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Favipiravir for COVID-19: real-time meta analysis of 26 studies
Covid Analysis, January 16, 2022, DRAFT
https://c19favipiravir.com/meta.html
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ All studies 28% 26 6,386 Improvement, Studies, Patients Relative Risk With exclusions 28% 23 5,987 Mortality -3% 13 4,629 Ventilation 18% 5 1,659 ICU admission -21% 8 2,070 Hospitalization 2% 5 670 Progression 60% 4 585 Recovery 19% 16 3,466 Viral clearance 33% 12 2,064 RCTs 23% 16 3,032 Peer-reviewed 31% 21 4,742 Early 45% 6 1,472 Late 24% 20 4,914 Favipiravir for COVID-19 c19favipiravir.com Jan 16, 2022 Favors favipiravir Favors control
Statistically significant improvements are seen for progression, recovery, and viral clearance. 17 studies from 17 independent teams in 12 different countries show statistically significant improvements in isolation (9 for the most serious outcome).
Meta analysis using the most serious outcome reported shows 28% [11‑42%] 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.
Overall mortality results are negative, however this is dominated by late treatment studies. Early treatment shows positive results for mortality, but with very limited data.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ All studies 28% 26 6,386 Improvement, Studies, Patients Relative Risk With exclusions 28% 23 5,987 Mortality -3% 13 4,629 Ventilation 18% 5 1,659 ICU admission -21% 8 2,070 Hospitalization 2% 5 670 Progression 60% 4 585 Recovery 19% 16 3,466 Viral clearance 33% 12 2,064 RCTs 23% 16 3,032 Peer-reviewed 31% 21 4,742 Early 45% 6 1,472 Late 24% 20 4,914 Favipiravir for COVID-19 c19favipiravir.com Jan 16, 2022 Favors favipiravir Favors control
While many treatments have some level of efficacy, they do not replace vaccines and other measures to avoid infection. Only 4% of favipiravir studies show zero events in the treatment arm.
Multiple treatments are typically used in combination, and other treatments are more effective.
Elimination of COVID-19 is a race against viral evolution. No treatment, vaccine, or intervention is 100% available and effective for all variants. All practical, effective, and safe means should be used, including treatments, as supported by Pfizer [Pfizer]. 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.
Studies Early treatment Late treatment PatientsAuthors
All studies 2645% [11‑66%]24% [4‑40%] 6,386 466
With exclusions 2345% [11‑66%]24% [2‑41%] 5,987 444
Peer-reviewed 2145% [-26‑76%]28% [3‑46%] 4,742 375
Randomized Controlled TrialsRCTs 1630% [-79‑72%]21% [2‑36%] 3,032 333
Percentage improvement with favipiravir treatment
A
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Ruzhentsova (RCT) 6% 0.94 [0.78-1.14] hosp. 3/112 2/56 Improvement, RR [CI] Treatment Control Udwadia (RCT) 40% 0.60 [0.38-0.95] recov. time 75 (n) 75 (n) Sawanpanyalert 68% 0.32 [0.15-0.66] progression n/a n/a Holubar (DB RCT) 89% 0.11 [0.01-2.02] hosp. 0/75 4/74 Alattar (PSM) 33% 0.67 [0.28-1.61] death 8/387 12/387 Bosaeed (DB RCT) -619% 7.19 [0.38-138] ICU 3/112 0/119 Tau​2 = 0.09, I​2 = 26.0%, p = 0.015 Early treatment 45% 0.55 [0.34-0.89] 14/761 18/711 45% improvement Cai 69% 0.31 [0.10-0.96] pneumonia 35 (n) 45 (n) Improvement, RR [CI] Treatment Control Ivashchenko (RCT) 46% 0.54 [0.33-0.88] viral+ 15/40 14/20 Pushkar (RCT) 14% 0.86 [0.74-0.99] no recov. 73/100 85/100 Khamis (RCT) 15% 0.85 [0.28-2.59] death 5/44 6/45 OT​1 CT​2 Solaymani-.. (RCT) -19% 1.19 [0.70-2.04] death 26/190 21/183 OT​1 Zhao (RCT) 59% 0.41 [0.18-0.93] viral+ 7/36 9/19 Aghajani 26% 0.74 [0.43-1.27] death 40 (n) 951 (n) Alamer -56% 1.56 [0.73-3.36] death 12/233 21/223 Almoosa -42% 1.42 [0.90-2.25] death 33/110 24/116 Shinkai (SB RCT) 37% 0.63 [0.40-0.98] imp. time 107 (n) 49 (n) Assiri -79% 1.79 [0.33-8.02] death 11/67 3/51 Kulzhanova 88% 0.12 [0.04-0.37] no improv. 3/40 25/40 Chen (RCT) -3% 1.03 [0.15-7.22] ICU 2/116 2/120 OT​1 Alotaibi 57% 0.43 [0.18-1.01] death 244 (n) 193 (n) OT​1 Tabarsi (RCT) 30% 0.70 [0.17-2.88] death 3/32 4/30 OT​1 Atipornwan.. (RCT) 23% 0.77 [0.35-1.67] death 10/100 13/100 CT​2 Damayanti 54% 0.46 [0.22-0.92] no recov. 96 (n) 96 (n) Shenoy (DB RCT) -29% 1.29 [0.60-2.77] death 14/175 11/178 Chuah (RCT) -1154% 12.54 [0.76-208] death 5/250 0/250 Finberg (RCT) -200% 3.00 [0.13-70.3] death 1/25 0/25 Tau​2 = 0.12, I​2 = 58.0%, p = 0.024 Late treatment 24% 0.76 [0.60-0.96] 220/2,080 238/2,834 24% improvement All studies 28% 0.72 [0.58-0.89] 234/2,841 256/3,545 28% improvement 26 favipiravir COVID-19 studies c19favipiravir.com Jan 16, 2022 Tau​2 = 0.12, I​2 = 55.9%, p = 0.0029 Effect extraction pre-specified, see appendix 1 OT: comparison with other treatment2 CT: study uses combined treatment Favors favipiravir 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 favipiravir 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.
Results
Figure 3, 4, 5, 6, 7, 8, 9, 10, and 11 show forest plots for a random effects meta-analysis of all studies with pooled effects, mortality results, ventilation, ICU admission, hospitalization, progression, recovery, viral clearance, and peer reviewed studies. Table 1 summarizes the results by treatment stage.
Treatment timeNumber of studies reporting positive effects Total number of studiesPercentage of studies reporting positive effects Random effects meta-analysis results
Early treatment 5 6 83.3% 45% improvement
RR 0.55 [0.34‑0.89]
p = 0.015
Late treatment 12 20 60.0% 24% improvement
RR 0.76 [0.60‑0.96]
p = 0.024
All studies 17 26 65.4% 28% improvement
RR 0.72 [0.58‑0.89]
p = 0.0029
Table 1. Results by treatment stage.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Ruzhentsova (RCT) 6% 0.94 [0.78-1.14] hosp. 3/112 2/56 Improvement, RR [CI] Treatment Control Udwadia (RCT) 40% 0.60 [0.38-0.95] recov. time 75 (n) 75 (n) Sawanpanyalert 68% 0.32 [0.15-0.66] progression n/a n/a Holubar (DB RCT) 89% 0.11 [0.01-2.02] hosp. 0/75 4/74 Alattar (PSM) 33% 0.67 [0.28-1.61] death 8/387 12/387 Bosaeed (DB RCT) -619% 7.19 [0.38-138] ICU 3/112 0/119 Tau​2 = 0.09, I​2 = 26.0%, p = 0.015 Early treatment 45% 0.55 [0.34-0.89] 14/761 18/711 45% improvement Cai 69% 0.31 [0.10-0.96] pneumonia 35 (n) 45 (n) Improvement, RR [CI] Treatment Control Ivashchenko (RCT) 46% 0.54 [0.33-0.88] viral+ 15/40 14/20 Pushkar (RCT) 14% 0.86 [0.74-0.99] no recov. 73/100 85/100 Khamis (RCT) 15% 0.85 [0.28-2.59] death 5/44 6/45 OT​1 CT​2 Solaymani-.. (RCT) -19% 1.19 [0.70-2.04] death 26/190 21/183 OT​1 Zhao (RCT) 59% 0.41 [0.18-0.93] viral+ 7/36 9/19 Aghajani 26% 0.74 [0.43-1.27] death 40 (n) 951 (n) Alamer -56% 1.56 [0.73-3.36] death 12/233 21/223 Almoosa -42% 1.42 [0.90-2.25] death 33/110 24/116 Shinkai (SB RCT) 37% 0.63 [0.40-0.98] imp. time 107 (n) 49 (n) Assiri -79% 1.79 [0.33-8.02] death 11/67 3/51 Kulzhanova 88% 0.12 [0.04-0.37] no improv. 3/40 25/40 Chen (RCT) -3% 1.03 [0.15-7.22] ICU 2/116 2/120 OT​1 Alotaibi 57% 0.43 [0.18-1.01] death 244 (n) 193 (n) OT​1 Tabarsi (RCT) 30% 0.70 [0.17-2.88] death 3/32 4/30 OT​1 Atipornwan.. (RCT) 23% 0.77 [0.35-1.67] death 10/100 13/100 CT​2 Damayanti 54% 0.46 [0.22-0.92] no recov. 96 (n) 96 (n) Shenoy (DB RCT) -29% 1.29 [0.60-2.77] death 14/175 11/178 Chuah (RCT) -1154% 12.54 [0.76-208] death 5/250 0/250 Finberg (RCT) -200% 3.00 [0.13-70.3] death 1/25 0/25 Tau​2 = 0.12, I​2 = 58.0%, p = 0.024 Late treatment 24% 0.76 [0.60-0.96] 220/2,080 238/2,834 24% improvement All studies 28% 0.72 [0.58-0.89] 234/2,841 256/3,545 28% improvement 26 favipiravir COVID-19 studies c19favipiravir.com Jan 16, 2022 Tau​2 = 0.12, I​2 = 55.9%, p = 0.0029 Effect extraction pre-specified, see appendix 1 OT: comparison with other treatment2 CT: study uses combined treatment Favors favipiravir Favors control
Figure 3. 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+ Alattar (PSM) 33% 0.67 [0.28-1.61] 8/387 12/387 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.37 Early treatment 33% 0.67 [0.28-1.61] 8/387 12/387 33% improvement Khamis (RCT) 15% 0.85 [0.28-2.59] 5/44 6/45 OT​1 CT​2 Improvement, RR [CI] Treatment Control Solaymani-.. (RCT) -19% 1.19 [0.70-2.04] 26/190 21/183 OT​1 Aghajani 26% 0.74 [0.43-1.27] 40 (n) 951 (n) Alamer -56% 1.56 [0.73-3.36] 12/233 21/223 Almoosa -42% 1.42 [0.90-2.25] 33/110 24/116 Assiri -79% 1.79 [0.33-8.02] 11/67 3/51 Alotaibi 57% 0.43 [0.18-1.01] 244 (n) 193 (n) OT​1 Tabarsi (RCT) 30% 0.70 [0.17-2.88] 3/32 4/30 OT​1 Atipornwan.. (RCT) 23% 0.77 [0.35-1.67] 10/100 13/100 CT​2 Shenoy (DB RCT) -29% 1.29 [0.60-2.77] 14/175 11/178 Chuah (RCT) -1154% 12.54 [0.76-208] 5/250 0/250 Finberg (RCT) -200% 3.00 [0.13-70.3] 1/25 0/25 Tau​2 = 0.05, I​2 = 23.3%, p = 0.66 Late treatment -6% 1.06 [0.81-1.39] 120/1,510 103/2,345 -6% improvement All studies -3% 1.03 [0.80-1.33] 128/1,897 115/2,732 -3% improvement 13 favipiravir COVID-19 mortality results c19favipiravir.com Jan 16, 2022 Tau​2 = 0.05, I​2 = 22.2%, p = 0.83 1 OT: comparison with other treatment2 CT: study uses combined treatment Favors favipiravir Favors control
Figure 4. Random effects meta-analysis for mortality results.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Solaymani-.. (RCT) -53% 1.53 [0.86-2.71] 27/190 17/183 OT​1 Improvement, RR [CI] Treatment Control Alamer 90% 0.10 [0.04-0.29] 4/218 27/165 Shenoy (DB RCT) -33% 1.33 [0.67-2.66] 17/175 13/178 Chuah (RCT) -20% 1.20 [0.36-3.97] 6/250 5/250 Finberg (RCT) -200% 3.00 [0.13-70.3] 1/25 0/25 Tau​2 = 1.02, I​2 = 82.2%, p = 0.72 Late treatment 18% 0.82 [0.29-2.32] 55/858 62/801 18% improvement All studies 18% 0.82 [0.29-2.32] 55/858 62/801 18% improvement 5 favipiravir COVID-19 mechanical ventilation results c19favipiravir.com Jan 16, 2022 Tau​2 = 1.02, I​2 = 82.2%, p = 0.72 1 OT: comparison with other treatment Favors favipiravir Favors control
Figure 5. Random effects meta-analysis for ventilation.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Bosaeed (DB RCT) -619% 7.19 [0.38-138] 3/112 0/119 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.19 Early treatment -619% 7.19 [0.38-138] 3/112 0/119 -619% improvement Khamis (RCT) -2% 1.02 [0.42-2.48] 8/44 8/45 OT​1 CT​2 Improvement, RR [CI] Treatment Control Solaymani-.. (RCT) -19% 1.19 [0.73-1.94] 31/190 25/183 OT​1 Almoosa -90% 1.90 [1.11-3.26] 110 (n) 116 (n) Chen (RCT) -3% 1.03 [0.15-7.22] 2/116 2/120 OT​1 Tabarsi (RCT) 41% 0.59 [0.22-1.59] 5/32 8/30 OT​1 Shenoy (DB RCT) -2% 1.02 [0.57-1.82] 20/175 20/178 Chuah (RCT) -9% 1.09 [0.49-2.31] 13/250 12/250 Tau​2 = 0.00, I​2 = 0.0%, p = 0.18 Late treatment -19% 1.19 [0.92-1.55] 79/917 75/922 -19% improvement All studies -21% 1.21 [0.93-1.57] 82/1,029 75/1,041 -21% improvement 8 favipiravir COVID-19 ICU results c19favipiravir.com Jan 16, 2022 Tau​2 = 0.00, I​2 = 0.0%, p = 0.15 1 OT: comparison with other treatment2 CT: study uses combined treatment Favors favipiravir 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+ Ruzhentsova (RCT) 6% 0.94 [0.78-1.14] hosp. 3/112 2/56 Improvement, RR [CI] Treatment Control Holubar (DB RCT) 89% 0.11 [0.01-2.02] hosp. 0/75 4/74 Bosaeed (DB RCT) -219% 3.19 [0.66-15.5] hosp. 6/112 2/119 Tau​2 = 1.09, I​2 = 51.6%, p = 0.98 Early treatment 3% 0.97 [0.19-5.08] 9/299 8/249 3% improvement Ivashchenko (RCT) -300% 4.00 [0.20-79.6] hosp. 2/40 0/20 Improvement, RR [CI] Treatment Control Tabarsi (RCT) 25% 0.75 [0.58-0.97] hosp. time 32 (n) 30 (n) OT​1 Tau​2 = 0.23, I​2 = 16.3%, p = 0.78 Late treatment 13% 0.87 [0.34-2.20] 2/72 0/50 13% improvement All studies 2% 0.98 [0.44-2.19] 11/371 8/299 2% improvement 5 favipiravir COVID-19 hospitalization results c19favipiravir.com Jan 16, 2022 Tau​2 = 0.29, I​2 = 34.1%, p = 0.97 1 OT: comparison with other treatment Favors favipiravir 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+ Sawanpanyalert 68% 0.32 [0.15-0.66] n/a n/a Improvement, RR [CI] Treatment Control Holubar (DB RCT) 30% 0.70 [0.23-2.12] 5/75 7/74 Tau​2 = 0.08, I​2 = 25.8%, p = 0.025 Early treatment 57% 0.43 [0.20-0.90] 5/75 7/74 57% improvement Chen (RCT) 74% 0.26 [0.03-2.28] 1/116 4/120 OT​1 Improvement, RR [CI] Treatment Control Atipornwan.. (RCT) 60% 0.40 [0.20-0.79] 10/100 25/100 CT​2 Tau​2 = 0.00, I​2 = 0.0%, p = 0.0039 Late treatment 62% 0.38 [0.20-0.74] 11/216 29/220 62% improvement All studies 60% 0.40 [0.25-0.62] 16/291 36/294 60% improvement 4 favipiravir COVID-19 progression results c19favipiravir.com Jan 16, 2022 Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 1 OT: comparison with other treatment2 CT: study uses combined treatment Favors favipiravir 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+ Ruzhentsova (RCT) 39% 0.61 [0.43-0.88] no recov. 112 (n) 56 (n) Improvement, RR [CI] Treatment Control Udwadia (RCT) 40% 0.60 [0.38-0.95] recov. time 75 (n) 75 (n) Holubar (DB RCT) 16% 0.84 [0.54-1.29] no recov. 65 (n) 70 (n) Alattar (PSM) -2% 1.02 [0.90-1.16] no recov. 26/387 28/387 Bosaeed (DB RCT) -12% 1.12 [0.80-1.56] no recov. 112 (n) 119 (n) Tau​2 = 0.05, I​2 = 53.1%, p = 0.13 Early treatment 19% 0.81 [0.62-1.06] 26/751 28/707 19% improvement Ivashchenko (RCT) -67% 1.67 [0.52-5.39] no disch. 10/40 3/20 Improvement, RR [CI] Treatment Control Pushkar (RCT) 14% 0.86 [0.74-0.99] no recov. 73/100 85/100 Khamis (RCT) -10% 1.10 [0.60-1.99] no recov. 15/44 14/45 OT​1 CT​2 Alamer 49% 0.51 [0.41-0.64] no disch. 221 (n) 201 (n) Almoosa -11% 1.11 [0.96-1.29] recov. time 110 (n) 116 (n) Shinkai (SB RCT) 37% 0.63 [0.40-0.98] imp. time 107 (n) 49 (n) Chen (RCT) 20% 0.80 [0.60-1.08] no recov. 45/116 58/120 OT​1 Tabarsi (RCT) 6% 0.94 [0.72-1.23] CT imp. 24/32 24/30 OT​1 Damayanti 54% 0.46 [0.22-0.92] no recov. 96 (n) 96 (n) Shenoy (DB RCT) -1% 1.01 [0.78-1.30] no recov. 157 (n) 158 (n) Finberg (RCT) 58% 0.42 [0.16-1.10] no recov. 25 (n) 25 (n) Tau​2 = 0.06, I​2 = 77.1%, p = 0.029 Late treatment 19% 0.81 [0.67-0.98] 167/1,048 184/960 19% improvement All studies 19% 0.81 [0.70-0.95] 193/1,799 212/1,667 19% improvement 16 favipiravir COVID-19 recovery results c19favipiravir.com Jan 16, 2022 Tau​2 = 0.06, I​2 = 71.4%, p = 0.0073 1 OT: comparison with other treatment2 CT: study uses combined treatment Favors favipiravir 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+ Ruzhentsova (RCT) 22% 0.78 [0.92-1.79] viral+ 112 (n) 56 (n) Improvement, RR [CI] Treatment Control Udwadia (RCT) 29% 0.71 [0.46-1.10] viral time 75 (n) 75 (n) Holubar (DB RCT) -32% 1.32 [0.83-2.08] viral+ 59 (n) 57 (n) Alattar (PSM) 44% 0.56 [0.44-0.71] viral+ 78/387 139/387 Bosaeed (DB RCT) -15% 1.15 [0.75-1.75] viral+ 112 (n) 119 (n) Tau​2 = 0.10, I​2 = 74.8%, p = 0.29 Early treatment 16% 0.84 [0.61-1.16] 78/745 139/694 16% improvement Cai 71% 0.29 [0.10-0.86] viral+ 35 (n) 45 (n) Improvement, RR [CI] Treatment Control Ivashchenko (RCT) 46% 0.54 [0.33-0.88] viral+ 15/40 14/20 Pushkar (RCT) 90% 0.10 [0.02-0.40] viral+ 2/100 21/100 Zhao (RCT) 59% 0.41 [0.18-0.93] viral+ 7/36 9/19 Kulzhanova 50% 0.50 [0.21-1.20] viral+ 6/40 12/40 Atipornwan.. (RCT) 9% 0.91 [0.73-1.14] viral time 50 (n) 50 (n) CT​1 Finberg (RCT) 47% 0.53 [0.29-0.98] viral time 25 (n) 25 (n) Tau​2 = 0.21, I​2 = 69.5%, p = 0.0013 Late treatment 52% 0.48 [0.31-0.75] 30/326 56/299 52% improvement All studies 33% 0.67 [0.53-0.86] 108/1,071 195/993 33% improvement 12 favipiravir COVID-19 viral clearance results c19favipiravir.com Jan 16, 2022 Tau​2 = 0.11, I​2 = 69.3%, p = 0.0014 1 CT: study uses combined treatment Favors favipiravir Favors control
Figure 10. Random effects meta-analysis for viral clearance.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Udwadia (RCT) 40% 0.60 [0.38-0.95] recov. time 75 (n) 75 (n) Improvement, RR [CI] Treatment Control Sawanpanyalert 68% 0.32 [0.15-0.66] progression n/a n/a Bosaeed (DB RCT) -619% 7.19 [0.38-138] ICU 3/112 0/119 Tau​2 = 0.28, I​2 = 60.1%, p = 0.16 Early treatment 45% 0.55 [0.24-1.26] 3/187 0/194 45% improvement Cai 69% 0.31 [0.10-0.96] pneumonia 35 (n) 45 (n) Improvement, RR [CI] Treatment Control Ivashchenko (RCT) 46% 0.54 [0.33-0.88] viral+ 15/40 14/20 Khamis (RCT) 15% 0.85 [0.28-2.59] death 5/44 6/45 OT​1 CT​2 Solaymani-.. (RCT) -19% 1.19 [0.70-2.04] death 26/190 21/183 OT​1 Zhao (RCT) 59% 0.41 [0.18-0.93] viral+ 7/36 9/19 Aghajani 26% 0.74 [0.43-1.27] death 40 (n) 951 (n) Alamer -56% 1.56 [0.73-3.36] death 12/233 21/223 Almoosa -42% 1.42 [0.90-2.25] death 33/110 24/116 Shinkai (SB RCT) 37% 0.63 [0.40-0.98] imp. time 107 (n) 49 (n) Assiri -79% 1.79 [0.33-8.02] death 11/67 3/51 Kulzhanova 88% 0.12 [0.04-0.37] no improv. 3/40 25/40 Chen (RCT) -3% 1.03 [0.15-7.22] ICU 2/116 2/120 OT​1 Alotaibi 57% 0.43 [0.18-1.01] death 244 (n) 193 (n) OT​1 Tabarsi (RCT) 30% 0.70 [0.17-2.88] death 3/32 4/30 OT​1 Atipornwan.. (RCT) 23% 0.77 [0.35-1.67] death 10/100 13/100 CT​2 Damayanti 54% 0.46 [0.22-0.92] no recov. 96 (n) 96 (n) Chuah (RCT) -1154% 12.54 [0.76-208] death 5/250 0/250 Finberg (RCT) -200% 3.00 [0.13-70.3] death 1/25 0/25 Tau​2 = 0.21, I​2 = 59.9%, p = 0.032 Late treatment 28% 0.72 [0.54-0.97] 133/1,805 142/2,556 28% improvement All studies 31% 0.69 [0.53-0.91] 136/1,992 142/2,750 31% improvement 21 favipiravir COVID-19 peer reviewed trials c19favipiravir.com Jan 16, 2022 Tau​2 = 0.20, I​2 = 60.0%, p = 0.0088 Effect extraction pre-specified, see appendix 1 OT: comparison with other treatment2 CT: study uses combined treatment Favors favipiravir Favors control
Figure 11. Random effects meta-analysis for peer reviewed studies. 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 12 shows a forest plot for random effects meta-analysis of all studies after exclusions.
[Assiri], unadjusted results with no group details.
[Damayanti], minimal details provided.
[Khamis], trials compares against another treatment showing significant efficacy in trials.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Ruzhentsova (RCT) 6% 0.94 [0.78-1.14] hosp. 3/112 2/56 Improvement, RR [CI] Treatment Control Udwadia (RCT) 40% 0.60 [0.38-0.95] recov. time 75 (n) 75 (n) Sawanpanyalert 68% 0.32 [0.15-0.66] progression n/a n/a Holubar (DB RCT) 89% 0.11 [0.01-2.02] hosp. 0/75 4/74 Alattar (PSM) 33% 0.67 [0.28-1.61] death 8/387 12/387 Bosaeed (DB RCT) -619% 7.19 [0.38-138] ICU 3/112 0/119 Tau​2 = 0.09, I​2 = 26.0%, p = 0.015 Early treatment