Table 2.
GRADE recommendation for outcomes evaluated for the use of HCQ/CQ in patients with COVID-19 infection caused by SARS-CoV-2
| Certainty assessment | No of patients | Effect | Certainty, Importance | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| No of studies; Study design | Risk of bias | Inconsistency | Indirectness | Imprecision | Other considerations | Efficacy Outcomes | Placebo | Relative (95% CI) | Absolute (95% CI) | |
| Virological Cure (RT-PCR negative) | ||||||||||
| 6 RCT | seriousa,b | not seriousc | not serious | not serious | none | 293/340 (86.2%) | 233/305 (76.4%) | OR 2.08 (1.36-3.17) | 107 more per 1,000 (from 51 more to 147 more) | ⨁⨁⨁◯ MODERATE CRITICAL |
| Mortality | ||||||||||
| 10 OS; 5 RCT | seriouse | seriousf | not serious | seriousg | none | 840/4612 (18.2%) | 1319/6422 (20.5%) | OR 0.98 (0.70-1.37) | 3 fewer per 1,000 (from 52 fewer to 56 more) | ⨁◯◯◯ VERY LOW CRITICAL |
| Radiological Cure (CT scan) | ||||||||||
| 2 RCT | not serious | not serious | not serious | seriousd | none | 35/41 (85.4%) | 26/43 (60.5%) | OR 3.89 (1.35-11.23) | 251 more per 1,000 (from 69 more to 340 more) | ⨁⨁⨁◯ MODERATE IMPORTANT |
| Progression - ICU admission/Intubation/Severe Illness/CTprogression | ||||||||||
| 6 OS; 3 RCT | seriouse | seriousf | not serious | not serious | none | 383/1646 (23.3%) | 229/1627 (14.1%) | OR 1.77 (1.46-2.13) | 84 more per 1,000 (from 52 more to 118 more) | ⨁⨁◯◯LOW CRITICAL |
| Hospital Discharge | ||||||||||
| 4 OS; 1 RCT | seriouse | seriousf | not serious | not serious | none | 829/1234 (67.2%) | 824/1104 (74.6%) | OR 0.64 (0.53-0.78) | 93 fewer per 1,000 (from 137 fewer to 50 fewer) | ⨁⨁◯◯ LOW IMPORTANT |
| Prolong QT interval | ||||||||||
| 3 OS | not serioush | not serious | not serious | not serious | strong association | 49/347 (14.1%) | 3/278 (1.1%) | OR 11.15 (3.95-31.44) | 98 more per 1,000 (from 31 more to 245 more) | ⨁⨁⨁⨁ HIGH CRITICAL |
| Mortality (HR) | ||||||||||
| 5 OS | not seriousi | not seriousj | not serious | seriousg | none | -/0 | -/0 | HR 1.05 (0.86-1.29) | 1 fewer per 1,000 (from 1 fewer to 1 fewer) | ⨁⨁⨁◯ MODERATE CRITICAL |
CI: Confidence interval; OR: Odds ratio; HR: Hazard Ratio; RCT - Randomized control trials; OS - Observational study. aHuang et al. and Chen J et al. have some concerns with randomization concealment, which will affect the virological cure estimate, hence downgraded for quality of evidence. bConfounding in all three studies, along with missing data (Huang M et al.) and selection of patients (Mallal et al.) may affect the estimate. Studies have serious overall ROB, hence downgraded for evidence. cAlthough I2 >40%, but exclusion of Mallat et al. (moderate selection bias) resulted in I2=0% without change in overall effect estimate. Hence heterogeneity ignored. d1. The Optimal Information Size (OIS) is 245 patients in each group, which was not met in the outcome. OR 2. Effect estimate 95% Confidence interval (CI) includes one. OR Both of the above reasons hence downgraded for Imprecision. eRCT’s have a negligible contribution to the overall effect estimate and observational studies have moderate to serious ROB for unadjusted mortality rate, progression of disease, hospital discharge. Hence downgraded for overall ROB. fAs I2 >50%. Hence, Quality of evidence downgraded for heterogeneity. gAs 95% CI includes one, hence downgraded for imprecision. h. Studies have low to moderate ROB, hence not downgraded. i. Adjusted Hazard ratios (HR) was presented by all the authors. Adjustment of all the covariates which might have led to the variability in mortality or cardiac arrest has been adjusted during analysis for mortality or cardiac arrest. Hence, not downgraded for risk of bias. jAlthough I2 >40%. sensitivity analysis with exclusion of study done by Yu et al. resulted in I2=31% (<40%) without a change in overall mortality estimate. Only Yu et al. have concluded decrease mortality with the use of HCQ/CQ, hence heterogeneity was ignored