Summary of findings 1. Favipiravir versus no treatment, supportive treatment, or other antiviral treatment for treating COVID‐19.
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Patient/population: people with confirmed COVID‐19 Setting: both inpatient and outpatient Intervention: favipiravir Comparison: no treatment, supportive treatment, or any other experimental antiviral treatment (i.e. any other treatment not containing favipiravir) | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk without favipiravir | Risk with favipiravir | |||||
| All‐cause mortality – at 28 to 30 days, or in‐hospital | 50 per 1000 | 42 per 1000 (24 to 73) | RR 0.84 (0.49 to 1.46) | 3459 (11 RCTs) | ⨁◯◯◯ Very lowa,b,c | We are uncertain whether favipiravir reduces all‐cause mortality (at 28 to 30 days, or in‐hospital). |
| Progression to invasive mechanical ventilation | 80 per 1000 | 68 per 1000 (54 to 87) | RR 0.86 (0.68 to 1.09) | 1383 (8 RCTs) | ⨁◯◯◯ Very lowc,d,e | We are uncertain whether favipiravir reduces the progression to invasive mechanical ventilation. |
| Need for admission to hospital (if ambulatory) | 92 per 1000 | 96 per 1000 (41 to 227) | RR 1.04 (0.44 to 2.46) | 670 (4 RCTs) | ⨁⨁◯◯ Lowc,f | Favipiravir may make little to no difference in the need for admission to hospital (if ambulatory). |
| Time to clinical improvement (defined as time to a 2‐point reduction in patients’ admission status on WHO’s ordinal scale) | ‐ | ‐ | HR 1.13 (0.69 to 1.83) | 721 (4 RCTs) | ⨁◯◯◯ Very lowg,h,i | We are uncertain whether favipiravir reduces the time to clinical improvement (defined as time to a 2‐point reduction in patients’ admission status on WHO’s ordinal scale). |
| Progression to oxygen therapy | 158 per 1000 | 189 per 1000 (131 to 276) | RR 1.20 (0.83 to 1.75) | 543 (2 RCTs) | ⨁⨁◯◯ Lowc,e,j | Favipiravir may make little to no difference in progression to oxygen therapy. |
| All adverse events | 180 per 1000 | 228 per 1000 (194 to 286) | RR 1.27 (1.05 to 1.54) | 4699 (18 RCTs) | ⨁⨁◯◯ Lowk,l,m | Favipiravir may result in an increased risk of an adverse event. |
| Serious adverse events attributable to the drug | 43 per 1000 | 45 per 1000 (33 to 61) | RR 1.04 (0.76 to 1.42) | 3317 (12 RCTs) | ⨁⨁◯◯ Lowc,e,n | Favipiravir may result in little to no difference in serious adverse events attributable to the drug. |
| *The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; HR: hazard ratio; RCT: randomized controlled trial; RR: risk ratio; WHO: World Health Organization | ||||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. | ||||||
aDowngraded by one level for risk of bias (RoB): we had some concerns for risk of bias for Ivaschenko 2020 and Solaymani‐Dodaran 2021, and Finberg 2021; Mahmudie 2022; Tabarsi 2021 had a high RoB. bDowngraded by one level for inconsistency, as we identified moderate heterogeneity (I² = 54%). cDowngraded by one level for serious imprecision: the lower CI bound represents an important benefit from favipiravir, whereas the upper bound includes harm. dDowngraded by two levels for RoB, as Ivaschenko 2020, Ruzhentsova 2021, and Solaymani‐Dodaran 2021 had some concerns in the risk of bias assessment, and Mahmudie 2022, Finberg 2021, and Lou 2020 had high RoB. eNot downgraded for inconsistency as we did not identify any heterogeneity (I² = 0%). fDowngraded by one level due to inconsistency, as we identified moderate heterogeneity (I² = 57%). gDowngraded by one level for serious risk of bias. We deemed Finberg 2021 to have a high risk of bias arising from the randomization process and some concerns for bias due to deviations from the intended interventions; we had some concerns for risk of bias for Ruzhentsova 2021 due to measurement of outcome, and some concerns for Udwadia 2020 due to missing outcome data. hDowngraded two levels due to inconsistency, as we identified considerable heterogeneity (I² = 73%). iDowngraded by one level for serious imprecision: the lower CI bound represents mild harm from favipiravir, whereas the upper bound includes appreciable benefit. jDowngraded by one level for serious RoB: we deemed Lou 2020 to have a high RoB for randomization and some concerns due to deviations from intended interventions. kDowngraded by one level for RoB as Balykova 2020, Luvira 2023, Sirijatuphat 2022, Ruzhentsova 2021, Shinkai 2021, Chen 2021, and Finberg 2021 account for nearly 50% of the weight in the meta‐analysis and have a high RoB, but sensitivity analysis removing these studies resulted in a similar pooled estimate and CI. lDowngraded by one level for inconsistency, as we identified considerable heterogeneity (I² = 64%). mNot downgraded for imprecision, even though the CI varies from 1.08 to 1.59 because the upper and lower bounds point towards harm from the intervention. nDowngraded by one level for RoB: we had some concerns for risk of bias for Holubar 2021, Shah 2023, Shenoy 2021, Udwadia 2020, and Zhao 2021, and deemed Balykova 2020, Finberg 2021, Lou 2020, Luvira 2023, Ruzhentsova 2021, and Shinkai 2021 to have a high RoB.