08th June 2020

In a recent blog describing the huge efforts around the world to find effective treatments for COVID-19, I mentioned that the World Health Organization (WHO) had just paused studies of hydroxychloroquine after The Lancet published an observational registry study which showed some concerning results.1 This has turned into a rapidly evolving situation, so this is an update on recent events.  

The WHO’s decision to suspend trials of hydroxychloroquine was based on results in The Lancet paper by Mehra MR et al.,1 which showed that treatment of COVID-19 patients with hydroxychloroquine was associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias when compared with a control group.1 However, it appears that this study was based on a large database provided by a small US company called Surgisphere. As reported in The Guardian2 on Wednesday (June 3 – click on the link in reference 2 to read the full story), the reliability of this database has been brought into question and was the subject of an independent audit. The Lancet published an ‘Expression of concern’3 to alert readers that ‘important scientific questions have been raised about data reported in the paper by Mandeep Mehra et al.’ The following day (June 4), three of the four authors published a retraction of the study4 because they were unable to complete an independent audit of the data underpinning their analysis (the author from Surgisphere, Sapan S. Desai, was not listed in the retraction).

Another prestigious medical journal, The New England Journal of Medicine, has also published a paper from the Surgisphere database, which failed to confirm previous concerns regarding a worrying association between angiotensin-converting–enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) and in-hospital deaths of COVID-19 patients.5 This journal has also subsequently published an ‘Expression of concern’.6 

As a consequence of these developments, the WHO announced on Wednesday (June 3) that it is to resume its trials of hydroxychloroquine in patients infected with COVID-19. Only time will tell if it is effective against COVID-19, but at least it’s being given a fighting chance. This episode highlights just how important it is to maintain the highest standards in data collection, analysis, and reporting. 

References

1. Mehra MR, Desai SS, Ruschitzka F, Patel AN. Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. The Lancet, May22, 2020. Available at:  https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31180-6/fulltext 

2. The Guardian, June 3, 2020. Available at: https://www.theguardian.com/world/2020/jun/03/covid-19-surgisphere-who-world-health-organization-hydroxychloroquine?CMP=share_btn_tw 

3. The Lancet Editors. Expression of concern: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. June 3, 2020. Available at: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31290-3/fulltext  

4. Mehra MR, Ruschitzka F, Patel AN. Retraction—Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. The Lancet, June 4, 2020. Available at: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31324-6/fulltext

5. Mehra MR, Desai SS, Kuy S, Henry TD, Patel AN. Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19 [published online ahead of print, 2020 May 1]. N Engl J Med 2020; NEJMoa2007621. Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa2007621 

6. Rubin EJ. Expression of Concern: Mehra MR et al. Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19 [published online ahead of print, 2020 Jun 2]. N Engl J Med 2020; NEJMe2020822. Available at: https://www.nejm.org/doi/full/10.1056/NEJMe2020822?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed