Valecha 2010 AS.

Methods	Trial design: An open‐label (non‐inferiority) RCT Follow‐up: Particiopants were managed as outpatients unless local practice dictated otherwise (some centres used hospital stays of between 3 and 28 days). Outpatients were asked to return on days 1, 2, 3, 7, 14, 21, 28, 35, 42, 49, 56, and 63, and any time they felt unwell. Blood smears were performed at each visit. Adverse event monitoring: Blood and urine samples were taken for analysis on days 0, 28, 63 (if abnormal on day 28) and on the day of any recurrent parasitaemia. Twelve‐lead ECGs were performed at days 0, 2, 7, 28 (if abnormal on day 7), 63 and on the day of any recurrent parasitaemia.
Participants	Number of participants: 1150 Inclusion criteria: Age 3 months to 65 years (≥18 years in India), P. falciparum mono‐infection (80 to 200,000 parasites/µL) or mixed infection, weight ≥ 5 kg, fever (≥ 37.5 °C) or history of fever, informed consent. Exclusion criteria: Severe malaria, treatment with MQ in the 60 days before screening, treatment with DHA‐P in the 3 months before screening, > 4% parasitised red blood cells, pregnancy or lactation.
Interventions	1. DHA‐P, fixed dose combination, adult tablets 40 mg/320 mg, child tablets 20 mg/160 mg (Eurartesim®: Sigma Tau) One dose daily for 3 days 2.25 mg/kg DHA and 18 mg/kg piperaquine per dose Dose rounded up to the nearest half tablet 2. Artesunate plus mefloquine, loose dose combination, AS 50mg tablets, MQ 250 mg tablets (Mepha Ltd) AS 4mg/kg once daily for 3 days MQ none on day 0, then 15 mg/kg once on day 1 and 10 mg/kg once on day 2 All doses supervised.
Outcomes	Cure rate at days 28, 42, and 63, PCR corrected and uncorrected Mean change in Hb day 0 to day 63 Gametocyte carriage Person‐gametocyte‐weeks Adverse events Not included in this review: Fever clearance Parasite clearance
Notes	Country: Thailand (six sites), Laos (two centres), and India (three centres). Setting: Hospitals and research units. Transmission: Varied across trial regions. Trial regions in Thailand had unstable, low and seasonal malaria transmission; trial regions in Laos had seasonal transmission with a peak just after the heavy rainy months of July to August; trial regions in India included areas with perennial transmission, perennial transmission with a seasonal peak from June to September, and transmission active in post monsoon months. Resistance: All sites had notable CQ resistance (estimates of 28 day treatment failure at the Indian sites ranged from 32% to 67% between 2002 and 2007). The Thai sites also had multi‐drug resistant P. falciparum. Dates: Jun 2005 to Feb 2007. Funding: Medicines for Malaria Venture, Sigma Tau, and Oxford University.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"The randomisation list was generated by an external contract research organisation (MDS Pharma Services) using the plan procedure of SAS (Cary, NC, USA)".
Allocation concealment (selection bias)	Unclear risk	"Randomisation was conducted under blinded conditions: the blind to the investigator and patient in the randomisation process was maintained by the use of sealed envelopes". Envelopes are not described as opaque.
Blinding for microscopy outcomes (performance bias and detection bias)	Low risk	"Evaluation of the PCR test results was blinded".
Blinding for adverse events (performance and detection bias)	High risk	Trial is described as "open label".
Incomplete outcome data (attrition bias) All outcomes	Low risk	Proportion of participants not completing the trial was low in both groups (6.6% DHA‐P versus 6.0% AS+MQ).
Selective reporting (reporting bias)	Low risk	All listed outcomes reported.
Other bias	High risk	"A committee representing members of the DHA‐PQP Joint Development Team and trial site Principal Investigators developed the protocol. Sigma Tau conducted the study, collected and analysed data. All authors had access to the primary data and take responsibility for data reporting accuracy and completeness. The corresponding author had responsibility for the final decision to submit for publication".