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Casirivimab/imdevimab for COVID-19: real-time meta analysis of 20 studies
Covid Analysis, May 21, 2022, DRAFT
https://c19regn.com/meta.html
0 0.5 1 1.5+ All studies 61% 20 46,179 Improvement, Studies, Patients Relative Risk Mortality 53% 8 32,929 Ventilation -1% 2 9,326 ICU admission 67% 2 9,810 Hospitalization 54% 9 38,972 Progression 56% 3 680 Recovery 33% 5 8,277 Cases 80% 4 3,265 Viral clearance 55% 2 1,709 RCTs 61% 9 21,306 RCT mortality 20% 3 15,162 Peer-reviewed 61% 9 29,842 Prophylaxis 93% 3 3,061 Early 58% 14 30,180 Late 33% 3 12,938 Casirivimab/imdevimab for COVID-19 c19regn.com May 2022 Favorscasirivimab/im.. Favorscontrol after exclusions
Statistically significant improvements are seen for mortality, hospitalization, progression, recovery, cases, and viral clearance. 16 studies from 10 independent teams in 4 different countries show statistically significant improvements in isolation (8 for the most serious outcome).
Meta analysis using the most serious outcome reported shows 61% [42‑74%] improvement. Results are similar for Randomized Controlled Trials, similar after exclusions, and similar for peer-reviewed studies. Results are consistent with early treatment being more effective than late treatment.
Results are robust — in exclusion sensitivity analysis 12 of 20 studies must be excluded to avoid finding statistically significant efficacy in pooled analysis.
0 0.5 1 1.5+ All studies 61% 20 46,179 Improvement, Studies, Patients Relative Risk Mortality 53% 8 32,929 Ventilation -1% 2 9,326 ICU admission 67% 2 9,810 Hospitalization 54% 9 38,972 Progression 56% 3 680 Recovery 33% 5 8,277 Cases 80% 4 3,265 Viral clearance 55% 2 1,709 RCTs 61% 9 21,306 RCT mortality 20% 3 15,162 Peer-reviewed 61% 9 29,842 Prophylaxis 93% 3 3,061 Early 58% 14 30,180 Late 33% 3 12,938 Casirivimab/imdevimab for COVID-19 c19regn.com May 2022 Favorscasirivimab/im.. Favorscontrol after exclusions
Efficacy is variant dependent. In Vitro studies suggest a lack of efficacy for omicron [Liu, Sheward, Tatham, VanBlargan]. Monoclonal antibody use with variants can be associated with prolonged viral loads, clinical deterioration, and immune escape [Choudhary].
While many treatments have some level of efficacy, they do not replace vaccines and other measures to avoid infection. Only 30% of casirivimab/imdevimab studies show zero events in the treatment arm. Multiple treatments are typically used in combination, and other treatments may be more effective.
No treatment, vaccine, or intervention is 100% available and effective for all variants. All practical, effective, and safe means should be used. Denying the efficacy of treatments increases mortality, morbidity, collateral damage, and endemic risk.
All data to reproduce this paper and sources are in the appendix.
Highlights
Casirivimab/imdevimab reduces risk for COVID-19 with very high confidence for hospitalization, progression, recovery, cases, and in pooled analysis, high confidence for mortality and viral clearance, and very low confidence for ICU admission. Efficacy is variant dependent. Unlikely to be effective for omicron.
We show traditional outcome specific analyses and combined evidence from all studies, incorporating treatment delay, a primary confounding factor in COVID-19 studies.
Real-time updates and corrections, transparent analysis with all results in the same format, consistent protocol for 42 treatments.
A
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Regeneron (RCT) 38% 0.62 [0.29-1.33] recov. time 92 (n) 91 (n) Improvement, RR [CI] Treatment Control Regeneron (RCT) 71% 0.29 [0.17-0.48] death/hosp. 18/1,355 62/1,341 Weinreich (RCT) 50% 0.50 [0.09-2.72] death 2/2,091 4/2,089 Webb 98% 0.02 [0.00-0.27] death 0/115 57/5,536 Cooper 77% 0.23 [0.03-1.65] death 1/1,148 33/8,534 Kakinoki 58% 0.42 [0.17-0.92] progression 13/55 22/53 Komagamine 77% 0.23 [0.01-4.63] ventilation 0/53 2/75 Suzuki (PSM) -200% 3.00 [0.12-73.3] death 1/222 0/222 O'Brien (DB RCT) 85% 0.15 [0.01-2.78] hosp. 0/100 3/104 Shopen -46% 1.46 [0.73-2.67] severe case 24/116 26/243 Osugi 24% 0.76 [0.23-2.49] hosp. 4/30 15/74 Wei 61% 0.39 [0.26-0.60] death/hosp. 23/1,116 27/5,291 Wilden 82% 0.18 [0.05-0.50] hosp. n/a n/a Faraone 92% 0.08 [0.00-1.24] death 0/11 8/23 Tau​2 = 0.39, I​2 = 64.5%, p = 0.00038 Early treatment 58% 0.42 [0.26-0.67] 86/6,504 259/23,676 58% improvement Horby (RCT) 6% 0.94 [0.86-1.02] death 943/4,839 1,029/4,946 Improvement, RR [CI] Treatment Control Somersa.. (DB RCT) 36% 0.64 [0.44-0.93] death 59/804 45/393 McCreary (PSM) 93% 0.07 [0.01-0.51] death 1/652 29/1,304 Tau​2 = 0.15, I​2 = 80.8%, p = 0.16 Late treatment 33% 0.67 [0.39-1.17] 1,003/6,295 1,103/6,643 33% improvement Regeneron (RCT) 94% 0.06 [0.00-1.10] symp. case 0/186 8/223 Improvement, RR [CI] Treatment Control Regeneron (DB RCT) 92% 0.08 [0.00-1.36] hosp. 0/841 6/842 Isa (DB RCT) 93% 0.07 [0.01-0.28] symp. case 3/729 13/240 Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Prophylaxis 93% 0.07 [0.03-0.21] 3/1,756 27/1,305 93% improvement All studies 61% 0.39 [0.26-0.58] 1,092/14,555 1,389/31,624 61% improvement 20 casirivimab/imdevimab COVID-19 studies c19regn.com May 2022 Tau​2 = 0.39, I​2 = 79.5%, p < 0.0001 Effect extraction pre-specified(most serious outcome, see appendix) Favors casirivimab/im.. Favors control
Figure 1. A. Random effects meta-analysis. This plot shows pooled effects, discussion can be found in the heterogeneity section, and results for specific outcomes can be found in the individual outcome analyses. Effect extraction is pre-specified, using the most serious outcome reported. For details of effect extraction see the appendix. B. Scatter plot showing the distribution of effects reported in studies. C. History of all reported effects (chronological within treatment stages).
Introduction
We analyze all significant studies concerning the use of casirivimab/imdevimab for COVID-19. Search methods, inclusion criteria, effect extraction criteria (more serious outcomes have priority), all individual study data, PRISMA answers, and statistical methods are detailed in Appendix 1. We present random effects meta-analysis results for all studies, for studies within each treatment stage, for individual outcomes, for peer-reviewed studies, for Randomized Controlled Trials (RCTs), and after exclusions.
Figure 2 shows stages of possible treatment for COVID-19. Prophylaxis refers to regularly taking medication before becoming sick, in order to prevent or minimize infection. Early Treatment refers to treatment immediately or soon after symptoms appear, while Late Treatment refers to more delayed treatment.
Figure 2. Treatment stages.
Variant Dependence
Efficacy is variant dependent, for example in vitro studies suggest that casirivimab/imdevimab is not effective for the omicron variant [Liu, Sheward, Tatham, VanBlargan, Zhou].
Results
Figure 3 shows a visual overview of the results, with details in Table 1 and Table 2. Figure 4, 5, 6, 7, 8, 9, 10, 11, 12, and 13 show forest plots for a random effects meta-analysis of all studies with pooled effects, mortality results, ventilation, ICU admission, hospitalization, progression, recovery, cases, viral clearance, and peer reviewed studies.
0 0.5 1 1.5+ ALL STUDIES MORTALITY VENTILATION ICU ADMISSION HOSPITALIZATION PROGRESSION RECOVERY CASES VIRAL CLEARANCE RANDOMIZED CONTROLLED TRIALS RCT MORTALITY PEER-REVIEWED After Exclusions ALL STUDIES All Prophylaxis Early Late Casirivimab/imdevimab for COVID-19 C19REGN.COM MAY 2022
Figure 3. Overview of results.
Treatment timeNumber of studies reporting positive effects Total number of studiesPercentage of studies reporting positive effects Random effects meta-analysis results
Early treatment 12 14 85.7% 58% improvement
RR 0.42 [0.26‑0.67]
p = 0.00038
Late treatment 3 3 100% 33% improvement
RR 0.67 [0.39‑1.17]
p = 0.16
Prophylaxis 3 3 100% 93% improvement
RR 0.07 [0.03‑0.21]
p < 0.0001
All studies 18 20 90.0% 61% improvement
RR 0.39 [0.26‑0.58]
p < 0.0001
Table 1. Results by treatment stage.
Studies Early treatment Late treatment Prophylaxis PatientsAuthors
All studies 2058% [33‑74%]33% [-17‑61%]93% [79‑97%] 46,179 339
With exclusions 1957% [30‑74%]33% [-17‑61%]93% [79‑97%] 36,497 330
Peer-reviewed 967% [41‑81%]6% [-2‑14%] 29,842 166
Randomized Controlled TrialsRCTs 963% [42‑76%]19% [-17‑44%]93% [79‑97%] 21,306 175
Table 2. Results by treatment stage for all studies and with different exclusions.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Regeneron (RCT) 38% 0.62 [0.29-1.33] recov. time 92 (n) 91 (n) Improvement, RR [CI] Treatment Control Regeneron (RCT) 71% 0.29 [0.17-0.48] death/hosp. 18/1,355 62/1,341 Weinreich (RCT) 50% 0.50 [0.09-2.72] death 2/2,091 4/2,089 Webb 98% 0.02 [0.00-0.27] death 0/115 57/5,536 Cooper 77% 0.23 [0.03-1.65] death 1/1,148 33/8,534 Kakinoki 58% 0.42 [0.17-0.92] progression 13/55 22/53 Komagamine 77% 0.23 [0.01-4.63] ventilation 0/53 2/75 Suzuki (PSM) -200% 3.00 [0.12-73.3] death 1/222 0/222 O'Brien (DB RCT) 85% 0.15 [0.01-2.78] hosp. 0/100 3/104 Shopen -46% 1.46 [0.73-2.67] severe case 24/116 26/243 Osugi 24% 0.76 [0.23-2.49] hosp. 4/30 15/74 Wei 61% 0.39 [0.26-0.60] death/hosp. 23/1,116 27/5,291 Wilden 82% 0.18 [0.05-0.50] hosp. n/a n/a Faraone 92% 0.08 [0.00-1.24] death 0/11 8/23 Tau​2 = 0.39, I​2 = 64.5%, p = 0.00038 Early treatment 58% 0.42 [0.26-0.67] 86/6,504 259/23,676 58% improvement Horby (RCT) 6% 0.94 [0.86-1.02] death 943/4,839 1,029/4,946 Improvement, RR [CI] Treatment Control Somersa.. (DB RCT) 36% 0.64 [0.44-0.93] death 59/804 45/393 McCreary (PSM) 93% 0.07 [0.01-0.51] death 1/652 29/1,304 Tau​2 = 0.15, I​2 = 80.8%, p = 0.16 Late treatment 33% 0.67 [0.39-1.17] 1,003/6,295 1,103/6,643 33% improvement Regeneron (RCT) 94% 0.06 [0.00-1.10] symp. case 0/186 8/223 Improvement, RR [CI] Treatment Control Regeneron (DB RCT) 92% 0.08 [0.00-1.36] hosp. 0/841 6/842 Isa (DB RCT) 93% 0.07 [0.01-0.28] symp. case 3/729 13/240 Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Prophylaxis 93% 0.07 [0.03-0.21] 3/1,756 27/1,305 93% improvement All studies 61% 0.39 [0.26-0.58] 1,092/14,555 1,389/31,624 61% improvement 20 casirivimab/imdevimab COVID-19 studies c19regn.com May 2022 Tau​2 = 0.39, I​2 = 79.5%, p < 0.0001 Effect extraction pre-specified(most serious outcome, see appendix) Favors casirivimab/im.. Favors control
Figure 4. Random effects meta-analysis for all studies with pooled effects. This plot shows pooled effects, discussion can be found in the heterogeneity section, and results for specific outcomes can be found in the individual outcome analyses. Effect extraction is pre-specified, using the most serious outcome reported. For details of effect extraction see the appendix.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Weinreich (RCT) 50% 0.50 [0.09-2.72] 2/2,091 4/2,089 Improvement, RR [CI] Treatment Control Webb 98% 0.02 [0.00-0.27] 0/115 57/5,536 Cooper 77% 0.23 [0.03-1.65] 1/1,148 33/8,534 Suzuki (PSM) -200% 3.00 [0.12-73.3] 1/222 0/222 Faraone 92% 0.08 [0.00-1.24] 0/11 8/23 Tau​2 = 1.18, I​2 = 44.9%, p = 0.037 Early treatment 78% 0.22 [0.05-0.92] 4/3,587 102/16,404 78% improvement Horby (RCT) 6% 0.94 [0.86-1.02] 943/4,839 1,029/4,946 Improvement, RR [CI] Treatment Control Somersa.. (DB RCT) 36% 0.64 [0.44-0.93] 59/804 45/393 McCreary (PSM) 93% 0.07 [0.01-0.51] 1/652 29/1,304 Tau​2 = 0.15, I​2 = 80.8%, p = 0.16 Late treatment 33% 0.67 [0.39-1.17] 1,003/6,295 1,103/6,643 33% improvement All studies 53% 0.47 [0.26-0.85] 1,007/9,882 1,205/23,047 53% improvement 8 casirivimab/imdevimab COVID-19 mortality results c19regn.com May 2022 Tau​2 = 0.28, I​2 = 71.2%, p = 0.013 Favors casirivimab/im.. Favors control
Figure 5. Random effects meta-analysis for mortality results.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Komagamine 77% 0.23 [0.01-4.63] 0/53 2/75 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.34 Early treatment 77% 0.23 [0.01-4.63] 0/53 2/75 77% improvement Horby (RCT) -1% 1.01 [0.90-1.14] 484/4,556 488/4,642 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.88 Late treatment -1% 1.01 [0.90-1.14] 484/4,556 488/4,642 -1% improvement All studies -1% 1.01 [0.89-1.13] 484/4,609 490/4,717 -1% improvement 2 casirivimab/imdevimab COVID-19 mechanical ventilation results c19regn.com May 2022 Tau​2 = 0.00, I​2 = 0.0%, p = 0.91 Favors casirivimab/im.. Favors control
Figure 6. Random effects meta-analysis for ventilation.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Cooper 48% 0.52 [0.23-1.20] 6/1,148 85/8,534 Improvement, RR [CI] Treatment Control Komagamine 92% 0.08 [0.00-1.32] 0/53 7/75 Tau​2 = 0.70, I​2 = 37.9%, p = 0.18 Early treatment 67% 0.33 [0.07-1.65] 6/1,201 92/8,609 67% improvement All studies 67% 0.33 [0.07-1.65] 6/1,201 92/8,609 67% improvement 2 casirivimab/imdevimab COVID-19 ICU results c19regn.com May 2022 Tau​2 = 0.70, I​2 = 37.9%, p = 0.18 Favors casirivimab/im.. Favors control
Figure 7. Random effects meta-analysis for ICU admission.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Webb 91% 0.09 [0.01-0.63] hosp. 1/115 538/5,536 Improvement, RR [CI] Treatment Control Cooper 52% 0.48 [0.35-0.64] hosp. 45/1,148 703/8,534 Komagamine 29% 0.71 [0.58-0.87] hosp. time 53 (n) 75 (n) O'Brien (DB RCT) 85% 0.15 [0.01-2.78] hosp. 0/100 3/104 Osugi 24% 0.76 [0.23-2.49] hosp. 4/30 15/74 Wei 61% 0.39 [0.30-0.51] hosp. 59/3,280 75/16,284 Wilden 82% 0.18 [0.05-0.50] hosp. n/a n/a Tau​2 = 0.12, I​2 = 68.6%, p < 0.0001 Early treatment 54% 0.46 [0.32-0.66] 109/4,726 1,334/30,607 54% improvement McCreary (PSM) 48% 0.52 [0.33-0.82] hosp. 22/652 85/1,304 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.0053 Late treatment 48% 0.52 [0.33-0.82] 22/652 85/1,304 48% improvement Regeneron (DB RCT) 92% 0.08 [0.00-1.36] hosp. 0/841 6/842 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.08 Prophylaxis 92% 0.08 [0.00-1.36] 0/841 6/842 92% improvement All studies 54% 0.46 [0.34-0.63] 131/6,219 1,425/32,753 54% improvement 9 casirivimab/imdevimab COVID-19 hospitalization results c19regn.com May 2022 Tau​2 = 0.10, I​2 = 61.8%, p < 0.0001 Favors casirivimab/im.. Favors control
Figure 8. Random effects meta-analysis for hospitalization.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Kakinoki 58% 0.42 [0.17-0.92] 13/55 22/53 Improvement, RR [CI] Treatment Control Komagamine 68% 0.32 [0.13-0.68] 8/53 33/75 Suzuki (PSM) 45% 0.55 [0.31-0.96] 17/222 31/222 Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Early treatment 56% 0.44 [0.31-0.62] 38/330 86/350 56% improvement All studies 56% 0.44 [0.31-0.62] 38/330 86/350 56% improvement 3 casirivimab/imdevimab COVID-19 progression results c19regn.com May 2022 Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Favors casirivimab/im.. Favors control
Figure 9. Random effects meta-analysis for progression.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Regeneron (RCT) 38% 0.62 [0.29-1.33] recov. time 92 (n) 91 (n) Improvement, RR [CI] Treatment Control Regeneron (RCT) 29% 0.71 [0.60-0.85] recov. time 1,355 (n) 1,341 (n) Weinreich (RCT) 29% 0.71 [0.58-0.87] recov. time 1,355 (n) 1,341 (n) Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Early treatment 29% 0.71 [0.63-0.81] 0/2,802 0/2,773 29% improvement Somersa.. (DB RCT) 29% 0.71 [0.53-0.96] no disch. 92/804 63/393 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.026 Late treatment 29% 0.71 [0.53-0.96] 92/804 63/393 29% improvement Regeneron (DB RCT) 62% 0.38 [0.23-0.61] recov. time 753 (n) 752 (n) Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.0001 Prophylaxis 62% 0.38 [0.23-0.61] 0/753 0/752 62% improvement All studies 33% 0.67 [0.57-0.79] 92/4,359 63/3,918 33% improvement 5 casirivimab/imdevimab COVID-19 recovery results c19regn.com May 2022 Tau​2 = 0.01, I​2 = 37.0%, p < 0.0001 Favors casirivimab/im.. Favors control
Figure 10. Random effects meta-analysis for recovery.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ O'Brien (DB RCT) 33% 0.67 [0.43-0.98] symp. case 29/100 44/104 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.039 Early treatment 33% 0.67 [0.43-0.98] 29/100 44/104 33% improvement Regeneron (RCT) 94% 0.06 [0.00-1.10] symp. case 0/186 8/223 Improvement, RR [CI] Treatment Control Regeneron (DB RCT) 81% 0.19 [0.12-0.30] cases 20/841 108/842 Isa (DB RCT) 93% 0.07 [0.01-0.28] symp. case 3/729 13/240 Tau​2 = 0.05, I​2 = 11.7%, p < 0.0001 Prophylaxis 85% 0.15 [0.09-0.26] 23/1,756 129/1,305 85% improvement All studies 80% 0.20 [0.07-0.61] 52/1,856 173/1,409 80% improvement 4 casirivimab/imdevimab COVID-19 case results c19regn.com May 2022 Tau​2 = 0.89, I​2 = 88.3%, p = 0.0043 Favors casirivimab/im.. Favors control
Figure 11. Random effects meta-analysis for cases.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ O'Brien (DB RCT) 40% 0.60 [0.45-0.81] viral load 100 (n) 104 (n) Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.001 Early treatment 40% 0.60 [0.45-0.81] 0/100 0/104 40% improvement Regeneron (DB RCT) 69% 0.31 [0.17-0.55] viral time 753 (n) 752 (n) Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Prophylaxis 69% 0.31 [0.17-0.55] 0/753 0/752 69% improvement All studies 55% 0.45 [0.24-0.87] 0/853 0/856 55% improvement 2 casirivimab/imdevimab COVID-19 viral clearance results c19regn.com May 2022 Tau​2 = 0.17, I​2 = 74.9%, p = 0.017 Favors casirivimab/im.. Favors control
Figure 12. Random effects meta-analysis for viral clearance.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Weinreich (RCT) 50% 0.50 [0.09-2.72] death 2/2,091 4/2,089 Improvement, RR [CI] Treatment Control Webb 98% 0.02 [0.00-0.27] death 0/115 57/5,536 Cooper 77% 0.23 [0.03-1.65] death 1/1,148 33/8,534 Kakinoki 58% 0.42 [0.17-0.92] progression 13/55 22/53 Komagamine 77% 0.23 [0.01-4.63] ventilation 0/53 2/75 O'Brien (DB RCT) 85% 0.15 [0.01-2.78] hosp. 0/100 3/104 Osugi 24% 0.76 [0.23-2.49] hosp. 4/30 15/74 Wilden 82% 0.18 [0.05-0.50] hosp. n/a n/a Tau​2 = 0.15, I​2 = 24.2%, p = 0.00017 Early treatment 67% 0.33 [0.19-0.59] 20/3,592 136/16,465 67% improvement Horby (RCT) 6% 0.94 [0.86-1.02] death 943/4,839 1,029/4,946 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.12 Late treatment 6% 0.94 [0.86-1.02] 943/4,839 1,029/4,946 6% improvement All studies 61% 0.39 [0.21-0.75] 963/8,431 1,165/21,411 61% improvement 9 casirivimab/imdevimab COVID-19 peer reviewed trials c19regn.com May 2022 Tau​2 = 0.46, I​2 = 71.2%, p = 0.0044 Effect extraction pre-specified(most serious outcome, see appendix) Favors casirivimab/im.. Favors control
Figure 13. Random effects meta-analysis for peer reviewed studies. [Zeraatkar] analyze 356 COVID-19 trials, finding no significant evidence that peer-reviewed studies are more trustworthy. They also show extremely slow review times during a pandemic. Authors recommend using preprint evidence, with appropriate checks for potential falsified data, which provides higher certainty much earlier. Effect extraction is pre-specified, using the most serious outcome reported, see the appendix for details.
Exclusions
To avoid bias in the selection of studies, we analyze all non-retracted studies. Here we show the results after excluding studies with major issues likely to alter results, non-standard studies, and studies where very minimal detail is currently available. Our bias evaluation is based on analysis of each study and identifying when there is a significant chance that limitations will substantially change the outcome of the study. We believe this can be more valuable than checklist-based approaches such as Cochrane GRADE, which may underemphasize serious issues not captured in the checklists, overemphasize issues unlikely to alter outcomes in specific cases (for example, lack of blinding for an objective mortality outcome, or certain specifics of randomization with a very large effect size), or be easily influenced by potential bias. However, they can also be very high quality.
The studies excluded are as below. Figure 14 shows a forest plot for random effects meta-analysis of all studies after exclusions.
[Cooper], unadjusted results with no group details.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Regeneron (RCT) 38% 0.62 [0.29-1.33] recov. time 92 (n) 91 (n) Improvement, RR [CI] Treatment Control Regeneron (RCT) 71% 0.29 [0.17-0.48] death/hosp. 18/1,355 62/1,341 Weinreich (RCT) 50% 0.50 [0.09-2.72] death 2/2,091 4/2,089 Webb 98% 0.02 [0.00-0.27] death 0/115 57/5,536 Kakinoki 58% 0.42 [0.17-0.92] progression 13/55 22/53 Komagamine 77% 0.23 [0.01-4.63] ventilation 0/53 2/75 Suzuki (PSM) -200% 3.00 [0.12-73.3] death 1/222 0/222 O'Brien (DB RCT) 85% 0.15 [0.01-2.78] hosp. 0/100 3/104 Shopen -46% 1.46 [0.73-2.67] severe case 24/116 26/243 Osugi 24% 0.76 [0.23-2.49] hosp. 4/30 15/74 Wei 61% 0.39 [0.26-0.60] death/hosp. 23/1,116 27/5,291 Wilden 82% 0.18 [0.05-0.50] hosp. n/a n/a Faraone 92% 0.08 [0.00-1.24] death 0/11 8/23 Tau​2 = 0.41, I​2 = 66.7%, p = 0.00082 Early treatment 57% 0.43 [0.26-0.70] 85/5,356 226/15,142 57% improvement Horby (RCT) 6% 0.94 [0.86-1.02] death 943/4,839 1,029/4,946 Improvement, RR [CI] Treatment Control Somersa.. (DB RCT) 36% 0.64 [0.44-0.93] death 59/804 45/393 McCreary (PSM) 93% 0.07 [0.01-0.51] death 1/652 29/1,304 Tau​2 = 0.15, I​2 = 80.8%, p = 0.16 Late treatment 33% 0.67 [0.39-1.17] 1,003/6,295 1,103/6,643 33% improvement Regeneron (RCT) 94% 0.06 [0.00-1.10] symp. case 0/186 8/223 Improvement, RR [CI] Treatment Control Regeneron (DB RCT) 92% 0.08 [0.00-1.36] hosp. 0/841 6/842 Isa (DB RCT) 93% 0.07 [0.01-0.28] symp. case 3/729 13/240 Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Prophylaxis 93% 0.07 [0.03-0.21] 3/1,756 27/1,305 93% improvement All studies 60% 0.40 [0.27-0.59] 1,091/13,407 1,356/23,090 60% improvement 19 casirivimab/imdevimab COVID-19 studies after exclusions c19regn.com May 2022 Tau​2 = 0.39, I​2 = 80.2%, p < 0.0001 Effect extraction pre-specified(most serious outcome, see appendix) Favors casirivimab/im.. Favors control
Figure 14. Random effects meta-analysis for all studies after exclusions. This plot shows pooled effects, discussion can be found in the heterogeneity section, and results for specific outcomes can be found in the individual outcome analyses. Effect extraction is pre-specified, using the most serious outcome reported. For details of effect extraction see the appendix.
Randomized Controlled Trials (RCTs)
Figure 15 shows the distribution of results for Randomized Controlled Trials and other studies, and a chronological history of results. Figure 16 and 17 show forest plots for a random effects meta-analysis of all Randomized Controlled Trials and RCT mortality results. Table 3 summarizes the results.
Figure 15. The distribution of results for Randomized Controlled Trials and other studies, and a chronological history of results.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Regeneron (RCT) 38% 0.62 [0.29-1.33] recov. time 92 (n) 91 (n) Improvement, RR [CI] Treatment Control Regeneron (RCT) 71% 0.29 [0.17-0.48] death/hosp. 18/1,355 62/1,341 Weinreich (RCT) 50% 0.50 [0.09-2.72] death 2/2,091 4/2,089 O'Brien (DB RCT) 85% 0.15 [0.01-2.78] hosp. 0/100 3/104 Tau​2 = 0.02, I​2 = 5.8%, p < 0.0001 Early treatment 63% 0.37 [0.24-0.58] 20/3,638 69/3,625 63% improvement Horby (RCT) 6% 0.94 [0.86-1.02] death 943/4,839 1,029/4,946 Improvement, RR [CI] Treatment Control Somersa.. (DB RCT) 36% 0.64 [0.44-0.93] death 59/804 45/393 Tau​2 = 0.05, I​2 = 74.8%, p = 0.26 Late treatment 19% 0.81 [0.56-1.17] 1,002/5,643 1,074/5,339 19% improvement Regeneron (RCT) 94% 0.06 [0.00-1.10] symp. case 0/186 8/223 Improvement, RR [CI] Treatment Control Regeneron (DB RCT) 92% 0.08 [0.00-1.36] hosp. 0/841 6/842 Isa (DB RCT) 93% 0.07 [0.01-0.28] symp. case 3/729 13/240 Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Prophylaxis 93% 0.07 [0.03-0.21]