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Famotidine for COVID-19: real-time meta analysis of 23 studies
Covid Analysis, August 14, 2022, DRAFT
https://c19early.com/fmmeta.html
0 0.5 1 1.5+ All studies 15% 23 76,267 Improvement, Studies, Patients Relative Risk Mortality 17% 16 70,199 Ventilation 12% 1 178 ICU admission -70% 3 846 Hospitalization 14% 4 377 Recovery 11% 5 739 Cases 0% 3 307 RCTs 33% 3 253 Peer-reviewed 14% 22 76,247 Prophylaxis 13% 9 28,827 Early 48% 1 55 Late 11% 13 47,385 Famotidine for COVID-19 c19early.com/fm Aug 2022 Favorsfamotidine Favorscontrol after exclusions
Statistically significant improvements are seen for mortality, hospitalization, and recovery. 12 studies from 12 independent teams in 5 different countries show statistically significant improvements in isolation (8 for the most serious outcome).
Meta analysis using the most serious outcome reported shows 15% [4‑25%] improvement. Results are better for Randomized Controlled Trials, similar after exclusions, and similar for peer-reviewed studies. Early treatment is more effective than late treatment.
In exclusion sensitivity analysis, statistical significance is lost after excluding only one of 23 studies in pooled analysis.
0 0.5 1 1.5+ All studies 15% 23 76,267 Improvement, Studies, Patients Relative Risk Mortality 17% 16 70,199 Ventilation 12% 1 178 ICU admission -70% 3 846 Hospitalization 14% 4 377 Recovery 11% 5 739 Cases 0% 3 307 RCTs 33% 3 253 Peer-reviewed 14% 22 76,247 Prophylaxis 13% 9 28,827 Early 48% 1 55 Late 11% 13 47,385 Famotidine for COVID-19 c19early.com/fm Aug 2022 Favorsfamotidine Favorscontrol after exclusions
While many treatments have some level of efficacy, they do not replace vaccines and other measures to avoid infection. None of the famotidine studies show zero events in the treatment arm. Multiple treatments are typically used in combination, and other treatments are significantly 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
Famotidine reduces risk for COVID-19 with very high confidence for hospitalization, recovery, and in pooled analysis, and high confidence for mortality.
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+ Brennan (DB RCT) 48% 0.52 [0.20-1.32] no recov. 5/27 10/28 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.17 Early treatment 48% 0.52 [0.20-1.32] 5/27 10/28 48% improvement Shoaibi -3% 1.03 [0.89-1.18] death 1,816 (n) 26,820 (n) Improvement, RR [CI] Treatment Control Zhou (PSM) -81% 1.81 [1.28-2.58] severe case 72/519 198/2,595 Yeramaneni -59% 1.59 [0.94-2.71] death 410 (n) 746 (n) Mura (PSM) 21% 0.79 [0.65-0.96] death 563 (n) 563 (n) Samim.. (SB RCT) 33% 0.67 [0.45-0.98] hosp. time 10 (n) 10 (n) Elhadi (ICU) 7% 0.93 [0.73-1.17] death 34/60 247/405 ICU patients Taşdemir 45% 0.55 [0.20-1.55] death 5/85 10/94 OT​1 Kuno (PSM) 0% 1.00 [0.86-1.17] death 1,593 (n) 7,972 (n) Stolow -519% 6.19 [2.10-18.3] death 137 (n) 352 (n) Wagner 70% 0.30 [0.20-0.44] death 638 (n) 819 (n) Pahwani (RCT) 11% 0.89 [0.36-2.20] death 8/89 9/89 Siraj 36% 0.64 [0.48-0.83] death 183/711 122/289 Zangeneh (ICU) 39% 0.61 [0.42-0.90] death n/a n/a ICU patients Tau​2 = 0.13, I​2 = 88.4%, p = 0.31 Late treatment 11% 0.89 [0.70-1.12] 302/6,631 586/40,754 11% improvement Freedberg (PSM) 57% 0.43 [0.21-0.86] death/int. 8/84 332/1,536 Improvement, RR [CI] Treatment Control Mather (PSM) 61% 0.39 [0.20-0.74] death 83 (n) 689 (n) Balouch 22% 0.78 [0.36-1.51] symp. case 18/80 49/227 Yeramaneni 51% 0.49 [0.16-1.52] death 351 (n) 6,807 (n) Cheung -34% 1.34 [0.24-6.06] severe case 23 (n) 929 (n) Fung 0% 1.00 [0.96-1.04] death population-based cohort Razjouyan 27% 0.73 [0.59-0.92] death 93 (n) 9,981 (n) Wallace -11% 1.11 [0.89-1.35] death 98/423 1,436/7,521 MacFadden 7% 0.93 [0.84-1.03] cases n/a n/a Tau​2 = 0.02, I​2 = 70.2%, p = 0.048 Prophylaxis 13% 0.87 [0.76-1.00] 124/1,137 1,817/27,690 13% improvement All studies 15% 0.85 [0.75-0.96] 431/7,795 2,413/68,472 15% improvement 23 famotidine COVID-19 studies c19early.com/fm Aug 2022 Tau​2 = 0.05, I​2 = 83.8%, p = 0.0088 Effect extraction pre-specified(most serious outcome, see appendix) 1 OT: comparison with other treatment Favors famotidine Favors control
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Brennan (DB RCT) 48% recovery Improvement Relative Risk [CI] Tau​2 = 0.00, I​2 = 0.0%, p = 0.17 Early treatment 48% 48% improvement Shoaibi -3% death Zhou (PSM) -81% severe case Yeramaneni -59% death Mura (PSM) 21% death Samim.. (SB RCT) 33% hospitalization Elhadi (ICU) 7% death ICU patients Taşdemir 45% death OT​1 Kuno (PSM) 0% death Stolow -519% death Wagner 70% death Pahwani (RCT) 11% death Siraj 36% death Zangeneh (ICU) 39% death ICU patients Tau​2 = 0.13, I​2 = 88.4%, p = 0.31 Late treatment 11% 11% improvement Freedberg (PSM) 57% death/intubation Mather (PSM) 61% death Balouch 22% symp. case Yeramaneni 51% death Cheung -34% severe case Fung 0% death Razjouyan 27% death Wallace -11% death MacFadden 7% case Tau​2 = 0.02, I​2 = 70.2%, p = 0.048 Prophylaxis 13% 13% improvement All studies 15% 15% improvement 23 famotidine COVID-19 studies c19early.com/fm Aug 2022 Tau​2 = 0.05, I​2 = 83.8%, p = 0.0088 Protocol pre-specified/rotate for details1 OT: comparison with other treatment Favors famotidine 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 famotidine 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.
Preclinical Research
An In Vitro study supports the efficacy of famotidine [Loffredo].
Preclinical research is an important part of the development of treatments, however results may be very different in clinical trials. Preclinical results are not used in this paper.
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, and 11 show forest plots for a random effects meta-analysis of all studies with pooled effects, mortality results, ventilation, ICU admission, hospitalization, recovery, cases, and peer reviewed studies.
0 0.5 1 1.5+ ALL STUDIES MORTALITY VENTILATION ICU ADMISSION HOSPITALIZATION RECOVERY CASES RANDOMIZED CONTROLLED TRIALS PEER-REVIEWED After Exclusions ALL STUDIES All Prophylaxis Early Late Famotidine for COVID-19 C19EARLY.COM/FM 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 1 1 100% 48% improvement
RR 0.52 [0.20‑1.32]
p = 0.17
Late treatment 8 13 61.5% 11% improvement
RR 0.89 [0.70‑1.12]
p = 0.31
Prophylaxis 6 9 66.7% 13% improvement
RR 0.87 [0.76‑1.00]
p = 0.048
All studies 15 23 65.2% 15% improvement
RR 0.85 [0.75‑0.96]
p = 0.0088
Table 1. Results by treatment stage.
Studies Early treatment Late treatment Prophylaxis PatientsAuthors
All studies 2348% [-32‑80%]11% [-12‑30%]13% [0‑24%] 76,267 191
With exclusions 2048% [-32‑80%]10% [-17‑30%]21% [3‑36%] 75,623 157
Peer-reviewed 2248% [-32‑80%]9% [-16‑29%]13% [0‑24%] 76,247 185
Randomized Controlled TrialsRCTs 348% [-32‑80%]30% [0‑51%] 253 45
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+ Brennan (DB RCT) 48% 0.52 [0.20-1.32] no recov. 5/27 10/28 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.17 Early treatment 48% 0.52 [0.20-1.32] 5/27 10/28 48% improvement Shoaibi -3% 1.03 [0.89-1.18] death 1,816 (n) 26,820 (n) Improvement, RR [CI] Treatment Control Zhou (PSM) -81% 1.81 [1.28-2.58] severe case 72/519 198/2,595 Yeramaneni -59% 1.59 [0.94-2.71] death 410 (n) 746 (n) Mura (PSM) 21% 0.79 [0.65-0.96] death 563 (n) 563 (n) Samim.. (SB RCT) 33% 0.67 [0.45-0.98] hosp. time 10 (n) 10 (n) Elhadi (ICU) 7% 0.93 [0.73-1.17] death 34/60 247/405 ICU patients Taşdemir 45% 0.55 [0.20-1.55] death 5/85 10/94 OT​1 Kuno (PSM) 0% 1.00 [0.86-1.17] death 1,593 (n) 7,972 (n) Stolow -519% 6.19 [2.10-18.3] death 137 (n) 352 (n) Wagner 70% 0.30 [0.20-0.44] death 638 (n) 819 (n) Pahwani (RCT) 11% 0.89 [0.36-2.20] death 8/89 9/89 Siraj 36% 0.64 [0.48-0.83] death 183/711 122/289 Zangeneh (ICU) 39% 0.61 [0.42-0.90] death n/a n/a ICU patients Tau​2 = 0.13, I​2 = 88.4%, p = 0.31 Late treatment 11% 0.89 [0.70-1.12] 302/6,631 586/40,754 11% improvement Freedberg (PSM) 57% 0.43 [0.21-0.86] death/int. 8/84 332/1,536 Improvement, RR [CI] Treatment Control Mather (PSM) 61% 0.39 [0.20-0.74] death 83 (n) 689 (n) Balouch 22% 0.78 [0.36-1.51] symp. case 18/80 49/227 Yeramaneni 51% 0.49 [0.16-1.52] death 351 (n) 6,807 (n) Cheung -34% 1.34 [0.24-6.06] severe case 23 (n) 929 (n) Fung 0% 1.00 [0.96-1.04] death population-based cohort Razjouyan 27% 0.73 [0.59-0.92] death 93 (n) 9,981 (n) Wallace -11% 1.11 [0.89-1.35] death 98/423 1,436/7,521 MacFadden 7% 0.93 [0.84-1.03] cases n/a n/a Tau​2 = 0.02, I​2 = 70.2%, p = 0.048 Prophylaxis 13% 0.87 [0.76-1.00] 124/1,137 1,817/27,690 13% improvement All studies 15% 0.85 [0.75-0.96] 431/7,795 2,413/68,472 15% improvement 23 famotidine COVID-19 studies c19early.com/fm Aug 2022 Tau​2 = 0.05, I​2 = 83.8%, p = 0.0088 Effect extraction pre-specified(most serious outcome, see appendix) 1 OT: comparison with other treatment Favors famotidine Favors control
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Brennan (DB RCT) 48% recovery Improvement Relative Risk [CI] Tau​2 = 0.00, I​2 = 0.0%, p = 0.17 Early treatment 48% 48% improvement Shoaibi -3% death Zhou (PSM) -81% severe case Yeramaneni -59% death Mura (PSM) 21% death Samim.. (SB RCT) 33% hospitalization Elhadi (ICU) 7% death ICU patients Taşdemir 45% death OT​1 Kuno (PSM) 0% death Stolow -519% death Wagner 70% death Pahwani (RCT) 11% death Siraj 36% death Zangeneh (ICU) 39% death ICU patients Tau​2 = 0.13, I​2 = 88.4%, p = 0.31 Late treatment 11% 11% improvement Freedberg (PSM) 57% death/intubation Mather (PSM) 61% death Balouch 22% symp. case Yeramaneni 51% death Cheung -34% severe case Fung 0% death Razjouyan 27% death Wallace -11% death MacFadden 7% case Tau​2 = 0.02, I​2 = 70.2%, p = 0.048 Prophylaxis 13% 13% improvement All studies 15% 15% improvement 23 famotidine COVID-19 studies c19early.com/fm Aug 2022 Tau​2 = 0.05, I​2 = 83.8%, p = 0.0088 Protocol pre-specified/rotate for details1 OT: comparison with other treatment Favors famotidine 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+ Shoaibi -3% 1.03 [0.89-1.18] 1,816 (n) 26,820 (n) Improvement, RR [CI] Treatment Control Yeramaneni -59% 1.59 [0.94-2.71] 410 (n) 746 (n) Mura (PSM) 21% 0.79 [0.65-0.96] 563 (n) 563 (n) Elhadi (ICU) 7% 0.93 [0.73-1.17] 34/60 247/405 ICU patients Taşdemir 45% 0.55 [0.20-1.55] 5/85 10/94 OT​1 Kuno (PSM) 0% 1.00 [0.86-1.17] 1,593 (n) 7,972 (n) Stolow -519% 6.19 [2.10-18.3] 137 (n) 352 (n) Wagner 70% 0.30 [0.20-0.44] 638 (n) 819 (n) Pahwani (RCT) 11% 0.89 [0.36-2.20] 8/89 9/89 Siraj 36% 0.64 [0.48-0.83] 183/711 122/289 Zangeneh (ICU) 39% 0.61 [0.42-0.90] n/a n/a ICU patients Tau​2 = 0.10, I​2 = 86.0%, p = 0.12 Late treatment 17% 0.83 [0.66-1.05] 230/6,102 388/38,149 17% improvement Mather (PSM) 61% 0.39 [0.20-0.74] 83 (n) 689 (n) Improvement, RR [CI] Treatment Control Yeramaneni 51% 0.49 [0.16-1.52] 351 (n) 6,807 (n) Fung 0% 1.00 [0.96-1.04] population-based cohort Razjouyan 27% 0.73 [0.59-0.92] 93 (n) 9,981 (n) Wallace -11% 1.11 [0.89-1.35] 98/423 1,436/7,521 Tau​2 = 0.04, I​2 = 78.4%, p = 0.16 Prophylaxis 15% 0.85 [0.68-1.06] 98/950 1,436/24,998 15% improvement All studies 17% 0.83 [0.71-0.96] 328/7,052 1,824/63,147 17% improvement 16 famotidine COVID-19 mortality results c19early.com/fm Aug 2022 Tau​2 = 0.05, I​2 = 85.0%, p = 0.011 1 OT: comparison with other treatment Favors famotidine 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+ Pahwani (RCT) 12% 0.88 [0.53-1.45] 21/89 24/89 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.62 Late treatment 12% 0.88 [0.53-1.45] 21/89 24/89 12% improvement All studies 12% 0.88 [0.53-1.45] 21/89 24/89 12% improvement 1 famotidine COVID-19 mechanical ventilation result c19early.com/fm Aug 2022 Tau​2 = 0.00, I​2 = 0.0%, p = 0.62 Favors famotidine 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+ Taşdemir 37% 0.63 [0.28-1.43] 8/85 14/94 OT​1 Improvement, RR [CI] Treatment Control Stolow -2390% 24.90 [3.70-168] 137 (n) 352 (n) Pahwani (RCT) 10% 0.90 [0.51-1.58] 18/89 20/89 Tau​2 = 1.10, I​2 = 83.7%, p = 0.45 Late treatment -70% 1.70 [0.44-6.51] 26/311 34/535 -70% improvement All studies -70% 1.70 [0.44-6.51] 26/311 34/535 -70% improvement 3 famotidine COVID-19 ICU results c19early.com/fm Aug 2022 Tau​2 = 1.10, I​2 = 83.7%, p = 0.45 1 OT: comparison with other treatment Favors famotidine 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+ Samim.. (SB RCT) 33% 0.67 [0.45-0.98] hosp. time 10 (n) 10 (n) Improvement, RR [CI] Treatment Control Taşdemir 18% 0.82 [0.72-0.93] hosp. time 85 (n) 94 (n) OT​1 Pahwani (RCT) 17% 0.83 [0.79-0.89] hosp. time 89 (n) 89 (n) Tau​2 = 0.00, I​2 = 0.0%, p < 0.0001 Late treatment 17% 0.83 [0.78-0.88] 0/184 0/193 17% improvement Fung 6% 0.94 [0.91-0.97] hosp. population-based cohort Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.00016 Prophylaxis 6% 0.94 [0.91-0.97] 6% improvement All studies 14% 0.86 [0.78-0.95] 0/184 0/193 14% improvement 4 famotidine COVID-19 hospitalization results c19early.com/fm Aug 2022 Tau​2 = 0.01, I​2 = 81.7%, p = 0.0027 1 OT: comparison with other treatment Favors famotidine 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+ Brennan (DB RCT) 48% 0.52 [0.20-1.32] no recov. 5/27 10/28 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.17 Early treatment 48% 0.52 [0.20-1.32] 5/27 10/28 48% improvement Samim.. (SB RCT) 0% 1.00 [0.42-2.40] no recov. 5/10 5/10 Improvement, RR [CI] Treatment Control Taşdemir 20% 0.80 [0.65-0.99] recov. time 85 (n) 94 (n) OT​1 Pahwani (RCT) 10% 0.90 [0.85-0.96] recov. time 89 (n) 89 (n) Tau​2 = 0.00, I​2 = 0.0%, p = 0.00023 Late treatment 10% 0.90 [0.85-0.95] 5/184 5/193 10% improvement Balouch 37% 0.63 [0.26-1.54] recov. time 80 (n) 227 (n) Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.32 Prophylaxis 37% 0.63 [0.26-1.54] 0/80 0/227 37% improvement All studies 11% 0.89 [0.84-0.95] 10/291 15/448 11% improvement 5 famotidine COVID-19 recovery results c19early.com/fm Aug 2022 Tau​2 = 0.00, I​2 = 0.0%, p = 0.00013 1 OT: comparison with other treatment Favors famotidine 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+ Balouch 22% 0.78 [0.36-1.51] symp. case 18/80 49/227 Improvement, RR [CI] Treatment Control Fung -12% 1.12 [1.10-1.15] cases population-based cohort MacFadden 7% 0.93 [0.84-1.03] cases n/a n/a Tau​2 = 0.02, I​2 = 86.0%, p = 0.98 Prophylaxis 0% 1.00 [0.84-1.19] 18/80 49/227 0% improvement All studies 0% 1.00 [0.84-1.19] 18/80 49/227 0% improvement 3 famotidine COVID-19 case results c19early.com/fm Aug 2022 Tau​2 = 0.02, I​2 = 86.0%, p = 0.98 Favors famotidine 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+ Brennan (DB RCT) 48% 0.52 [0.20-1.32] no recov. 5/27 10/28 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.17 Early treatment 48% 0.52 [0.20-1.32] 5/27 10/28 48% improvement Shoaibi -3% 1.03 [0.89-1.18] death 1,816 (n) 26,820 (n) Improvement, RR [CI] Treatment Control Zhou (PSM) -81% 1.81 [1.28-2.58] severe case 72/519 198/2,595 Yeramaneni -59% 1.59 [0.94-2.71] death 410 (n) 746 (n) Mura (PSM) 21% 0.79 [0.65-0.96] death 563 (n) 563 (n) Elhadi (ICU) 7% 0.93 [0.73-1.17] death 34/60 247/405 ICU patients Taşdemir 45% 0.55 [0.20-1.55] death 5/85 10/94 OT​1 Kuno (PSM) 0% 1.00 [0.86-1.17] death 1,593 (n) 7,972 (n) Stolow -519% 6.19 [2.10-18.3] death 137 (n) 352 (n) Wagner 70% 0.30 [0.20-0.44] death 638 (n) 819 (n) Pahwani (RCT) 11% 0.89 [0.36-2.20] death 8/89 9/89 Siraj 36% 0.64 [0.48-0.83] death 183/711 122/289 Zangeneh (ICU) 39% 0.61 [0.42-0.90] death n/a n/a ICU patients Tau​2 = 0.13, I​2 = 89.1%, p = 0.45 Late treatment 9% 0.91 [0.71-1.16] 302/6,621 586/40,744 9% improvement Freedberg (PSM) 57% 0.43 [0.21-0.86] death/int. 8/84 332/1,536 Improvement, RR [CI] Treatment Control Mather (PSM) 61% 0.39 [0.20-0.74] death 83 (n) 689 (n) Balouch 22% 0.78 [0.36-1.51] symp. case 18/80 49/227 Yeramaneni 51% 0.49 [0.16-1.52] death 351 (n) 6,807 (n) Cheung -34% 1.34 [0.24-6.06] severe case 23 (n) 929 (n) Fung 0% 1.00 [0.96-1.04] death population-based cohort Razjouyan 27% 0.73 [0.59-0.92] death 93 (n) 9,981 (n) Wallace -11% 1.11 [0.89-1.35] death 98/423 1,436/7,521 MacFadden 7% 0.93 [0.84-1.03] cases n/a n/a Tau​2 = 0.02, I​2 = 70.2%, p = 0.048 Prophylaxis 13% 0.87 [0.76-1.00] 124/1,137 1,817/27,690 13% improvement All studies 14% 0.86 [0.76-0.97] 431/7,785 2,413/68,462 14% improvement 22 famotidine COVID-19 peer reviewed trials c19early.com/fm Aug 2022 Tau​2 = 0.05, I​2 = 84.2%, p = 0.017 Effect extraction pre-specified(most serious outcome, see appendix) 1 OT: comparison with other treatment Favors famotidine Favors control
Figure 11. 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 12 shows a forest plot for random effects meta-analysis of all studies after exclusions.
[Elhadi], unadjusted results with no group details.
[Fung], not fully adjusting for the different baseline risk of systemic autoimmune patients.
[Taşdemir], excessive unadjusted differences between groups.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Brennan (DB RCT) 48% 0.52 [0.20-1.32] no recov. 5/27 10/28 Improvement, RR [CI] Treatment Control Tau​2 = 0.00, I​2 = 0.0%, p = 0.17 Early treatment 48% 0.52 [0.20-1.32] 5/27 10/28 48% improvement Shoaibi -3% 1.03 [0.89-1.18] death 1,816 (n) 26,820 (n) Improvement, RR [CI] Treatment Control Zhou (PSM) -81% </