key: cord-0295231-wivze3qs
authors: Huang, D. T.; McCreary, E. K.; Bariola, J. R.; Minnier, T. E.; Wadas, R. J.; Shovel, J. A.; Albin, D.; Marroquin, O. C.; Kip, K. E.; Collins, K.; Schmidhofer, M.; Wisniewski, M. K.; Nace, D. A.; Sullivan, C.; Axe, M.; Meyers, R.; Weissman, A.; Garrard, W.; Peck-Palmer, O. M.; Wells, A.; Bart, R. D.; Yang, A.; Berry, L. R.; Berry, S.; Crawford, A. M.; McGlothlin, A.; Khadem, T.; Linstrum, K.; Montgomery, S. K.; Ricketts, D.; Kennedy, J. N.; Pidro, C. J.; Zapf, R. L.; Kip, P. L.; Haidar, G.; Snyder, G. M.; McVerry, B. J.; Yealy, D. M.; Angus, D. C.; Seymour, C. W.
title: Effectiveness of casirivimab and imdevimab, and sotrovimab during Delta variant surge: a prospective cohort study and comparative effectiveness randomized trial
date: 2021-12-30
journal: nan
DOI: 10.1101/2021.12.23.21268244
sha: 87f1e4802447094e32ac6d67f0486a9f4dfa33c3
doc_id: 295231
cord_uid: wivze3qs

IMPORTANCEThe effectiveness of monoclonal antibodies (mAbs), casirivimab and imdevimab, and sotrovimab, for patients with mild to moderate COVID-19 from the Delta variant is unknown. OBJECTIVETo evaluate the effectiveness of mAbs for the Delta variant compared to no treatment, and the comparative effectiveness between mAbs. DESIGN, SETTING, AND PARTICIPANTSTwo parallel studies among patients who met Emergency Use Authorization criteria for mAbs from July 14, 2021 to September 29, 2021: i.) prospective observational cohort study comparing mAb treatment to no mAb treatment and, ii.) Bayesian adaptive randomized trial comparing the effectiveness of casirivimab-imdevimab versus sotrovimab. In the observational study, we compared eligible patients who received mAb at an outpatient infusion center at UPMC, to nontreated patients with a positive SARS-CoV-2 test. In the comparative effectiveness trial, we randomly allocated casirivimab-imdevimab or sotrovimab to patients presenting to infusion centers and emergency departments, per system therapeutic interchange policy. EXPOSUREIntravenous mAb per their EUA criteria. MAIN OUTCOMES AND MEASURESFor the observational study, risk ratio estimates for hospitalization or death by 28 days were compared between mAb treatment to no mAb treatment using propensity matched models. For the comparative effectiveness trial, the primary outcome was hospital-free days (days alive and free of hospital) within 28 days, where patients who died were assigned -1 day) in a Bayesian cumulative logistic model, adjusted for treatment location, age, sex, and time. Inferiority was defined as a 99% posterior probability of an odds ratio <1. Equivalence was defined as a 95% posterior probability that the odds ratio is within a given bound. RESULTSAmong 3,558 patients receiving mAb, the mean age was 54 (SD 18 years), 1,511 (43%) were treated in an infusion center, and 450 (13%) were hospitalized or died by day 28. In propensity matched models, mAb treatment was associated with reduced risk of hospitalization or death compared to no treatment (risk ratio (RR)=0.40, 95% CI: 0.28-0.57). Both casirivimab and imdevimab (RR=0.31, 95% CI: 0.20-0.50), and sotrovimab (RR=0.60, 95% CI: 0.37-1.00) reduced hospitalization or death compared to no mAb treatment. Among patients allocated randomly to casirivimab and imdevimab (n=2,454) or sotrovimab (n=1,104), the median hospital-free days were 28 (IQR 28-28) for both groups, 28-day mortality was 0.5% (n=12) and 0.6% (n=7), and hospitalization by day 28 was 12% (n=291) and 12% (n=140), respectively. Compared to casirivimab and imdevimab, the median adjusted odds ratio for hospital-free days was 0.88 (95% credible interval, 0.70-1.11) for sotrovimab. This odds ratio yielded 86% probability of inferiority of sotrovimab versus casirivimab and imdevimab, and 79% probability of equivalence. CONCLUSIONS AND RELEVANCEIn non-hospitalized patients with mild to moderate COVID-19 due to the Delta variant, casirivimab and imdevimab and sotrovimab were both associated with a reduced risk of hospitalization or death. The comparative effectiveness of mAbs appeared similar, though prespecified criteria for statistical inferiority or equivalence were not met. TRIAL REGISTRATIONClinicalTrials.gov: NCT04790786 Key PointsO_ST_ABSQuestionC_ST_ABSIn non-hospitalized patients with mild to moderate COVID-19 due to the Delta variant, what is the effectiveness of monoclonal antibodies (mAb) compared to no treatment, and what is the comparative effectiveness between mAb? FindingsAmong 3,069 patients, mAb treatment (casirivimab and imdevimab or sotrovimab) was associated with reduced risk of hospitalization or death by 28 days compared to no treatment (risk ratio=0.40, 95% CI: 0.28-0.57). In a Bayesian randomized comparative effectiveness trial of casirivimab and imdevimab vs. sotrovimab in 3,558 patients, the median hospital-free days were 28 days for both groups. Compared to casirivimab-imdevimab, the median adjusted odds ratio for hospital-free days was 0.88 (95% credible interval, 0.70-1.11) for sotrovimab, an 86% probability of inferiority of sotrovimab versus casirivimab and imdevimab, and 79% probability of equivalence. MeaningIn non-hospitalized patients with mild to moderate COVID-19 due to the Delta variant, casirivimab and imdevimab and sotrovimab were associated with reduced risk of hospitalization or death compared to no treatment. The comparative effectiveness of mAbs appeared similar, though prespecified criteria for statistical inferiority or equivalence were not met.

Monoclonal antibodies (mAbs) were granted U.S. Food and Drug Administration (FDA) Emergency Use Authorization (EUA) for treatment of mild to moderate COVID-19. 1, 2 However, their effectiveness with the Delta variant is unknown.

In February 2021, UPMC partnered with the U.S. Federal COVID-19 Response Team and received bamlanivimab, bamlanivimab-etesevimab, and casirivimab-imdevimab to expand clinical use and evaluate their effectiveness using a learning health system approach. This approach embeds knowledge generation into daily practice to seek continuous improvement in care. 3, 4, 5 In April 2021, the EUA for bamlanivimab was revoked, and in June 2021, UPMC partnered with GlaxoSmithKline and Vir Biotechnology to make sotrovimab available to EUA-eligible patients and evaluate its effectiveness.

Because the U.S. government paused distribution of bamlanivimab-etesevimab, and the Delta variant became dominant in the U.S in summer 2021, we evaluated the effectiveness of casirivimab-imdevimab and sotrovimab from July 2021 to September 2021. 6, 7 This report presents an evaluation of casirivimab-imdevimab and sotrovimab from July 14, 2021 to September 29, 2021, with results released due to the Delta variant public health crisis. This study sought to determine, i) the effectiveness of mAbs for the Delta variant compared to no treatment, and ii) the comparative effectiveness between mAbs.

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This report includes two studies: i) a propensity score matched observational study of mAb treatment versus no mAb treatment (UPMC Quality Improvement Review Committee Project ID 2882 and Project ID 3116), and ii) a randomized comparative effectiveness trial of casirivimab and imdevimab versus sotrovimab (UPMC Quality Improvement Committee Project ID 3280 and University of Pittsburgh Institutional Review Board (IRB) STUDY21020179).

UPMC is a 40-hospital integrated health system principally in central and western Pennsylvania. After an EUA was granted for bamlanivimab on November 9, 2020, 8 UPMC developed a mAb treatment infrastructure. 9 , 10 On November 21, 2020, the UPMC Pharmacy and Therapeutics Committee wrote a therapeutic interchange policy in response to the issuance of an EUA for casirivimab and imdevimab and unpredictable mAb supply. The policy considered all available mAbs equivalent; a patient could receive any mAb based on local inventory. The policy was updated to include sotrovimab on July 9, 2021. All pharmacies supplying all infusion sites had equal opportunity to order any available mAb from a central supply facility. Prescribers were required to provide and review all mAb EUA Fact Sheets with the patient at time of referral and explain the patient could receive any EUA-governed mAb under the therapeutic interchange policy. EUA-eligible patients were referred via the electronic medical record (EMR) systems for UPMC providers and by paper order for non-UPMC prescribers. A centralized team with nurses, administrators, pharmacists, and physicians reviewed orders daily to confirm criteria for receipt. Decentralized nursing teams then contacted and scheduled eligible patients for infusions. All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. We used the EMR to access all key clinical data including detailed sociodemographic and medical history data, and hospitalization after mAb treatment, and augmented by manual review and data collection.

We linked the deidentified primary data sources using common variables within the UPMC data systems aggregated in its Clinical Data Warehouse. We conducted Social Security Administration Death Master File queries for vital status. 11

Both mAb were provided as per their EUAs and were provided intravenously for all patients in this report. Patients who received casirivimab and imdevimab via subcutaneous injection were excluded from the analysis.

The study population was derived from patients who received mAb treatment at UPMC infusion centers from July 14, 2021 to September 29, 2021. We derived a comparator group from the same at-risk population by identifying non-hospitalized patients with a positive polymerase chain reaction or antigen test for SARS-CoV-2 during the same time period who were eligible for mAb treatment based on EUA criteria but were not treated. For treated patients, the follow-up period began the day of treatment. For comparator patients, the follow-up period began one day after their SARS-CoV-2 test result date, which corresponded to the earliest time from test positivity to mAb treatment for treated patients. We All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this this version posted December 27, 2021. ; https://doi.org/10.1101/2021.12.23.21268244 doi: medRxiv preprint conducted the analysis on patients treated at infusion centers, as it was not possible to identify a comparator group for patients treated in EDs.

The primary outcome was hospitalization or death by 28 days. Secondary outcomes included the 28-day rate of hospitalization, ICU admission, mechanical ventilation, and mortality.

We performed three analyses. We used propensity matching to compared mAb-eligible patients to, i) all mAb treated patients, ii.) casirivimab and imdevimab treated patients, and iii.) sotrovimab treated patients, respectively. Propensity scores were derived from multivariable logistic regression models fit from variables with mAb treatment as the response variable and forward stepwise selection of pretreatment explanatory variables at p < 0.15. We included variables deemed biologically relevant (e.g., age) prior to stepwise selection. We used a matching ratio (treated/untreated) of 1:2 with a maximum propensity score probability difference of 0.01. We compared characteristics of treated versus nontreated patients using Student t tests for continuous variables and χ 2 tests for categorical variables, prior to and after matching by propensity score. The primary outcome analysis consisted of the 1:2 matched comparisons of treated patients to non-treated control patients, with study outcomes expressed as an effect estimate of treatment (risk ratio, 95% confidence interval). Because of the similarity of casirivimab and imdevimab and sotrovimab treated patients (including nearly identical distributions of propensity scores), and to insure the same reference group (untreated patients) for comparison, the full set of matched controls was used in all analyses. All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 

The Bayesian adaptive platform trial provided the mAb therapeutic interchange via random allocation.

The UPMC Quality Improvement Committee approved the study, including the random therapeutic interchange. The University of Pittsburgh IRB considered the randomized therapeutic interchange to be quality improvement and approved the additional data collection and analyses. A custom application built into the EMR linked local inventory to patient encounters and provided a random mAb allocation at time of mAb referral. Patients provided verbal consent to receive mAb therapy as part of routine care within the EUA. The prescriber and/or patient could request a specific mAb if desired.

The primary analysis population was the "as-infused" population of all patients allocated to sotrovimab or casirivimab and imdevimab, and who received mAb treatment at UPMC infusion centers and EDs during the study period. As all arms included mAb, there was no anticipated relationship between lack of infusion and the assigned arm. Due to episodic mAb shortages, some patients were treated at sites with only one available mAb at the time of treatment. We included these patients in the primary analysis as prescribing physicians and patients were blinded to drug availability at time of randomization and patients could be treated at a site different than the randomization site, pending scheduling availability.

All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The primary outcome was hospital-free days up to day 28 after mAb treatment. This outcome is an ordinal endpoint with death as the worst outcome (labeled -1), then the length of time alive and free of hospitalization, such that the best outcome would be 28 hospital-free days. If a patient had intervening days free of hospital and was then re-hospitalized, the patient was given credit for the intervening days as free of the hospital. The secondary outcome was mortality at 28 days. We evaluated outcomes stratified by infusion location (ED versus infusion center), and the frequency of adverse events. We assessed SARS-CoV-2 variant prevalence in a random subset of enrolled patients and in our Pennsylvania catchment using Global Initiative on Sharing All Influenza Data (GISAID). 7

The trial statistical analysis plan was written by blinded investigators prior to data lock and analysis. The platform is designed to continuously evaluate multiple mAb, with randomization continuing until pre- The primary model was a Bayesian cumulative logistic model that adjusted for treatment location (infusion center or ED), age (<30, 30-39, 40-49, 50-59, 60-69, 70-79, and ≥80 years), sex, and time (2-All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. week epochs). The comparison between individual mAbs were based on the relative odds ratio between a given two arms for the ordinal primary outcome. An odds ratio for an arm to a comparator greater than 1 implies improved outcomes on the ordinal scale. A sliding scale with different levels of equivalence bounds was pre-defined. Equivalence between two arms was defined as a 95% posterior probability that the odds ratio is within a given odds ratio bound. Inferiority of one arm compared to another was defined as a 99% posterior probability of an odds ratio less than 1.

We conducted a sensitivity analysis that excluded patients who received a mAb infusion at a site with only one available mAb treatment option in their "as infused" group. We conducted a priori subgroup analyses by vaccine status (full, partial, unvaccinated, unknown), symptom onset (>5 days, <5 days), and location (infusion center, ED).

Due to the Delta variant public health crisis, we unblinded and analyzed patients allocated through September 29, 2021, prior to having knowingly met any pre-specified statistical threshold.

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The mean age (SD) of the 1,028 treated patients was 53 (16) years versus 49 (21) years for the 5,171 patients who did not receive mAb (p < .001). Treated patients were less likely than no mAb patients to be of Black race, had lower mean Charlson Comorbidity Index scores, and more likely to have greater body mass index. After propensity score matching, treated and non-mAb treated patients were similar for all variables included in the propensity score model, the distribution of propensity scores, and variables not included in the model (eFigure 2, eTable 1).

Of the 1,023 propensity-matched patients who received mAb at an infusion center, 35 (3%) were hospitalized or died, and of the 2,046 propensity-matched patients who did not receive mAb, 174 (8.5%)

were hospitalized or died. The mortality rate was 2.9% (n=60). In the propensity matched analysis, patients receiving mAb had lower adjusted risk of hospitalization or death (risk ratio 0.40, 95% CI: 0.28-0.57), compared to no mAb treatment. Of the 712 propensity-matched patients who received casirivimab and imdevimab, 19 (2.7%) were hospitalized and one died (0.1%), with lower adjusted risk of hospitalization or death (risk ratio 0.31, 95% CI: 0.20-0.50), compared to no mAb treatment. Of the 311 propensity-matched patients who received sotrovimab, 16 (5.1%) were hospitalized and none died, yielding lower adjusted risk of hospitalization or death (risk ratio 0.60, 95% CI: 0.37-1.00), compared to no mAb treatment. Unmatched analyses had similar results (eTable 2).

All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Among 4 ,530 referred and allocated patients, 3,558 (79%) were infused (casirivimab and imdevimab, n=2454, sotrovimab, n=1104, Figure 1 ). The mean age across groups was 54 years, half were female (54%), 12% were Black, and the most common risk factors were body mass index > 25, age > 65 years, and hypertension. Mean duration of symptom onset to infusion was 5.9 days. Of those allocated to a mAb but excluded (N=972), most were not infused due to declining treatment or inability to contact (N=437, 45%), undetermined reasons (N=183, 19%), or were scheduled but not infused (N=116, 12%).

One patient requested a specific mAb different than randomized assignment. All patients (N=79) tested for variant type had Delta, consistent with Pennsylvania GSAID data for this time period which showed nearly all cases were Delta (eFigure 1). Baseline characteristics were similar across groups ( Table 2 ).

The median hospital-free days were 28 (IQR 28-28) (Table 3, Figure 2 ). Relative to the casirivimab and imdevimab group, the posterior median adjusted odds ratios from the primary model was 0.88 (95% credible interval, 0.70-1.11) for the sotrovimab group. This odds ratio resulted in an 86% probability of inferiority for sotrovimab versus casirivimab and imdevimab. The probability of equivalence between sotrovimab and casirivimab and imdevimab at the first pre-specified bound was 79%. No comparison met prespecified criteria for statistical inferiority or equivalence.

The 28-day mortality rates were 0.5% (12/2,454) and 0.6% (7/1,104), and hospitalization rates were 11.9% (291/2,454) and 12.7% (140/1,104), in the casirivimab and imdevimab, and sotrovimab groups, All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 

We performed multiple sensitivity analyses to determine the robustness of our results. First, we excluded patients (n=1,162) who received casirivimab and imdevimab at a location where only casirivimab and imdevimab was available and found similar results (81% probability of sotrovimab inferiority to casirivimab and imdevimab, 79% equivalence). No subgroup analysis except location met the pre-specified thresholds for statistical inferiority or equivalence. Among the 1,511 patients treated at an infusion center, the median odds ratio of sotrovimab compared to casirivimab and imdevimab was 0.48 (95% credible interval, 0.28-0.84), resulting in a 99.5% probability of inferiority.

Among the 2,454 patients treated with casirivimab and imdevimab, adverse events (AE) and serious adverse events (SAE) were rare, reported in 17 (0.5%) and 7 (0.2%) of patients, respectively. Similarly, for the 1,104 sotrovimab treated patients, respective rates were 0.5% (6 patients) and 0.4% (4 patients).

The most commonly reported AE were flushing, itching, breathing difficulties, and chest tightness/pain. All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 

During the COVID-19 Delta variant surge, we found that casirivimab-imdevimab and sotrovimab were each associated with a reduced risk-adjusted hospitalization and death among patients with mild to moderate COVID-19 compared to no treatment. In a comparative effectiveness randomized trial, no primary analysis met a prespecified trigger for conclusions of inferiority or equivalence, although the subgroup analysis of patients treated in an infusion center found superiority of casirivimab-imdevimab over sotrovimab.

The Delta variant of SARS-CoV-2 was observed late 2020, and by July 2021 was the dominant strain

worldwide. Yet, early evidence that demonstrated the efficacy of mAb were conducted prior to the emergence of Delta. Our data extend earlier work to show that mAbs are associated with improved outcomes in Delta in a cohort with a robust sample size and methods to adjust for treatment selection and confounding. Future work will determine effectiveness versus the Omicron variant.

We found no difference when comparing the effectiveness of mAb according to predefined statistical thresholds. This finding could be due to true absence of a difference or from insufficient power to detect a difference due to our decision to evaluate early because of pandemic emergency. In an a priori subgroup, we did observe a 99.5% probability of inferiority in patients treated at an infusion center.

Although not a primary analysis, this finding, if replicated, suggests that at least for patients with the Delta variant treated in an infusion center, casirivimab-imdevimab may be preferred. Patients presenting to an ED may have a greater illness severity compared to patients presenting to a scheduled appointment at an infusion center, and their illness severity may be the main determinant of their subsequent course, not mAb type received. All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. There are many limitations to these studies. First, the observational analysis of mAb treatment versus no mAb treatment may be subject to residual or unmeasured confounding. Second, we evaluated comparative effectiveness trial results early due to the Delta variant crisis and the primary analysis was inconclusive. Third, this report is restricted to the patients in the catchment of UPMC, limiting generalizability. Finally, we were not powered to determine treatment effects by symptom onset or vaccine status. All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 

In non-hospitalized patients with mild to moderate COVID-19 due to the Delta variant, casirivimab and imdevimab, and sotrovimab were both associated with reduced risk of hospitalization or death. The comparative effectiveness of mAbs appeared similar, though prespecified criteria for statistical inferiority or equivalence were not met.

All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 

All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this this version posted December 27, 2021. ; https://doi.org/10.1101/2021.12.23.21268244 doi: medRxiv preprint

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Primary outcome is displayed as horizontally stacked proportions by monoclonal antibody type. Red represents worse values and blue represents better values. The median adjusted odds ratio from the primary analysis, using a Bayesian cumulative logistic model, was 0.88 (95% credible interval, 0.70-1.11) for sotrovimab versus casirivimab and imdevimab. This odds ratio yielded 86% probability of inferiority for sotrovimab versus casirivimab and imdevimab, and 79% probability of equivalence between the two at the first pre-specified bound.

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The copyright holder for this this version posted December 27, 2021. 

All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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After propensity score matching, treated and non-mAb treated patients were similar on the distribution of propensity scores.

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Title and abstract 1 How participants were allocated to interventions (e.g., "random allocation," "randomized," or "randomly assigned") preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Method used to implement the random allocation sequence (e.g., numbered containers or central telephone), clarifying whether the sequence was concealed until interventions were assigned 11-12

Randomizationimplementation 10 Who generated the allocation sequence, who enrolled participants, and who assigned participants to their groups __ Blinding (masking) 11 Whether participants, those administering the interventions, and those assessing the outcomes were blinded to group assignment

If blinding was not done, or was not possible, explain why 11 Statistical methods 12 Statistical methods used to compare groups for primary outcomes; methods for additional analyses, such as subgroup analyses and adjusted analyses

Flow of participants through each stage (a diagram is strongly recommended)specifically, for each group, report the numbers of participants randomly assigned, receiving intended treatment, completing the study protocol, and analyzed for the primary outcome; describe deviations from planned study protocol, together with reasons Numbers analyzed 16 Number of participants (denominator) in each group included in each analysis and whether analysis was by "intention-totreat;" state the results in absolute numbers when feasible (e.g., 10/20, not 50%)

Outcomes and estimation 17

For each primary and secondary outcome, a summary of results for each group and the estimated effect size and its precision (e.g., 95% CI)

Ancillary analyses 18 Address multiplicity by reporting any other analyses performed, including subgroup analyses and adjusted analyses, indicating which are prespecified and which are exploratory 15 All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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Fact sheet for health care providers emergency use authorization (EUA) of REGEN-COVTM

Frequently asked questions on the emergency use authorization of sotrovimab

Optimizing the Trade-off Between Learning and Doing in a Pandemic

The Learning Healthcare System: Workshop Summary

A Learning Health System Randomized Trial of Monoclonal Antibodies for COVID-19

Pause in the distribution of bamlanivimab/etesevimab

Global Information Sharing All Influenza Data. Tracking of variants

Fact sheet for health care providers emergency use authorization (EUA) of bamlanivimab

Fusing Randomized Trials With Big Data: The Key to Self-learning Health Care Systems?

The authors thank the clinical staff of the UPMC monoclonal antibody infusion centers as well as the support and administrative staff behind this effort, including but not limited to: Michelle Adam, Jodi