Summary of findings 2. ‘Summary of findings' table 2.

Artemether compared with quinine for treating adults with severe malaria
Patient or population: adults with severe malaria Settings: malaria‐endemic countries Intervention: intramuscular artemether Comparison: intravenous or intramuscular quinine
Outcomes	Illustrative comparative risks* (95% CI)		Relative effect (95% CI)	Number of participants (trials)	Certainty of the evidence (GRADE)	Comments
	Risk with quinine	Risk with artemether
Death	208 per 1000	123 per 1000 (87 to 173)	RR 0.59 (0.42 to 0.83)	716 (4 trials)	⊕⊕⊕⊝ MODERATEa,b,c,d Due to imprecision	Artemether probably reduces the risk of death compared to quinine.
Coma resolution time	‐	‐	Not pooled. Little difference.	657 (2 trials)	⊕⊕⊝⊝ LOWa,e,f,g Due to inconsistency and imprecision	Artemether may make little or no difference to coma resolution time compared to quinine.
Neurological sequelae at discharge	4 per 1000	12 per 1000 (1 to 111)	RR 2.92 (0.31 to 27.86)	560 (1 trial)	⊕⊕⊝⊝ LOWg,h Due to imprecision	Artemether may increase the risk of neurological sequelae compared to quinine. However, the effects vary and it is possible artemether decreases neurological sequelae.
Parasite clearance time	‐	‐	Not pooled. Little difference apparent.	716 (4 trials)	⊕⊕⊕⊝ MODERATEa,c,f,i Due to imprecision	Artemether probably makes no difference to parasite clearance time compared to quinine.
Fever clearance time	‐	‐	Not pooled. Little difference apparent.	716 (4 trials)	⊕⊕⊝⊝ LOWa,c,f,j Due to inconsistency and imprecision	Artemether may make little or no difference to parasite clearance time compared to quinine.
*The assumed risk is the median control group risk across studies. The corresponding risk (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). Abbreviations: CI: confidence interval; RR: risk ratio.
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

^aNo serious risk of bias: trials are generally well conducted and at low risk of bias.
 ^bNo serious inconsistency: statistically significant differences were only seen in one of the four trials. However, statistical heterogeneity between trials was low and the overall meta‐analysis is statistically significant.
 ^cNo serious indirectness: all four trials compared intramuscular artemether with intravenous quinine in adults; two trials from Thailand, one each from Vietnam and Papua New Guinea
 ^dDowngraded by 1 for serious imprecision: these trials, and the overall meta‐analysis are very underpowered to detect a difference in mortality or to prove equivalence.
 ^eHien 1996 and Karbwang 1995 reported median coma time for artemether versus quinine (Hien 1996: 66 versus 48, P = 0.003; Karbwang 1995: 48 versus 48). Downgraded by 1 for inconsistency: one trial found a shorter median coma resolution time with quinine, and one trial found no difference.
 ^fDowngraded by 1 for imprecision: the data could not be pooled.
 ^gNo serious risk of bias: this single trial was at low risk of bias.
 ^hDowngraded by 2 for very serious imprecision: neurological sequelae in adults were uncommon. This trial is underpowered to detect or exclude clinically important differences.
 ⁱTwo trials found no significant difference between parasite clearance time for artemether versus quinine (Karbwang 1992: mean 63.6 versus 61.6, P = 0.85; and Seaton 1998: median 48 versus 52, P = 0.381). Two other trials reported significantly shorter median parasite clearance times for artemether versus quinine (Hien 1996: 72 versus 90, P < 0.001 and Karbwang 1995: 54 versus 78, P = 0.007). No serious inconsistency: The two largest trials both found shorter median clearance times with artemether.
 ^jThree trials reported median fever clearance time for artemether versus quinine (127 versus 90, P < 0.001; 32 versus 48, P =  0.034 and 79 versus 84, no significant difference) (Hien 1996, Seaton 1998 and Karbwang 1995). Karbwang 1992 reported mean fever clearance time and found a statistically significant reduction of about 30 hours with artemether. Downgraded by 1 for inconsistency: One trial found a shorter median fever clearance time with quinine, and two trials found a shorter time with artemether.