therapy review work

1. Critical Appraisal of Article on Therapy
US Trial on Remdesvir : Final report
24th
November 2020
Citation: Beigel LH, Tomashek KM et al. Remdesvir for COVID 19: Final report.
DOI: 10.1056/NEJMoa2007764.
Patients: Adults who were hospitalized with Covid-19 and had evidence of lower respiratory
tract infection from 60 Trial sites from 10 countries across the world.
Intervention: Remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up
to 9 additional days)
Control: Matching Placebo Injection
Outcome: Primary outcome was the time to recovery, defined by either discharge from the
hospital or hospitalization for infection-control purposes only. (Defined as the first day,
during the 28 days after enrollment, on which a patient met the criteria for category 1, 2, or 3
on the eight-category ordinal scale. ). Secondary outcomes included 1).Case fatality ,
2).Time to improvement of one category and of two catego- ries from the baseline ordinal
score; 3). Clinical status as assessed on the ordinal scale at days 3, 5, 8, 11, 15, 22, and 29; 4).
Mean change in status on the ordinal scale from day 1 to days 3, 5, 8, 11, 15, 22, and 29; 5).
Time to discharge
Assessment of Internal Validity
1. Was the Design appropriate : Yes
The trial was Randomized Control Trial and as such is appropriate to evaluate intervention
with Remdesvir therapy in COVID 19 infection.
2. Was there any Conflict of Interest No
The study was done by National Institute of Health in USA and no conflict of interest is
likely to be present
3. Did the Randomization Work Yes
Random Allocation stratified by site of study was used. The base line variables and are given
in Table 1 shows all prognostic factors are equally distributed in the two groups studied.
4. Was the Study Blinded Yes
The study was double Blind RCT and as such measurement bias is unlikely to have occurred
in the study. Potential bias related to soft outcome of time to recovery was assessment of
clinical status was compensated by developing standardized outcome measures in the study
centres.

2. 5. Where all patients followed up till end of the study Yes
There were only 15 patients (1.4% 15/1062) who were lost to follow up till the end of the
study. The investigators used both Intention treat analysis and per protocol analysis to
evaluate the results.
Conclusion Internal Validity : The study has been done exceptionally well
and has very good internal validity.
Results of the Study
Primary outcome: Those who received remdesivir had a median recovery time of 10 days
(95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among
those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by
a log-rank test).
Secondary outcome: 1).patients who received remdesivir were found to be more likely than
those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95%
CI, 1.2 to 1.9, after adjustment for actual disease severity).
Kaplan–Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by
day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73;
95% CI, 0.52 to 1.03).
Potential NNT for Survival @ 1 month = 100/ (15.2-11.4)=26. (CI: hazard ratio 0.52-
1.03).This means NNT may be as low as 14 people if you repeat the study. Sub group
analysis showed that White occasions and starting Remdesvir before 10 days had higher
recovery rates than other race groups and late treatment.

3. Questions on Generalizability
1. Are patients similar to your own? Yes
There seems to be substantial difference in disease severity across regions of the world.
However being a large multicounty study, the generalizability of the results seem to be good.
2. Are all relevant outcomes measured Yes
Though it would have been nice to have case fatality as the primary outcome. All relevant
outcomes have been measured validly.
3. Will you give Remdesvir for COVID patients under your Care YES
Based on this well conducted RCT showing consistent benefit across sub groups which is
generalizable across populations. I would continue to give Remdsvir give Remdesvir to any
COVID patient benign admitted for mild to moderate disease for its potential benefit on
mortality and morbidity.
Dr.Kurien Thomas MBBS, MD, MSc
Professor and Head
Department of Medicine
Pondicherry Institute of Medical Sciences