key: cord-0028597-1ravn5ko
authors: Murthy, Srinivas
title: The authors respond to “Concerns about subgroup analyses and reason for stopping remdesivir trial”
date: 2022-03-14
journal: CMAJ
DOI: 10.1503/cmaj.81278
sha: 413d40e3c72d94e9a0dbe961ea606c58339552a1
doc_id: 28597
cord_uid: 1ravn5ko

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We thank Dr. Vijayaraghavan for the letter 1 in response to our article. 2 The Solidarity trial (NCT04647669) stopped enrolment of patients on Jan. 29, 2021, because of a lack of available product with which to continue randomization at a rapid pace, not an interim analysis or data safety monitoring board (DSMB) recommendation. The Can ad ian Treatments for COVID19 (CATCO) trial (NCT04330690) is an independent national trial with an independent steering committee and DSMB; drug was supplied through available hospital supply. The CATCO trial continued to enrol patients until Apr. 1, 2021, because without new data on effectiveness of the study medica tion from either Solidarity or another trial, equipoise remained, there were substantial numbers of patients with COVID19 in Can ada still eligible for the trial, and there was no information upon which the steering committee or DSMB could yet recommend stopping enrolment to the remdesivir com ponent. Enrolment continued in CATCO until the Solidarity trial had a data set that was approaching readiness for analysis, and a decrease in hospital admissions due to COVID19 in Canada.

We reported no statistically significant difference in the outcome of inhospital mortality between study groups (19% for those treated with remdesivir, 23% for those in the control arm, relative risk [RR] 0.83, 95% CI 0.67-1.03). 2 It is possible that this effect is limited by lack of power and will be better clarified in the full Solidarity trial when it is published. There was a dif ference in the secondary outcomes of need for new mechanical ventilation, oxygen free days at day 28 and ventilatorfree days at day 28. At the sample size achieved, it is unlikely that these were due to chance and these are consistent with the final report of the ACTT1 (the Adaptive COVID19 Treatment Trial) study. 3 We evaluated the influence of patient characteristics, dura tion of illness and baseline severity of ill ness on the primary outcome of inhospital mortality in Figure 3 of the primary publi cation. 2 Although the difference in mortal ity was not statistically significant, there was a consistent nonstatistically signifi cant signal of lower odds of dying among those treated with remdesivir in most sub groups, including timefromsymptom onset at enrolment. As the largest trial to report the impact of duration of symp toms on outcomes (including the larger Solidarity trial, which did not collect this variable), we believe the lack of difference across duration is an important finding. Future post hoc analyses will look at symptom duration as a continuous vari able to determine whether there is any association with very early or very late treatment with remdesivir efficacy.

Concerns about subgroup analyses and reason for stopping remdesivir trial

Remdesivir for the treatment of patients in hospital with COVID19 in Canada: a randomized controlled trial

Remde sivir for the treatment of COVID19 -final report

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