Pearlman 1980.

Methods	Design: RCT Study dates: unclear, during 1977 Malaria transmission pattern and local antimalarial drug resistance: "subjects were resident in an area highly endemic for P. vivax and chloroquine resistant P. falciparum" Adverse event monitoring: "a physician visited the study area each week and conducted a sick call for participating and nonparticipating villagers...Between physician visits, residents were taken to a nearby health centre for serious medical problems"
Participants	Number enrolled: 990 Inclusion criteria: "All eligible and consenting villagers over 10 years of age were included in the study" Exclusion criteria: "Female villagers of childbearing age (15‐44 years) were not considered for inclusion" Country of recruitment: The Bhu Phram Valley, Thailand Country of malaria exposure: The Bhu Phram Valley, Thailand Duration of exposure to malaria: study duration 26 weeks Type of participants: Thai residents, semi‐immune
Interventions	1. Mefloquine (1 x 180 mg tablet, children 22 to 35 kg ½ dose) weekly 2. Mefloquine (1 x 360 mg tablet, children 22 to 35 kg ¼ dose) weekly 3. Mefloquine (1 x 360 mg tablet, children 22 to 35 kg ¼ dose) every 2 weeks 4. Placebo (1 x tablet) weekly Co‐interventions: "Those who had experienced falciparum parasitemias were given a therapeutic dose of sulfadoxine (1,500 mg)‐pyrimethamine (75 mg), and those with vivax or malariae parasitemias were treated with the standard regimen of chloroquine (1,500 mg over a 3‐day period), followed by primaquine, 15 mg daily for 14 days, for those study subjects known to be G‐6‐PD normal"
Outcomes	Included in the review: 1. Clinical cases of malaria 2. Episodes of parasitaemia 3. Adverse events; any Outcomes assessed not included in the review: 4. Laboratory tests; haematocrit, white cell count, white cell differential, serum glutamic oxaloacetic transaminase, alkaline phosphatase and blood urea nitrogen
Notes	Funding sources: Not mentioned
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"Assignment to one of six treatment groups was made on a stratified random number basis" Comment: no details of how random numbers were generated
Allocation concealment (selection bias)	Unclear risk	"In the course of this visit, the technician opened a sealed, numbered envelope, gave the enclosed tablets, and observed the subject swallow them" Comment: no mention of the envelope being opaque
Blinding of participants and personnel (performance bias) Adverse effects/events	Low risk	"Each subject received two tablets each week (medication, placebo or a combination) in order to maintain the double blind nature of the study" "All tablets were identical in appearance"
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Comment: described as double blind but not clear how this was achieved
Incomplete outcome data (attrition bias); efficacy	Unclear risk	"Nine hundred and ninety nine subjects began the 25‐week field trial and 856 completed it (86.5%). 160/189 (85%) of the mefloquine 180 mg weekly group, 169/191 (88%) of the mefloquine 360 mg weekly, 158/184 (86%) of the mefloquine 360 mg fortnightly and 36/44 (82%) of the placebo group completed the trial" Comment: reasons for losses to follow‐up were not reported
Incomplete outcome data (attrition bias); safety	Low risk	"There was no clinical evidence of drug toxicity in the 990 study participants, nor were there significant changes in the biochemical parameters"
Selective reporting (reporting bias); efficacy	Low risk	"Table 2 shows the number of subjects in each group who completed the study, the number infected with P. falciparum, and the number of episodes of asexual parasitemia"
Selective reporting (reporting bias); safety	High risk	"There was no clinical evidence of drug toxicity in the 990 study participants" Comment: it was unclear whether all events that occurred during the 6 month trial period were included
Other bias	Unclear risk	Comment: study sponsor not reported