Smithuis 2010

Methods	Individually RCT (5 comparisons - 10 arms). Follow-up: Patients were asked to return weekly for 9 weeks for assessment and at any other time they were unwell. Dates: December 2008 to March 2009.
Participants	Number: 808 people attending clinics in Myanmar. Inclusion criteria: Age = 6 months, weight = 5 kg, P. falciparum mono-infection 500 to 200,000 parasites/µL or co-infection with P. vivax, informed consent. Exclusion criteria: Pregnancy, signs of severe malaria, severe malnutrition, history of hypersensitivity to any of the trial drugs, severe malnutrition, concomitant febrile illness, history of psychiatric disorder, a full course of MQ in the previous nine weeks or any other antimalarial in the previous 48 hrs.
Interventions	Each of the five trial arms was divided into two where one half also received a one-off dose of 0.75 mg/kg PQ on day 1. Groups: 1+2. AS plus amodiaquine, fixed-dose combination: 25 mg/67.5 mg or 50 mg/135 mg or 100 mg/270 mg tablets. • AS 4 mg/kg once daily for 3 days 1. AQ 10.8 mg base/kg once daily for 3 days 3+4. AL, fixed-dose combination: 20 mg/120 mg tablets. • A 3.3 mg/kg in two divided doses each day for 3 days • L 19.8 mg/kg in two divided doses each day for 3 days • Advised to consume fatty food or breast feed before each dose 5+6. AS plus MQ, fixed-dose combination: 25 mg/55 mg or 100 mg/220 mg tablets (artesunate: Guilin, Lariam: Hoffman-La Roche) • AS 4 mg/kg once daily for 3 days • MQ 8.8 mg/kg once daily for 3 days 7+8. Artesunate plus MQ, 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 1 (reported as day 0) 9+10. DHAP, fixed-dose combination: 40 mg/320 mg or 20 mg/160 mg tablets (Artekin: Holleykin) • DHA 2.5 mg/kg once daily for 3 days • P 20 mg/kg once daily for 3 days First dose supervised, all others unsupervised.
Outcomes	1. Recurrent parasitaemia at day 15, 29, 43 and 64 (reported as days 14, 28, 42 and 63) 2. Treatment failure due to P. falciparum 3. Gametocytaemia prevalence 4. Person-gametocyte weeks 5. Haemoglobin on days 1 and 64 6. Adverse events (monitoring not described)
Notes	Funding: Médecins sans Frontières (Holland).
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"After patients were screened and enrolled in the study, they were stratified prospectively into three age groups (1 to 4 years, 5 to 14 years and older than 14 years). Patients were randomly assigned in equal numbers to receive one of the five different treatments. They were then randomly assigned either a single dose of PQ …or not".
Allocation concealment (selection bias)	Low risk	"Treatment allocations were put in sealed envelopes in blocks of 50 for each age group, and random assignment was achieved by patients drawing an envelope from a box after enrolment. When the box was empty, another 50 envelopes were added".
Incomplete outcome data (attrition bias) All outcomes	Low risk	Attrition is low in absolute numbers and unlikely to have introduced significant bias.
Selective reporting (reporting bias)	Low risk	No evidence of selective reporting.
Other bias	Low risk	No indication of other bias.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open label trial for patients and medical staff.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Microscopists were blinded.