Smithuis 2006 MMR.

Methods	Trial design: A 4‐arm open‐label RCT Follow‐up: A symptom questionnaire, malaria film, and gametocyte count on days 0, 1, 2, 3, 7, 14, 21, 28, 35, and 42. Hb was measured on days 0 and 28. Adverse event monitoring: A symptom questionnaire at each visit
Participants	Number of participants: 652 Inclusion criteria: Age > 1 year, axillary temperature > 37.5 °C or history of fever in the previous 48 hrs, P. falciparum mono‐infection 500 to 100,000 parasites/µL or co‐infection with P. vivax, informed consent. Exclusion criteria: Pregnancy, signs of severe malaria, signs or symptoms of other diseases, history of taking mefloquine in the previous 2 months or any other antimalarial in the previous 48 hrs, history of psychiatric disease.
Interventions	1. DHA‐P, fixed dose combination, 40 mg/320 mg tablets (Artekin: Holleykin) Total dose: DHA 6.3 mg/kg + P 50.4 mg/kg in 3 divided doses, given once daily for 3 days Supervised 2. DHA‐P, fixed dose combination, 40 mg/320 mg tablets (Artekin: Holleykin) Total dose: DHA 6.3 mg/kg + P 50.4 mg/kg in 3 divided doses, given once daily for 3 days Unsupervised 3. Artesunate plus mefloquine, loose combination (artesunate: Guilin, Lariam: Hoffman‐La Roche) AS 4 mg/kg once daily for 3 days MQ 25 mg base/kg as a single dose on day 0 Supervised 4. Artesunate plus mefloquine, loose combination (artesunate: Guilin, Lariam: Hoffman‐La Roche) AS 4 mg/kg once daily for 3 days MQ 25 mg base/kg as a single dose on day 0 Unsupervised
Outcomes	Failure Rate at days 42 and 28, 42 PCR‐unadjusted and PCR‐adjusted P. vivax during follow‐up and median time to appearance Gametocyte carriage at days 0, 7, 14, 21, and 28 Mean change in Hb from day 0 to day 28 Adverse events Not included in the review: Fever clearance Parasite clearance New gametocyte appearance at day 7 and day 14
Notes	Country: Myanmar Setting: Rural village tracts Transmission: Seasonal with peaks in the monsoon season Nov to Jan and sometimes in the early monsoon, May to June Resistance: Very high rates of CQ and SP resistance Dates: Nov 2003 to Feb 2004 Funding: Médecins sans Frontières (Holland)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Unmarked and sealed envelopes, containing the treatment allocation were drawn from a box.
Allocation concealment (selection bias)	Unclear risk	"Unmarked and sealed envelopes". No further details given.
Blinding for microscopy outcomes (performance bias and detection bias)	Unclear risk	No comment on blinding of laboratory staff.
Blinding for adverse events (performance and detection bias)	High risk	An open label trial.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Very low losses to follow‐up in both groups.
Selective reporting (reporting bias)	Low risk	The WHO recommends 63 days follow‐up in studies of AS+MQ. Day 42 outcomes are likely to overestimate the efficacy of the two drugs.
Other bias	Low risk	No other sources of bias identified.