Ringwald 1996.

Methods	RCT Duration: 1 year, 1 month: April 1994 to May 1995
Participants	Adults (> 15 years) with P falciparum malaria Number: 96 Inclusion criteria: fever or history of fever within 24 hours Exclusion criteria: severe/complicated malaria; mixed Plasmodium infection; recent self‐medication; pregnancy Diagnosis: thin film microscopy of P falciparum (asexual parasite density > 5000/µL blood)
Interventions	Pyronaridine: 32 mg/kg in divided doses over 3 days: 16 mg/kg on day 0; 8 mg/kg on days 1 and 2 Chloroquine: 25 mg/kg in divided doses over 3 days: 10 mg/kg on days 0 and 1; 5 mg/kg on day 2
Outcomes	Adverse events Fever clearance (time from onset of treatment until temp remained below 37.5°C)* Parasite clearance (time until the first negative tick blood smear, with subsequent smears negative)* Early treatment failure* Parasitaemia on day 14* Gametocyte carriage at day 14* In vitro drug susceptibility* *Not assessed in quantitative synthesis in this review
Notes	Location: Cameroon Setting: dispensary (outpatients) Malaria endemicity: high Resistance profile: 57% of isolates chloroquine‐resistant Source of funding: French Ministere de la Co‐operation (Grant 93A43); pyronaridine was supplied by the Institute of Parasitic Diseases, Chinese Academy of Preventive Medicine, Shangai, China Follow‐up: 14 days
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Block randomization (blocks of 10); from communication with authors recorded by previous version of this review
Allocation concealment (selection bias)	Low risk	Central randomization; from communication with authors recorded by previous version of this review
Blinding (performance bias and detection bias) All outcomes	Low risk	Blinded, but tablets were different and patients treated with chloroquine suffered pruritis; from communication with authors recorded by previous version of this review
Incomplete outcome data (attrition bias) All outcomes	Low risk	Report lists reasons for attrition and exclusions; unlikely to have differentially influenced liver toxicity outcomes used in this review
Selective reporting (reporting bias)	Low risk	Trial not prospectively registered, trial protocol not available. However, all outcomes stated in methods reported
Other bias	Low risk	None identified
Adverse event monitoring (detection bias) Adverse Events	Unclear risk	Authors do not fully describe method for detection of adverse events. Authors do not give definitions of all adverse events
Incomplete adverse event reporting (reporting bias) Adverse events	Unclear risk	Authors give brief narrative description of adverse events only. Report does not detail extent of elevation in liver transaminases or the proportions retested at day 14