Commentary about open-label randomized controlled study of ivermectin in mild to moderate COVID-19

• Published in: IMC journal of medical science (Online) Vol. 14; no. 2; pp. 1 - 2
• Main Authors: Eduardo Ortega-Guillén, Giovanni Meneses
• Format: Journal Article
• Language: English
• Published: Ibrahim Medical College 01-01-2021
• ISSN: 2519-1721; 2519-1586

To the Editor: We have carefully read the article from Podder et al. [1] published on July 2020 at this journal (volume 14, issue 2). In this regard, the authors mentioned approval of their study by the director of the health center, but not a methodological and ethical evaluation by an institutional board. We noted that the trial is not registered in ClinicalTrials.gov, unlike the trial of e.g. Chowdhury et al. [2] from the same country (cited in the article). A board would have questioned the low statistical power of the design, as it only had 62 subjects. We consider inappropriate the choice of a negative outcome of 10-day RT-PCR test as a result in outpatients, since it already was not recommended by the WHO in June 2020 [3]. The authors excluded subjects taking hydroxychloroquine or antimicrobials other than doxycycline, which could introduce considerable selection bias because it ruled out 80% of patients with a positive RT-PCR test. Lack of concealment of the randomization sequence and systematic allocation were additional factors of bias when distributing patients to the study groups. On the other hand, the lack of blinding increased the risk of information bias, since the outcome is the absence of symptoms. But the most objectionable methodological element was the exclusion of 20 subjects after allocation, based on criteria of lack of information and time of symptoms greater than seven days, not previously defined as study exclusion criteria. We consider inadequate that the authors combined mild and moderate cases of the disease and managed both categories in a single study of outpatients, when moderate cases probably must be hospitalized or receive stricter monitoring. Since May 2020, WHO advised against the decision to administer antibiotics (e.g. doxycycline) to patients without evidence of bacterial pneumonia [4]. When calculating the coefficients of variation of the times until the patients’ recovery, high variability is found in almost all described symptoms durations. We would recommend to the authors to perform a normality contrast test (e.g. Shapiro-Wilk) to check the relevance of the t-test, due to a possible lack of a normal distribution of the data. Even for smaller subgroups (about 6 patients per group with dyspnea or fatigue) the potential utility of a test of difference of medians (e.g. Mann-Whitney U test) had to be evaluated.