8): e124.
Published online 2005 Aug 30. doi: 10.1371/journal.pmed.0020124
PMID: 16060722

PMCID: PMC1182327 (Free Full Text from PubMed Central)

The probability that a research claim is true may depend on study power and bias, the number of other studies on the same question, and, importantly, the ratio of true to no relationships among the relationships probed in each scientific field. In this framework, a research finding is less likely to be true when the studies conducted in a field are smaller; when effect sizes are smaller; when there is a greater number and lesser preselection of tested relationships; where there is greater flexibility in designs, definitions, outcomes, and analytical modes; when there is greater financial and other interest and prejudice; and when more teams are involved in a scientific field in chase of statistical significance.



[6] Evidence-based de-implementation for contradicted, unproven, and aspiring healthcare practices
Vinay Prasad and John PA Ioannidis
Implement Sci. 2014; 9: 1.
Published online 2014 Jan 8. doi: 10.1186/1748-5908-9-1
PMID: 24398253

PMCID: PMC3892018 (Free Full Text from PubMed Central)

Abandoning ineffective medical practices and mitigating the risks of untested practices are important for improving patient health and containing healthcare costs. Historically, this process has relied on the evidence base, societal values, cultural tensions, and political sway, but not necessarily in that order. We propose a conceptual framework to guide and prioritize this process, shifting emphasis toward the principles of evidence-based medicine, acknowledging that evidence may still be misinterpreted or distorted by recalcitrant proponents of entrenched practices and other biases.


[7] Observational studies often make clinical practice recommendations: an empirical evaluation of authors’ attitudes
Vinay Prasad 1, Joel Jorgenson, John P A Ioannidis, Adam Cifu
J Clin Epidemiol.
2013 Apr;66(4):361-366.e4.
PMID: 23384591   DOI: 10.1016/j.jclinepi.2012.11.005

It is common to see new studies contradict previous adopted standards of care [25,26]. Even the results of highly cited studies can be refuted [7], and the replication rate tends to be low for claims made from observational designs [7]. We have previously noted that the most common correlate for reversal of standards of care was the original adoption of a practice based on nonrandomized evidence alone [27]. The studies examined here offer many recommendations that may be precarious or erroneous. If adopted, such practices may need to be reversed in the future after having been detrimental to health, health finances, and the reputation of medical science.



[8] Contradicted and initially stronger effects in highly cited clinical research
John P A Ioannidis
JAMA. 2005 Jul 13;294(2):218-28. doi: 10.1001/jama.294.2.218.
PMID: 16014596   DOI: 10.1001/jama.294.2.218

Free Full Text from JAMA

Of the 45 eligible highly cited studies with efficacy claims (Table 2), 7 (16%) were contradicted by subsequent research, and another 7 (16%) were found to have initially stronger effects. In all these 14 cases (BOX 1), subsequent studies were either larger or better controlled (randomized vs a nonrandomized original study). The findings of 20 highly cited articles (44%) were replicated (also with a larger sample size in subsequent research compared with the original highly cited study) and 11 (24%) had remained largely unchallenged.58-78



.

Speak Your Mind