Hydroxychloroquine for early treatment of COVID-19: Absence of evidence is different from evidence of absence.

In their comment about Hydroxychloroquine and “COPE” (the largest RCT so far on Hydroxychloroquine for early treatment of COVID-19), Schwartz et al. claimed that “ultimately, Hydroxychloroquine did not have clinical benefit,” and that, therefore, “we can finally close the curtains on Hydroxychloroquine for COVID-19.” These two claims are misleading.

The Relative Risk (RR) estimate from “COPE” for Hydroxychloroquine vs Placebo for COVID-19-related hospitalisation was 0.77 (95%CI [0.52–1.12]). The pooled RR estimate reported by the authors, which was updated using the data from “COPE,” was similar (RR = 0.77 (95%CI [0.57–1.04])). Although these estimates are compatible with no effect, they are also compatible with a reduction of 40% in the RR of hospitalisation. Given Hydroxychloroquine's wide availability and low cost, and that there were no safety issues in “COPE,” a RR reduction of this magnitude could represent an important clinical benefit to COVID-19 outpatients at high risk of hospitalisation, e.g., those who have comorbidities, are not vaccinated, and have no access to costly therapies. By mid-May 2022, only 16% of people from low-income countries have received at least one dose of a COVID-19 vaccine. Therefore, “COPE” was a nondefinitive RCT. Current pooled estimates are also nondefinitive, which precludes Hydroxychloroquine's routine use.

Because of much controversy since the beginning of the pandemic, Hydroxychloroquine became quite stigmatised. Now it seems that it's being entombed for good. This movement can be justified in different ways, except by the fact that a clinically meaningful benefit with this drug in the outpatient setting has been ruled out, as suggested by Schwartz et al. Absence of evidence of benefit is different from evidence of absence of benefit.

Declaration of interests

Author declared no competing interests to disclose.