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Bamlanivimab/etesevimab for COVID-19: real-time meta analysis of 14 studies
Covid Analysis, August 15, 2022, DRAFT
https://c19ly.com/meta.html
0 0.5 1 1.5+ All studies 55% 14 24,423 Improvement, Studies, Patients Relative Risk Mortality 56% 10 22,988 ICU admission 51% 2 12,628 Hospitalization 41% 9 21,880 Progression 66% 2 513 Recovery 11% 2 1,129 Cases 57% 1 965 Viral clearance 50% 2 1,101 RCTs 45% 5 2,784 RCT mortality 58% 2 1,349 Peer-reviewed 56% 11 22,673 Prophylaxis 57% 1 965 Early 69% 8 17,980 Late 29% 5 5,478 Bamlanivimab/etesevimab for COVID-19 c19ly.com Aug 2022 Favorsbamlanivimab/e.. Favorscontrol after exclusions
Statistically significant improvements are seen for mortality, ICU admission, hospitalization, recovery, and cases. 11 studies from 9 independent teams (all from the same country) show statistically significant improvements in isolation (4 for the most serious outcome).
Meta analysis using the most serious outcome reported shows 55% [30‑71%] improvement. Results are similar for Randomized Controlled Trials, similar after exclusions, and similar for peer-reviewed studies. Early treatment is more effective than late treatment.
Results are robust — in exclusion sensitivity analysis 6 of 14 studies must be excluded to avoid finding statistically significant efficacy in pooled analysis.
0 0.5 1 1.5+ All studies 55% 14 24,423 Improvement, Studies, Patients Relative Risk Mortality 56% 10 22,988 ICU admission 51% 2 12,628 Hospitalization 41% 9 21,880 Progression 66% 2 513 Recovery 11% 2 1,129 Cases 57% 1 965 Viral clearance 50% 2 1,101 RCTs 45% 5 2,784 RCT mortality 58% 2 1,349 Peer-reviewed 56% 11 22,673 Prophylaxis 57% 1 965 Early 69% 8 17,980 Late 29% 5 5,478 Bamlanivimab/etesevimab for COVID-19 c19ly.com Aug 2022 Favorsbamlanivimab/e.. Favorscontrol after exclusions
Efficacy is highly variant dependent. In Vitro studies suggest a lack of efficacy for omicron [Liu, Sheward, 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 7% of bamlanivimab/etesevimab 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
Bamlanivimab/etesevimab reduces risk for COVID-19 with very high confidence for hospitalization, recovery, cases, and in pooled analysis, high confidence for mortality and ICU admission, low confidence for viral clearance, and very low confidence for progression. Efficacy is highly 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 43 treatments.
A
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Gottlieb (RCT) 71% 0.29 [0.09-0.96] hosp./ER 4/101 7/52 Improvement, RR [CI] Treatment Control Webb 80% 0.20 [0.03-1.46] death 1/479 57/5,536 Dougan (DB RCT) 95% 0.05 [0.00-0.90] death 0/518 9/517 Cooper 45% 0.55 [0.07-3.99] death 1/473 33/8,534 Rubin 44% 0.56 [0.07-4.33] death 1/191 10/1,066 Delasobera -119% 2.19 [0.23-20.9] death 3/253 1/185 Dale 89% 0.11 [0.02-0.55] death 5/56 9/19 Wilden 51% 0.49 [0.23-1.04] hosp. n/a n/a Tau​2 = 0.31, I​2 = 37.9%, p = 0.00058 Early treatment 69% 0.31 [0.16-0.60] 15/2,071 126/15,909 69% improvement ACTIV-3/T.. (RCT) -100% 2.00 [0.69-5.83] death 9/163 5/151 Improvement, RR [CI] Treatment Control Bariola 67% 0.33 [0.10-1.01] death 4/234 12/234 Ganesh 74% 0.26 [0.05-1.20] death 2/1,789 8/1,832 Chew (RCT) 25% 0.75 [0.26-2.10] hosp. 6/159 8/158 Priest (PSM) 0% 1.00 [0.33-3.07] death 6/379 6/379 Tau​2 = 0.29, I​2 = 45.8%, p = 0.35 Late treatment 29% 0.71 [0.35-1.44] 27/2,724 39/2,754 29% improvement Lilly (RCT) 57% 0.43 [0.28-0.67] symp. case 483 (n) 482 (n) Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.00021 Prophylaxis 57% 0.43 [0.28-0.67] 0/483 0/482 57% improvement All studies 55% 0.45 [0.29-0.70] 42/5,278 165/19,145 55% improvement 14 bamlanivimab/etesevimab COVID-19 studies c19ly.com Aug 2022 Tau​2 = 0.28, I​2 = 47.9%, p = 0.00041 Effect extraction pre-specified(most serious outcome, see appendix) Favors bamlanivimab/e.. Favors control
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Gottlieb (RCT) 71% hosp./ER Improvement Relative Risk [CI] Webb 80% death Dougan (DB RCT) 95% death Cooper 45% death Rubin 44% death Delasobera -119% death Dale 89% death Wilden 51% hospitalization Tau​2 = 0.31, I​2 = 37.9%, p = 0.00058 Early treatment 69% 69% improvement ACTIV-3/T.. (RCT) -100% death Bariola 67% death Ganesh 74% death Chew (RCT) 25% hospitalization Priest (PSM) 0% death Tau​2 = 0.29, I​2 = 45.8%, p = 0.35 Late treatment 29% 29% improvement Lilly (RCT) 57% symp. case Tau​2 = 0.00, I​2 = 0.0%, p = 0.00021 Prophylaxis 57% 57% improvement All studies 55% 55% improvement 14 bamlanivimab/etesevimab COVID-19 studies c19ly.com Aug 2022 Tau​2 = 0.28, I​2 = 47.9%, p = 0.00041 Effect extraction pre-specifiedRotate device for details Favors bamlanivimab/e.. 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 bamlanivimab/etesevimab 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 bamlanivimab/etesevimab is not effective for the omicron variant [Liu, Sheward, 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, and 12 show forest plots for a random effects meta-analysis of all studies with pooled effects, mortality results, ICU admission, hospitalization, progression, recovery, cases, viral clearance, and peer reviewed studies.
0 0.5 1 1.5+ ALL STUDIES MORTALITY ICU ADMISSION HOSPITALIZATION PROGRESSION RECOVERY CASES VIRAL CLEARANCE RANDOMIZED CONTROLLED TRIALS RCT MORTALITY PEER-REVIEWED After Exclusions ALL STUDIES All Prophylaxis Early Late Bamlanivimab/etesevimab for COVID-19 C19LY.COM AUG 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 7 8 87.5% 69% improvement
RR 0.31 [0.16‑0.60]
p = 0.00058
Late treatment 3 5 60.0% 29% improvement
RR 0.71 [0.35‑1.44]
p = 0.35
Prophylaxis 1 1 100% 57% improvement
RR 0.43 [0.28‑0.67]
p = 0.00021
All studies 11 14 78.6% 55% improvement
RR 0.45 [0.29‑0.70]
p = 0.00041
Table 1. Results by treatment stage.
Studies Early treatment Late treatment Prophylaxis PatientsAuthors
All studies 1469% [40‑84%]29% [-44‑65%]57% [33‑72%] 24,423 197
With exclusions 1272% [37‑88%]29% [-44‑65%]57% [33‑72%] 14,159 181
Peer-reviewed 1169% [40‑84%]10% [-164‑69%] 22,673 151
Randomized Controlled TrialsRCTs 579% [19‑95%]-21% [-218‑54%]57% [33‑72%] 2,784 85
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+ Gottlieb (RCT) 71% 0.29 [0.09-0.96] hosp./ER 4/101 7/52 Improvement, RR [CI] Treatment Control Webb 80% 0.20 [0.03-1.46] death 1/479 57/5,536 Dougan (DB RCT) 95% 0.05 [0.00-0.90] death 0/518 9/517 Cooper 45% 0.55 [0.07-3.99] death 1/473 33/8,534 Rubin 44% 0.56 [0.07-4.33] death 1/191 10/1,066 Delasobera -119% 2.19 [0.23-20.9] death 3/253 1/185 Dale 89% 0.11 [0.02-0.55] death 5/56 9/19 Wilden 51% 0.49 [0.23-1.04] hosp. n/a n/a Tau​2 = 0.31, I​2 = 37.9%, p = 0.00058 Early treatment 69% 0.31 [0.16-0.60] 15/2,071 126/15,909 69% improvement ACTIV-3/T.. (RCT) -100% 2.00 [0.69-5.83] death 9/163 5/151 Improvement, RR [CI] Treatment Control Bariola 67% 0.33 [0.10-1.01] death 4/234 12/234 Ganesh 74% 0.26 [0.05-1.20] death 2/1,789 8/1,832 Chew (RCT) 25% 0.75 [0.26-2.10] hosp. 6/159 8/158 Priest (PSM) 0% 1.00 [0.33-3.07] death 6/379 6/379 Tau​2 = 0.29, I​2 = 45.8%, p = 0.35 Late treatment 29% 0.71 [0.35-1.44] 27/2,724 39/2,754 29% improvement Lilly (RCT) 57% 0.43 [0.28-0.67] symp. case 483 (n) 482 (n) Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.00021 Prophylaxis 57% 0.43 [0.28-0.67] 0/483 0/482 57% improvement All studies 55% 0.45 [0.29-0.70] 42/5,278 165/19,145 55% improvement 14 bamlanivimab/etesevimab COVID-19 studies c19ly.com Aug 2022 Tau​2 = 0.28, I​2 = 47.9%, p = 0.00041 Effect extraction pre-specified(most serious outcome, see appendix) Favors bamlanivimab/e.. Favors control
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Gottlieb (RCT) 71% hosp./ER Improvement Relative Risk [CI] Webb 80% death Dougan (DB RCT) 95% death Cooper 45% death Rubin 44% death Delasobera -119% death Dale 89% death Wilden 51% hospitalization Tau​2 = 0.31, I​2 = 37.9%, p = 0.00058 Early treatment 69% 69% improvement ACTIV-3/T.. (RCT) -100% death Bariola 67% death Ganesh 74% death Chew (RCT) 25% hospitalization Priest (PSM) 0% death Tau​2 = 0.29, I​2 = 45.8%, p = 0.35 Late treatment 29% 29% improvement Lilly (RCT) 57% symp. case Tau​2 = 0.00, I​2 = 0.0%, p = 0.00021 Prophylaxis 57% 57% improvement All studies 55% 55% improvement 14 bamlanivimab/etesevimab COVID-19 studies c19ly.com Aug 2022 Tau​2 = 0.28, I​2 = 47.9%, p = 0.00041 Effect extraction pre-specifiedRotate device for details Favors bamlanivimab/e.. 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+ Webb 80% 0.20 [0.03-1.46] 1/479 57/5,536 Improvement, RR [CI] Treatment Control Dougan (DB RCT) 95% 0.05 [0.00-0.90] 0/518 9/517 Cooper 45% 0.55 [0.07-3.99] 1/473 33/8,534 Rubin 44% 0.56 [0.07-4.33] 1/191 10/1,066 Delasobera -119% 2.19 [0.23-20.9] 3/253 1/185 Dale 89% 0.11 [0.02-0.55] 5/56 9/19 Tau​2 = 0.64, I​2 = 42.3%, p = 0.012 Early treatment 72% 0.28 [0.10-0.76] 11/1,970 119/15,857 72% improvement ACTIV-3/T.. (RCT) -100% 2.00 [0.69-5.83] 9/163 5/151 Improvement, RR [CI] Treatment Control Bariola 67% 0.33 [0.10-1.01] 4/234 12/234 Ganesh 74% 0.26 [0.05-1.20] 2/1,789 8/1,832 Priest (PSM) 0% 1.00 [0.33-3.07] 6/379 6/379 Tau​2 = 0.54, I​2 = 59.3%, p = 0.45 Late treatment 31% 0.69 [0.27-1.76] 21/2,565 31/2,596 31% improvement All studies 56% 0.44 [0.20-0.95] 32/4,535 150/18,453 56% improvement 10 bamlanivimab/etesevimab COVID-19 mortality results c19ly.com Aug 2022 Tau​2 = 0.87, I​2 = 61.6%, p = 0.035 Favors bamlanivimab/e.. 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+ Cooper 58% 0.42 [0.10-1.72] 2/473 85/8,534 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.23 Early treatment 58% 0.42 [0.10-1.72] 2/473 85/8,534 58% improvement Ganesh 49% 0.51 [0.24-1.09] 10/1,789 20/1,832 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.082 Late treatment 49% 0.51 [0.24-1.09] 10/1,789 20/1,832 49% improvement All studies 51% 0.49 [0.25-0.95] 12/2,262 105/10,366 51% improvement 2 bamlanivimab/etesevimab COVID-19 ICU results c19ly.com Aug 2022 Tau​2 = 0.00, I​2 = 0.0%, p = 0.036 Favors bamlanivimab/e.. Favors control
Figure 6. Random effects meta-analysis for ICU admission.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Webb 53% 0.47 [0.31-0.72] hosp. 22/479 538/5,536 Improvement, RR [CI] Treatment Control Cooper 5% 0.95 [0.69-1.30] hosp. 37/473 703/8,534 Rubin 65% 0.35 [0.12-0.94] hosp. 16/191 121/1,065 Delasobera 52% 0.48 [0.27-0.85] hosp. 17/253 26/185 Wilden 51% 0.49 [0.23-1.04] hosp. n/a n/a Tau​2 = 0.16, I​2 = 73.0%, p = 0.0028 Early treatment 47% 0.53 [0.35-0.80] 92/1,396 1,388/15,320 47% improvement Bariola 61% 0.39 [0.22-0.70] hosp. 15/234 39/234 Improvement, RR [CI] Treatment Control Ganesh 37% 0.63 [0.43-0.91] hosp. 44/1,789 72/1,832 Chew (RCT) 25% 0.75 [0.26-2.10] hosp. 6/159 8/158 Priest (PSM) -4% 1.04 [0.78-1.38] hosp. 79/379 76/379 Tau​2 = 0.14, I​2 = 72.8%, p = 0.093 Late treatment 32% 0.68 [0.43-1.07] 144/2,561 195/2,603 32% improvement All studies 41% 0.59 [0.44-0.79] 236/3,957 1,583/17,923 41% improvement 9 bamlanivimab/etesevimab COVID-19 hospitalization results c19ly.com Aug 2022 Tau​2 = 0.13, I​2 = 72.4%, p = 0.00052 Favors bamlanivimab/e.. Favors control
Figure 7. Random effects meta-analysis for hospitalization.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Delasobera 20% 0.80 [0.46-1.40] 23/253 21/185 Improvement, RR [CI] Treatment Control Dale 86% 0.14 [0.04-0.52] 6/56 10/19 Tau​2 = 1.42, I​2 = 91.1%, p = 0.23 Early treatment 66% 0.34 [0.06-1.93] 29/309 31/204 66% improvement All studies 66% 0.34 [0.06-1.93] 29/309 31/204 66% improvement 2 bamlanivimab/etesevimab COVID-19 progression results c19ly.com Aug 2022 Tau​2 = 1.42, I​2 = 91.1%, p = 0.23 Favors bamlanivimab/e.. Favors control
Figure 8. Random effects meta-analysis for progression.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Dougan (DB RCT) 11% 0.89 [0.82-0.97] recov. time 518 (n) 517 (n) Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.0071 Early treatment 11% 0.89 [0.82-0.97] 0/518 0/517 11% improvement Chew (RCT) -14% 1.14 [0.00-455] recov. time 48 (n) 46 (n) Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.97 Late treatment -14% 1.14 [0.00-455] 0/48 0/46 -14% improvement All studies 11% 0.89 [0.82-0.97] 0/566 0/563 11% improvement 2 bamlanivimab/etesevimab COVID-19 recovery results c19ly.com Aug 2022 Tau​2 = 0.00, I​2 = 0.0%, p = 0.0071 Favors bamlanivimab/e.. Favors control
Figure 9. Random effects meta-analysis for recovery.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Lilly (RCT) 57% 0.43 [0.28-0.67] symp. case 483 (n) 482 (n) Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.00021 Prophylaxis 57% 0.43 [0.28-0.67] 0/483 0/482 57% improvement All studies 57% 0.43 [0.28-0.67] 0/483 0/482 57% improvement 1 bamlanivimab/etesevimab COVID-19 case result c19ly.com Aug 2022 Tau​2 = 0.00, I​2 = 0.0%, p = 0.00021 Favors bamlanivimab/e.. Favors control
Figure 10. Random effects meta-analysis for cases.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Dougan (DB RCT) 67% 0.33 [0.25-0.45] viral+ 50/508 147/499 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Early treatment 67% 0.33 [0.25-0.45] 50/508 147/499 67% improvement Chew (RCT) 26% 0.74 [0.62-0.90] viral load 48 (n) 46 (n) Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.002 Late treatment 26% 0.74 [0.62-0.90] 0/48 0/46 26% improvement All studies 50% 0.50 [0.23-1.10] 50/556 147/545 50% improvement 2 bamlanivimab/etesevimab COVID-19 viral clearance results c19ly.com Aug 2022 Tau​2 = 0.30, I​2 = 95.0%, p = 0.085 Favors bamlanivimab/e.. Favors control
Figure 11. Random effects meta-analysis for viral clearance.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Gottlieb (RCT) 71% 0.29 [0.09-0.96] hosp./ER 4/101 7/52 Improvement, RR [CI] Treatment Control Webb 80% 0.20 [0.03-1.46] death 1/479 57/5,536 Dougan (DB RCT) 95% 0.05 [0.00-0.90] death 0/518 9/517 Cooper 45% 0.55 [0.07-3.99] death 1/473 33/8,534 Rubin 44% 0.56 [0.07-4.33] death 1/191 10/1,066 Delasobera -119% 2.19 [0.23-20.9] death 3/253 1/185 Dale 89% 0.11 [0.02-0.55] death 5/56 9/19 Wilden 51% 0.49 [0.23-1.04] hosp. n/a n/a Tau​2 = 0.31, I​2 = 37.9%, p = 0.00058 Early treatment 69% 0.31 [0.16-0.60] 15/2,071 126/15,909 69% improvement ACTIV-3/T.. (RCT) -100% 2.00 [0.69-5.83] death 9/163 5/151 Improvement, RR [CI] Treatment Control Ganesh 74% 0.26 [0.05-1.20] death 2/1,789 8/1,832 Priest (PSM) 0% 1.00 [0.33-3.07] death 6/379 6/379 Tau​2 = 0.50, I​2 = 56.4%, p = 0.86 Late treatment 10% 0.90 [0.31-2.64] 17/2,331 19/2,362 10% improvement All studies 56% 0.44 [0.23-0.84] 32/4,402 145/18,271 56% improvement 11 bamlanivimab/etesevimab COVID-19 peer reviewed trials c19ly.com Aug 2022 Tau​2 = 0.62, I​2 = 57.8%, p = 0.013 Effect extraction pre-specified(most serious outcome, see appendix) Favors bamlanivimab/e.. Favors control
Figure 12. 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 13 shows a forest plot for random effects meta-analysis of all studies after exclusions.
[Cooper], unadjusted results with no group details.
[Rubin], significant unadjusted confounding possible.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Gottlieb (RCT) 71% 0.29 [0.09-0.96] hosp./ER 4/101 7/52 Improvement, RR [CI] Treatment Control Webb 80% 0.20 [0.03-1.46] death 1/479 57/5,536 Dougan (DB RCT) 95% 0.05 [0.00-0.90] death 0/518 9/517 Delasobera -119% 2.19 [0.23-20.9] death 3/253 1/185 Dale 89% 0.11 [0.02-0.55] death 5/56 9/19 Wilden 51% 0.49 [0.23-1.04] hosp. n/a n/a Tau​2 = 0.49, I​2 = 52.6%, p = 0.0021 Early treatment 72% 0.28 [0.12-0.63] 13/1,407 83/6,309 72% improvement ACTIV-3/T.. (RCT) -100% 2.00 [0.69-5.83] death 9/163 5/151 Improvement, RR [CI] Treatment Control Bariola 67% 0.33 [0.10-1.01] death 4/234 12/234 Ganesh 74% 0.26 [0.05-1.20] death 2/1,789 8/1,832 Chew (RCT) 25% 0.75 [0.26-2.10] hosp. 6/159 8/158 Priest (PSM) 0% 1.00 [0.33-3.07] death 6/379 6/379 Tau​2 = 0.29, I​2 = 45.8%, p = 0.35 Late treatment 29% 0.71 [0.35-1.44] 27/2,724 39/2,754 29% improvement Lilly (RCT) 57% 0.43 [0.28-0.67] symp. case 483 (n) 482 (n) Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.00021 Prophylaxis 57% 0.43 [0.28-0.67] 0/483 0/482 57% improvement All studies 56% 0.44 [0.27-0.72] 40/4,614 122/9,545 56% improvement 12 bamlanivimab/etesevimab COVID-19 studies after exclusions c19ly.com Aug 2022 Tau​2 = 0.34, I​2 = 55.7%, p = 0.00098 Effect extraction pre-specified(most serious outcome, see appendix) Favors bamlanivimab/e.. Favors control
Figure 13. 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 14 shows the distribution of results for Randomized Controlled Trials and other studies, and a chronological history of results. The median effect size for RCTs is 57% improvement, compared to 51% for other studies. Figure 15 and 16 show forest plots for a random effects meta-analysis of all Randomized Controlled Trials and RCT mortality results. Table 3 summarizes the results.
Figure 14. 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+ Gottlieb (RCT) 71% 0.29 [0.09-0.96] hosp./ER 4/101 7/52 Improvement, RR [CI] Treatment Control Dougan (DB RCT) 95% 0.05 [0.00-0.90] death 0/518 9/517 Tau​2 = 0.25, I​2 = 16.9%, p = 0.023 Early treatment 79% 0.21 [0.05-0.81] 4/619 16/569 79% improvement ACTIV-3/T.. (RCT) -100% 2.00 [0.69-5.83] death 9/163 5/151 Improvement, RR [CI] Treatment Control Chew (RCT) 25% 0.75 [0.26-2.10] hosp. 6/159 8/158 Tau​2 = 0.20, I​2 = 40.7%, p = 0.71 Late treatment -21% 1.21 [0.46-3.18] 15/322 13/309 -21% improvement Lilly (RCT) 57% 0.43 [0.28-0.67] symp. case 483 (n) 482 (n) Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.00021 Prophylaxis 57% 0.43 [0.28-0.67] 0/483 0/482 57% improvement All studies 45% 0.55 [0.26-1.18] 19/1,424 29/1,360 45% improvement 5 bamlanivimab/etesevimab COVID-19 Randomized Controlled Trials c19ly.com Aug 2022 Tau​2 = 0.42, I​2 = 62.4%, p = 0.12 Effect extraction pre-specified(most serious outcome, see appendix) Favors bamlanivimab/e.. Favors control
Figure 15. Random effects meta-analysis for all Randomized Controlled Trials. 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+ Dougan (DB RCT) 95% 0.05 [0.00-0.90] 0/518 9/517 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.042 Early treatment 95% 0.05 [0.00-0.90] 0/518 9/517 95% improvement ACTIV-3/T.. (RCT) -100% 2.00 [0.69-5.83] 9/163 5/151 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.21 Late treatment -100% 2.00 [0.69-5.83] 9/163 5/151 -100% improvement All studies 58% 0.42 [0.01-14.2] 9/681 14/668 58% improvement 2 bamlanivimab/etesevimab COVID-19 RCT mortality results c19ly.com Aug 2022 Tau​2 = 5.42, I​2 = 81.9%, p = 0.64