Institutions are conducting only observational studies on HCQs with small sample size to know the efficacy in COVID-19 patients. As of now we got mixed results. The need of the hour is to conduct a large sample size randomized, blinded clinical trial which will give a clear picture about its efficacy in COVID-19 patients.

No, from a clinical decision-making standpoint, observational studies are never enough, no matter how properly made, to determine definitive relative benefit. As the current paradigm stands in clinical research for interventions, the randomized controlled trial design remains the standard in terms of generating actual and direct prospective data. Generally speaking, ideally, the ultimate study design that can be used to assess definitive relative benefit are systematic reviews, preferably with meta-analyses, of numerous randomized controlled trials addressing the same clinical question in an adequately similar manner.

Observational studies, at best, only provide tentative data.

Also, randomized controlled trials are now being attempted in multiple sites around the world, so there is no need anymore to add to the noise by conducting observational trials at this point. The results are not promising for the particular intervention you mentioned.

https://www.cebm.net/covid-19/hydroxychloroquine-for-covid-19-what-do-the-clinical-trials-tell-us/

If we really want to know the efficacy of hydroxychloroquine, a large-cohort, multi-center, blinded RCT against placebo is necessary. An observational study does not have the power to answer this research question.

This should ideally be planned as a randomized clinical trial where HCQ+Standard of Care (SoC) for prevention of COVID19 is to be compared with SoC alone provided both the groups are exposed to similar risk settings.

Efficacy and safety of HCQ in the prophylaxis of SARS-CoV-2 should be assessed through clinical trials. It can be an investigator's sponsored. Electrocardiographic control should be scheduled, doses and treatment duration carefully established.

Dear Joe Graymer, I'm aware of the results of small CT and some observational studies. There is no evidence of efficacy based on these studies. Controlled CT are needed to give an answer.

En mi modesta opinión es un ensayo clínico, porque se va a probar su eficacia.El método es experimental, y la observación hace parte de la fase de la primera fase.Además se requiere del consentimiento informado por razones de ética.

There are also covid positive cases under the prophylaxis.

If you want clinical trial for a drug you have to be sure that an infection in the environment (exposure ) in order to measure the drug can act prophylaxis or not.

Dont forget the cross positive in this case.

An observational study is a CT? What control would you use in an observational study?

Hydroxychloroquine alone or with Azithromycin for COVID-19: No benefit but increased risk

No significant benefit with Hydroxychloroquine and Azithromycin either alone or in combination on in-hospital mortality in COVID-19 patients in USA. However, increased risk of prolonged QT-interval with risk of ventricular arrhythmias.

References

Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State

https://jamanetwork.com/journals/jama/fullarticle/2766117

Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19

https://www.nejm.org/doi/full/10.1056/NEJMoa2012410

Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing

Positive for Coronavirus Disease 2019 (COVID-19).

https://www.ncbi.nlm.nih.gov/pubmed/32356863

Clinical trial

If you want to ensure its efficacy and safety then go for CT so that everyone has to be understand.

a joe Graymer: NO ENTENDI NADA DE SU RESPUESTA!!!!!!

HC is not allowed to be used as a prophylaxis, considering the serious side efffect on cardiovascular. It may prlong the QT interval.

Observational studies are not rigorous enough to provide information required to determine efficacy and safety, so a clinical trial is necesary. Hoewever, there would be too many confounders regarding the elimination of other protective factors against covid-19, unless one purposefully exposed people to the corona virus of similar virulence in the same titers, which would be unethical. There are too many unknown variables to determine which patients will get severe disease or die, when exposed to the virus. It would require exposing a control group to the virus without treatment. Which is equally unethical. For how long would one continue giving hydroxychloroquine to prevent infection. The longer you give it, the higher the chances of side effects. Especially in people with cardiopulmonary disease, who happen to be the people at highest risk of mortality and mobidity from covid-19. Most treatment protocols are anecdotal because none of the studies have conducted randomized controlled trials that are considered the gold standard.

The lack of proper progression from in vitro studies feeding into in vivo and animal studies, before commencing human studies, has created loopholes that are supposed to be filled by previous studies. I think scientist have rushed through critical foundational concepts that are meant to prevent the current situation, where no one is sure of anything and everyone is changing the opinions with additional information that is rarely verified. We have lost credibility by deviating from well known fundamental principles that ensure patient/participant safety and efficacy of interventions. I think the reall answers will come up when the situation calms down and we start applying scientific principles of study designs, data analysis and comprehensive information from all centers, that will provide observational analysis for actionable bench-to-bedside research. For no, clinical trials seem premature with the information at hand. The fact that most infections are self limiting makes it hard to determine if it is the intervention or the natural immune response that is responsible for the outcome.

Should we consider Hydroxychloroquine a dead horse for treatment of COVID-19?

Added to previous studies of lack of benefit, but increased risk as posted by me previously, a recent study on mortality of COVID-19 with hydroxychloroquine with or without Azithromycin did not any benefit, but increased mortality (2).

1. https://jamanetwork.com/journals/jama/fullarticle/2766117

2. https://www.nydailynews.com/coronavirus/ny-more-deaths-no-efficacy-of-malaria-drug-found-in-coronavirus-study-20200421-v4k45zwp5zc57dobqsa4xqexea-story.html