October 5, 2020

expert reaction to RECOVERY trial results for use of lopinavir–ritonavir in treating hospitalised patients with COVID-19

Research, published in the Lancet, reports on the use of lopinavir–ritonavir in treating hospitalised patients with COVID-19.

Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine, said:

“The publication of this paper shows the outstanding merits of having large, relatively simple, randomised trials of treatments. It is a scandal that this approach has not been replicated worldwide in order to capture a very much larger proportion of those admitted to hospital with Covid-19. Had this been done we would have had much more rapid and much higher quality answers to vital clinical questions about treatment.

“No trial can exclude the smallest possible benefit, unless it convincingly shows harm. The confidence interval limits have to all be above 1 to show no benefit at all is likely; this trial on its own has a lower confidence limit on mortality of 0.91, which says that, while unlikely a 9% benefit might just be possible.  With the note that the results from WHO SOLIDARITY trial are in line with these findings, that lower confidence limit will become close to 1 and so even smaller benefits are excluded when the results will be combined. Together they essentially provide a definitive answer to the overall question.

“The progress of disease from initial infection to very serious outcomes have different things going on, so some drugs work early but not later (like remdesivir it seems) and others the reverse (like dexamethasone it appears). It is clear that the combination tested here does not show any hints of benefit either in those treated early after symptom onset or those treated later.

“One thing not generally commented on is the constitution of the Data Monitoring Committee. Especially in a platform trial of this nature, the members of that committee must be wise and experienced. For this trial the members are well known as outstanding in their experience of monitoring data.”

‘Lopinavir–ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial’ by the RECOVERY collaboration Group was published in The Lancet at 23:30 UK time Monday 5 October.

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19

Declared interests

Prof Stephen Evans: “No conflicts of interest in relation to this paper.  I am funded (1 day/week) by LSHTM.  They get funding from various companies, including Astra Zeneca and GSK but I am not funded by them, I have no involvement in obtaining funding from them and I am not an investigator or any grants obtained from them.  I am the statistician to the “meta-Data Safety and Monitoring Board” for CEPI.  I will probably be paid for my attendance at meetings and expenses for travel.”