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Table 2 Summary of findings according to GRADE approach. CQ/HCQ compared to Placebo or no CQ/HCQ for malarial and non-malarial conditions

From: Systematic review and meta-analysis of the safety of chloroquine and hydroxychloroquine from randomized controlled trials on malarial and non-malarial conditions

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect

(95% CI)

№ of participants

(studies)

Certainty of the evidence

(GRADE)

Comments

Risk with placebo/non-comparator

Risk with HCQ/CQ

SAE

14 per 1.000

15 per 1.000

(12 to 20)

OR 0.98 (0.76 to 1.26)

15942

(33 RCTs)

MODERATE a

CQ/HCQ likely does not increase SAE.

Retinopathy

18 per 1.000

28 per 1.000

(7 to 105)

OR 1.63

(0.40 to 6.57)

344

(5 RCTs)

LOW b

The evidence is very uncertain about the effect of CQ/HCQ on retinopathy.

Cardiac Complications

20 per 1.000

37 per 1.000

(25 to 55)

RR 1.62

(1.10 to 2.38)

9908

(16 RCTs)

MODERATE c

CQ/HCQ may result in an increase in cardiac complications.

  1. *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI confidence interval, OR odds ratio, RR risk ratio, SAE serious adverse events, CQ chloroquine; HCQ hydroxychloroquine, GRADE Grading of Recommendations Assessment, Development, and Evaluation
  2. GRADE levels of evidence
  3. High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
  4. 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
  5. Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
  6. 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
  7. Explanations
  8. aThe quality of evidence was rated down due to non-inclusion of unpublished data
  9. bConsidering a prevalence of 7.8% of retinopathy in non-diabetic population (Klein,1992), and a 1% of retinopathy risk in the first 5 years of HCQ treatment (Petri 2020), the minimum sample size required for detection of this outcome is 4533 (level of significance =5%; power=1- β=80%). Then, the optimal information size criterion was not met, and the confidence interval was wide. Because of this the quality of evidence was rating downed for imprecision
  10. cThe open-label RCTs were graduated as some concerns of risk of bias due to no information if participants of both groups were submitted to the same method and frequency of the outcome evaluation