Should Remdesivir Be Used for the Treatment of Patients With COVID-19? Rapid, Living Practice Points From the American College of Physicians (Version 2)



## Overview of new evidence
The evidence update identified 1 new study [bib_ref] Repurposed antiviral drugs for COVID-19-interim WHO Solidarity trial results, Who Solidarity Trial [/bib_ref]. The new study evaluated a 10-day course of remdesivir versus standard care and provides new data for all-cause mortality (critical outcome) and new need for ventilation (noninvasive ventilation, invasive ventilation, mechanical ventilation, or extracorporeal membrane oxygenation [ECMO]) among patients not requiring ventilation at the time of drug initiation (important outcome). The update also reports the final results from 1 study [bib_ref] ACTT-1 Study Group Members. Remdesivir for the treatment of Covid-19-final report, Beigel [/bib_ref] that was included in version 1 as preliminary findings (7) comparing a 10-day course of remdesivir versus placebo for the following outcomes: all-cause mortality, recovery, hospital length of stay, time to recovery, proportion of patients on mechanical ventilation or ECMO, any adverse events, and serious adverse events. [fig_ref] Table 2: Updated Evidence Summary for the Use of Remdesivir as Treatment for Patients... [/fig_ref] and the accompanying systematic evidence review summarize changes in the findings [bib_ref] Major update: remdesivir for adults with COVID-19. A living systematic review and..., Kaka [/bib_ref].
The evidence update did not identify any new evidence comparing a 5-day course of remdesivir versus placebo or standard care or a 5-day course versus a 10day course.

## Updated practice points and rationales (version 2)
patients, we have modified the practice points to specify the target patient population as hospitalized. <11, 12> presents clinical considerations. Thresholds applied to determine the magnitude of effect for critical and important outcomes, prespecified by the evidence review team, are provided in [fig_ref] Table 4: Thresholds for Determining Magnitude of Effect* [/fig_ref]. identifies additional evidence gaps. Appendix available at Annals.org) presents the data estimates supporting the practice points.

## Practice point 1: consider remdesivir for 5 days to treat hospitalized patients with covid-19 who do not require mechanical ventilation or ecmo

## Updated rationale
As in the previous version of the practice points, current evidence suggests an overall net benefit of remdesivir in patients with COVID-19 who do not require invasive mechanical ventilation or ECMO and suggests that 5 days of treatment may be as effective as 10 days, with no increase in potential harms . Despite low certainty, the SMPC judged it reasonable to provide clinical advice for the use of a 5-day course of remdesivir in hospitalized patients, particularly considering the limited availability of effective treatments for hospitalized patients with COVID-19. The language of the practice point was changed from "use remdesivir" to "consider remdesivir" to highlight the importance of clinical judgment when making decisions with individual patients about whether to begin remdesivir treatment. Given that disease severity definitions (mild, moderate, severe, and critical) vary widely among the included studies and among different organizations (for example, World Health Organization , National Institutes of Health, and U.S. Food and Drug Administration) , ACP has shifted away from the previous classifications of "moderate" and "severe" in this version. Rather than using these classifications, we use respiratory support requirements as a proxy for disease severity because we expect this to be more clinically useful given the inconsistent definitions. As a result, we have combined the previously separated practice points for patients with moderate COVID-19 and severe COVID-19 who do not require mechanical ventilation or ECMO into a single statement. Evidence is emerging about the effectiveness and harms of remdesivir in patients with COVID-19 and whether they vary by symptom duration, disease severity, and treatment duration. The following practice points are based on current best available evidence. Practice Point 1: Consider remdesivir* for 5 days to treat hospitalized patients with COVID-19 who do not require mechanical ventilation or ECMO. Practice Point 2: Consider extending the use of remdesivir* to 10 days to treat hospitalized patients with COVID-19 who require mechanical ventilation or ECMO within a 5-day course. Practice Point 3: Avoid initiating remdesivir to treat hospitalized patients with COVID-19 who are already on mechanical ventilation or ECMO. What has changed in the practice points since the last version?  Practice points shifted away from the previous classifications of "moderate" and "severe" disease to describe disease severity (when data were available) based on respiratory support requirements (e.g., no requirement, supplemental oxygen, or mechanical ventilation/ECMO). All practice points now specify the target patient population as "hospitalized" patients. Practice Point 3 was added.
COVID-19 = coronavirus disease 2019; ECMO = extracorporeal membrane oxygenation. * Remdesivir is not recommended for patients with an alanine aminotransferase level 5 times the upper limit of normal or an estimated glomerular filtration rate <30 mL/min/1.73 m 2 (see further details in .  See updated rationales and for additional details.

## Figure.
Updated evidence description. What has changed in the evidence since the last version? 10-day course vs. standard care: added 1 new study [bib_ref] Repurposed antiviral drugs for COVID-19-interim WHO Solidarity trial results, Who Solidarity Trial [/bib_ref] providing data for the following outcomes: all-cause mortality and need for mechanical ventilation/ ECMO 10-day course vs. placebo: updated with final results from 1 study (6) (preliminary results previously reported), providing final results for the following outcomes: all-cause mortality, recovery, hospital length of stay, time to recovery, need for mechanical ventilation/ECMO, any adverse events, and serious adverse events 8 One previously reported outcome (nonserious adverse events)was not reported in the final results and has been removed from this table [bib_ref] ACTT-1 Study Group Members. Remdesivir for the treatment of Covid-19-final report, Beigel [/bib_ref]. Collapsed placebo and standard care comparisons to a single control comparison 10-day course vs. control (placebo or standard care): pooled analyses added for mortality, recovery, clinical improvement, need for mechanical ventilation/ECMO, and serious adverse events Shifted away from the previous classifications of "moderate" and "severe" disease to now describe disease severity [bib_ref] Repurposed antiviral drugs for COVID-19-interim WHO Solidarity trial results, Who Solidarity Trial [/bib_ref] [bib_ref] ACTT-1 Study Group Members. Remdesivir for the treatment of Covid-19-final report, Beigel [/bib_ref] [bib_ref] Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial, Wang [/bib_ref] Note: The effect of remdesivir (10-d course vs. placebo/standard care) may vary by baseline respiratory support requirements [bib_ref] ACTT-1 Study Group Members. Remdesivir for the treatment of Covid-19-final report, Beigel [/bib_ref] [bib_ref] Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial, Wang [/bib_ref] , may not reduce mortality in patients not requiring supplemental oxygen at baseline, may result in a small reduction in mortality in patients requiring supplemental oxygen but not mechanical ventilation at baseline, and may result in a modest increase in mortality in patients requiring mechanical ventilation/ECMO at baseline.  Note: The effect of remdesivir (10-d course vs. placebo) may not vary by symptom duration (10 vs. >10 d)  [bib_ref] Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial, Wang [/bib_ref].
Moderate 5-d vs. 10-d course 2 RCTs (781) Remdesivir 5-d course may slightly reduce mortality compared with a 10-d course (9, 10) Note: The evidence is very uncertain about the effect of remdesivir in patients who progress to requiring mechanical ventilation/ECMO at day 5 (9): A 5-d course may result in a large increase in mortality vs. a 10-d course for patients who progressed to requiring mechanical ventilation/ECMO at day 5, and there may not be a reduction in mortality for patients who were receiving noninvasive positive-pressure ventilation or high-or low-flow oxygen or who were breathing ambient air at day 5 (insufficient certainty of evidence).

## Low
Recovery  (781) Remdesivir 5-d course may result in a modest reduction in serious adverse events compared with a 10-d course (9, 10) Note: The effect of remdesivir 5-d course compared with a 10-d course may vary by baseline respiratory support requirements  (9, 10): There may be a large reduction in severe adverse events for patients hospitalized with reduced oxygen levels who did not require mechanical ventilation at baseline, but there may not be a reduction in severe adverse events in patients without reduced oxygen levels on room air (10).

## Low
Continued on following page (1455) Remdesivir (10-d course) may result in a large reduction in time to recovery compared with placebo (6), but the effect is uncertain for remdesivir (10-d course) compared with standard care (10) Note: The effect of remdesivir (10-d course) may not vary by symptom duration or baseline respiratory support requirements  (6). (781) Remdesivir 5-d course may slightly reduce the proportion of patients on invasive mechanical ventilation/ECMO at follow-up compared with a 10-d course (9, 10) Note: The effect of a 5-d course of remdesivir compared with a 10-d course may vary by baseline respiratory support requirements  (9, 10): There may be a modest reduction in the proportion of patients on mechanical ventilation/ECMO among patients hospitalized with reduced oxygen levels who did not require mechanical ventilation at baseline (9, 10) but there may not be a reduction in the proportion of patients on mechanical ventilation/ECMO among patients without reduced oxygen levels on room air at baseline .

## Low

## Continued on following page

## Clinical guideline
Should Remdesivir Be Used for the Treatment of Patients With COVID-19?
The evidence update did not result in any changes to our previous overall assessment of the balance of benefits and harms. There continues to be a net benefit with both a 5-day and 10-day course compared with placebo or standard care. No new studies were identified reporting on a 5-day course; however, the results for recovery and clinical improvement were updated with longerterm results and show no changes to previous conclusions. Although the inclusion of new data resulted in a finding of little to no effect of a 10-day course on mortality (previously reported as a small reduction) and the new need for ventilation (previously not reported), there (781) Remdesivir 5-d course may modestly reduce any adverse events compared with a 10-d course (9, 10) Low COVID-19 = coronavirus disease 2019; ECMO = extracorporeal membrane oxygenation; NA = not applicable; RCT = randomized controlled trial. * Insufficient certainty of evidence: confidence is inadequate to assess the likelihood of benefit (benefit minus harm) of an intervention or its effect on a health outcome. Low certainty of evidence: confidence in the effect is limited because the true effect may be substantially different from the estimated effect. Moderate certainty of evidence: confidence in the effect is moderate because the true effect is likely close to the estimated effect, but there is a sizable possibility that it is substantially different. High certainty of evidence: confidence that the true effect is close to the estimated effect.  The certainty of evidence was not assessed for this comparison determined from a subgroup analysis.  Recovery was defined as discharge from the hospital or hospitalization for infection control purposes only in 1 RCT (6) and as discharge from the hospital or hospitalized but not requiring supplemental oxygen or ongoing medical care in 3 RCTs (8-10).  Remdesivir (5-d and 10-d courses) may not decrease the percentage of persons hospitalized between days 11 and 14 (4). || Severe adverse events reported in studies included in the evidence review [bib_ref] Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial, Wang [/bib_ref] were acute coronary syndrome, acute kidney injury, acute respiratory distress syndrome, acute respiratory failure, increased aminotransferase levels, atrial fibrillation, bronchitis, cardiac arrest, cardiopulmonary failure, increased D-dimer level, deep venous thrombosis, diabetic ketoacidosis, dyspnea, endotracheal intubation, decreased glomerular filtration rate, hemorrhage of the lower digestive tract, hypotension, hypoxia, ileus, lung abscess, mechanical ventilation, multiple organ dysfunction syndrome, respiratory distress, respiratory failure, pneumothorax, pulmonary embolism, pulmonary failure, recurrence of COVID-19, septic shock, sepsis, shock, tachycardia, thrombocytopenia, and viral pneumonia. Any adverse events reported in the studies included in the evidence review [bib_ref] Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial, Wang [/bib_ref] were acute kidney injury, acute respiratory failure, increased alanine aminotransferase level, anemia, increased aspartate aminotransferase level, increased blood glucose level, increased blood lipid levels, increased blood urea nitrogen level, constipation, hyperlipidemia, hypoalbuminemia, hypokalemia, hypotension, insomnia, nausea, increased neutrophil count, rash, respiratory failure, increased serum potassium level, reduced serum sodium level, thrombocytopenia, increased total bilirubin level, vomiting, and increased leukocyte count. Any adverse events were not identified in 1 study included in the evidence review (5).  Clinical improvement was defined as a 2-point reduction in patients' admission status on a 6-point ordinal scale (1 = live discharge to 6 = death) or live discharge from the hospital (whichever came first) in 1 study [bib_ref] Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial, Wang [/bib_ref] and as an improvement of at least 2 points from baseline on a 7-point ordinal scale (1 = death to 7 = discharged from hospital) in 2 studies (9, 10).

## Table 3. clinical considerations
Remdesivir is currently only administered by IV infusion in hospital settings or in a facility that can provide care similar to an acute care hospital setting (1). 5-d course in adults is 200 mg IV on day 1 followed by 100 mg/d for a total of 5 d (5 doses). 10-d course in adults is 200 mg IV on day 1 followed by 100 mg/d for a total of 10 d (10 doses). The practice points do not apply to pregnant women or patients with severe renal or hepatic dysfunction because they were excluded from the studies included in the evidence review. NEW: The decision to initiate treatment with remdesivir in hospitalized patients with COVID-19 should be based on clinical judgment; remdesivir should not necessarily be initiated in patients hospitalized for a primary diagnosis unrelated to COVID-19 who have incidentally tested positive for severe acute respiratory syndrome coronavirus 2. NEW: For hospitalized patients with COVID-19 whose condition worsens within a 5-d course to require supplemental oxygen but not mechanical ventilation, extending the use of remdesivir should be based on clinical judgment and the balance of benefits and harms, because current evidence is insufficient to determine whether treatment beyond 5 d improves mortality among patients who are receiving noninvasive positive-pressure ventilation or high-or low-flow oxygen or who are breathing ambient air. The effectiveness of a 10-d course of remdesivir in reducing mortality [bib_ref] Repurposed antiviral drugs for COVID-19-interim WHO Solidarity trial results, Who Solidarity Trial [/bib_ref] and time to recovery (6, 7) may not vary by age, sex, or race in hospitalized patients with COVID-19. There was not enough information to determine what other treatment interventions, including experimental or off-label medications, were given in the trials. Currently, the cost of a 5-d course of remdesivir in the United States varies by insurance status, from $2340 (Indian Health Service and the VA) to $3120 ($520/vial) (U.S. insurers, including Medicare and Medicaid). The cost for those without insurance is currently $390/vial [bib_ref] Stories @Gilead, O&apos;day [/bib_ref]. The FDA recommends that clinicians assess kidney and hepatic function at baseline and during treatment . The FDA recommends the following: 8 Not using remdesivir in patients with an estimated glomerular filtration rate <30 mL/min/1.73 m 2 .
8 Discontinuing the use of remdesivir if alanine aminotransferase levels increase to >10 times the upper limit of normal or if alanine aminotransferase elevation is accompanied by signs or symptoms of liver inflammation. The FDA reports that hypersensitivity reactions, including infusion-related and anaphylactic reactions, have been observed during and after administration of remdesivir [bib_ref] Repurposed antiviral drugs for COVID-19-interim WHO Solidarity trial results, Who Solidarity Trial [/bib_ref]. Additional adverse events include metabolic (hyperglycemia), hepatic (increased serum alanine aminotransferase and aspartate aminotransferase levels), and renal (renal toxicity) events . remains a reported benefit for recovery (modest increase), clinical improvement (modest increase), and length of stay (modest reduction), along with fewer serious adverse events (modest difference) among those treated. Further, patient compliance data from the final report of 1 study comparing a 10-day course versus placebo continue to show that a 10-day course (10 doses) was used in fewer than half of the patients receiving remdesivir (41.2%), and an even lower percentage of patients (38.1%) received fewer than 10 doses because they recovered and were discharged from the hospital [bib_ref] Remdesivir for adults with COVID-19. A living systematic review for an American..., Wilt [/bib_ref] [bib_ref] ACTT-1 Study Group Members. Remdesivir for the treatment of Covid-19-final report, Beigel [/bib_ref]. Finally, there are no new studies directly comparing a 5-day versus a 10-day course.
An important area of uncertainty relates to the use of remdesivir in patients who do not require supplemental oxygen at hospitalization, although we expect that most patients with a diagnosis of COVID-19 are admitted with respiratory signs and symptoms. A newly reported pooled subgroup analysis comparing a 10-day course versus placebo or standard care showed that there may be a small reduction in mortality among patients requiring supplemental oxygen (but not mechanical ventilation) at the time of drug initiation, but that there may be little to no difference in mortality in patients not requiring supplemental oxygen at the time of drug initiation [bib_ref] ACTT-1 Study Group Members. Remdesivir for the treatment of Covid-19-final report, Beigel [/bib_ref] [bib_ref] Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial, Wang [/bib_ref]. In consideration of limited treatment options for COVID-19, the SMPC considered the evidence as insufficient to advise against considering the use of remdesivir in patients who do not require supplemental oxygen at the time of drug initiation. Further research is needed on treatment effects by oxygenation status at baseline.
Hence, our past conclusions are unchanged; in patients not requiring invasive mechanical ventilation or ECMO at the time of drug initiation, a 5-day course of remdesivir may be superior to a 10-day course for the following outcomes, with no evidence of increased harm with the shorter duration: mortality (slight reduction), recovery (modest increase), time to recovery (slight reduction), clinical improvement (modest increase), and the proportion of patients on invasive mechanical ventilation or ECMO at follow-up (slight reduction).

## Practice point 2: consider extending the use of remdesivir to 10 days to treat hospitalized patients with covid-19 who require mechanical ventilation or ecmo within a 5-day course

## Updated rationale
The previous version of the practice points concluded that evidence suggests a reduction in mortality with extension of remdesivir treatment to 10 days that outweighs potential harms among patients with COVID-19 who progress to requiring mechanical ventilation or ECMO by day 5 . This conclusion was based on evidence suggesting a net benefit for a 10-day course of remdesivir in these patients compared with placebo or standard care and on a post hoc analysis considering ECMO = extracorporeal membrane oxygenation. * Measured as absolute risk difference (when not otherwise specified).  Described as "slight increase or decrease."  Described as "modest increase or decrease."  Described as "large increase or decrease." . Evidence Gaps
Additional studies are needed to assess the optimal treatment duration with remdesivir (i.e., 5-d vs. 10-d course) and to determine if there is variation in the optimal duration of treatment with remdesivir across different subgroups of patients. Additional studies are needed to assess if the effectiveness of remdesivir treatment for COVID-19 varies by severity (e.g., respiratory support requirements) of COVID-19. There is a need for studies assessing whether remdesivir treatment outcomes vary by symptom duration in patients with COVID-19. NEW: Studies are needed to determine the effectiveness of extending an initial 5-d course of remdesivir to 10 d and to identify subpopulations of patients with COVID-19 who may benefit from longer treatment. Future studies should consider evaluating additional critical and important clinical outcomes, such as respiratory failure or duration of mechanical ventilation. variation in disease severity (respiratory support requirements) when comparing a 5-day course with a 10-day course of remdesivir. The post hoc analysis found that treatment beyond 5 days did not improve mortality among patients who were receiving noninvasive positivepressure ventilation or high-or low-flow oxygen or who were breathing ambient air; however, among patients with COVID-19 who progressed to requiring mechanical ventilation or ECMO at day 5, continued treatment through 10 days resulted in lower mortality. The updated evidence report now rates the post hoc analysis (previously not rated) as insufficient, but the direction of effect still suggests potential benefit (based on this post hoc analysis and the overall findings for a 10day course versus placebo or standard care). The SMPC also considered that currently, with limited availability of other effective treatments to manage hospitalized patients with COVID-19, extending treatment to 10 days is a consideration, particularly for patients who have not demonstrated any adverse effect profile while receiving the 5-day course.

## Clinical guideline

## Practice point 3: avoid initiating remdesivir to treat hospitalized patients with covid-19 who are already on mechanical ventilation or ecmo

## New rationale
Our current understanding of COVID-19 progression is that patients who are admitted on mechanical ventilation or ECMO have likely progressed beyond the viral stage of the illness to the inflammatory stage and are less likely to improve from antivirals; hence, it is important to avoid any additional toxicity from remdesivir, unless there is evidence for potential benefit. This understanding is consistent with findings from a newly reported pooled subgroup analysis of 3 studies comparing a 10day course of remdesivir versus placebo or standard care, which showed that remdesivir may result in a modest increase in mortality in patients receiving mechanical ventilation or ECMO at the time of drug initiation [bib_ref] ACTT-1 Study Group Members. Remdesivir for the treatment of Covid-19-final report, Beigel [/bib_ref] [bib_ref] Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial, Wang [/bib_ref]. This is also consistent with previously reported post hoc findings from 1 study that showed no improvement in time to recovery with a 10-day course among patients receiving invasive mechanical ventilation or ECMO at baseline [bib_ref] ACTT-1 Study Group Members. Remdesivir for the treatment of Covid-19-final report, Beigel [/bib_ref]. Studies evaluating the effectiveness of a 5day course have not investigated the effect of baseline COVID-19 severity.
Although the evidence base is limited, the SMPC considers these findings a signal that the potential harms of remdesivir may outweigh the potential benefits in patients who are receiving invasive mechanical ventilation or ECMO at baseline and cautions against initiating remdesivir treatment in these patients. Note: The practice points are developed by the SMPC of the ACP. The practice points are guides only and may not apply to all patients and all clinical situations. All practice points are considered automatically withdrawn or invalid 5 years after publication, or once an update has been issued.
Financial Support: Financial support for the development of the Practice Points comes exclusively from the ACP operating budget.
Disclosures: All financial and intellectual disclosures of interest were declared and potential conflicts were discussed and managed. Dr. Obley participated in discussion of the practice points but was recused from authorship and voting due to a moderate-level conflict of interest (author of supporting systematic review). Drs. Kansagara and Marcucci participated in the discussion but were recused from authorship and voting due to moderate-level conflicts of interest (authors of recent relevant systematic reviews). A record of disclosures of interest and management of conflicts is kept for each SMPC meeting and conference call and can be viewed at www.acponline.org/about-acp /who-we-are/leadership/boards-committees-councils/scientific -medical-policy-committee/disclosure-of-interests-and-conflict -of-interest-management-summary-for-scientific-medical-policy. Disclosures can also be viewed at www.acponline.org/authors /icmje/ConflictOfInterestForms.do?msNum=M20-8101.

## Appendix: overview of practice points development process and methods

## Practice points development process
The SMPC, in collaboration with staff from ACP's Department of Clinical Policy, developed these practice points on the basis of a rapid and living systematic evidence review done by the VA Evidence Synthesis Program in Minneapolis, Minnesota . The SMPC comprises 11 internal medicine physicians representing various clinical areas of expertise and 1 public (nonclinician) member and includes members with expertise in epidemiology, evidence synthesis, healthy policy, and guideline development. In addition to contributing clinical, scientific, and methodological expertise, Clinical Policy staff provided administrative support and liaised among the SMPC, the evidence review funding entity and evidence team, and the journal. Clinical Policy staff and the SMPC reviewed and prioritized potential topic suggestions from ACP members, SMPC members, and ACP governance. A committee subgroup, including the SMPC chair, worked with staff to draft the key questions and led the development of the practice points. Clinical Policy staff worked with the subgroup and an independent evidence review team to refine the key questions and determine appropriate evidence synthesis methods for each key question. Via conference calls and e-mail, Clinical Policy staff worked with the committee subgroup to draft the practice points on the basis of the results of the rapid and living systematic evidence review. The full SMPC reviewed and approved the final practice points. Before journal submission, ACP's Executive Committee of the Board of Regents also reviewed and approved the practice points on behalf of the ACP Board of Regents. The evidence review team will continually update the evidence review. ACP will update the practice points based on the evidence review using the same process as the first version described above. Updates are currently planned for every 2 months through December 2021. The SMPC will continuously assess the priority of the topic and the overall state of evidence, including the anticipated rate of new evidence, and may choose to modify the update intervals accordingly (any modifications will be described in an Update Alert).

## Methodological differences from the who guideline
On 20 November 2020, the WHO published an update of its "Therapeutics and COVID-19: Living Guideline". In this guideline, the WHO "suggests against administering remdesivir in addition to standard care, in hospitalized patients with COVID-19, regardless of disease severity" (conditional recommendation). A review of current, publicly available documents [bib_ref] World Health Organization. Summary: what is this living guideline, Siemieniuk [/bib_ref] showed that there are 3 important methodological differences between the WHO guideline and the ACP practice points that may contribute to differing conclusions between ACP and WHO.
The WHO guideline is based on a network meta-analysis comparing multiple drug treatments. The ACP practice points were developed on the basis of a VA Evidence Synthesis Program living systematic evidence review with the sole focus of evaluating the benefits and harms of remdesivir in hospitalized patients [bib_ref] Major update: remdesivir for adults with COVID-19. A living systematic review and..., Kaka [/bib_ref].
The WHO guideline considered the effect of remdesivir regardless of its duration of use, whereas the ACP practice points focused specifically on the effectiveness and comparative effectiveness of differing durations of remdesivir use-5 days and 10 days compared with placebo or standard care or the other duration.
The WHO guideline did not make a recommendation based on disease severity. WHO requested subgroup analyses from its network meta-analysis team and judged the credibility to be insufficient when assessing the variation in effectiveness of remdesivir by disease severity (WHO severity classifications). ACP provides clinical advice based on disease severity (baseline oxygen requirements). ACP considered subgroup analyses reported within the individual studies and those done de novo by the authors of the supporting rapid, living systematic review [bib_ref] Major update: remdesivir for adults with COVID-19. A living systematic review and..., Kaka [/bib_ref].
[fig] 19: = coronavirus disease 2019; FDA = U.S. Food and Drug Administration; IV = intravenous; VA = U.S. Department of Veterans Affairs. Annals.org Annals of Internal Medicine  ol. 174 No. 5  May 2021 5 [/fig]
[fig] From: American College of Physicians, Philadelphia, Pennsylvania (A.Q., I.E.); American College of Physicians, Philadelphia, and Villanova University, Villanova, Pennsylvania (J.Y.); University of Massachusetts Medical School and Saint Vincent Hospital, Worcester, Massachusetts (G.M.A.); University of Illinois College of Medicine at Urbana-Champaign, Champaign, Illinois (J.A.J.); Penn Medicine, Philadelphia, Pennsylvania (M.A.F., M.C.M.); and Portland Veterans Affairs Medical Center and Oregon Health & Science University, Portland, Oregon (L.L.H.). [/fig]
[table] Table 1: Practice Points (Version 2) [/table]
[table] Table 2: Updated Evidence Summary for the Use of Remdesivir as Treatment for Patients With COVID-19: What Information Does the Evidence Provide? [/table]
[table] Table 4: Thresholds for Determining Magnitude of Effect* [/table]