Boudreau 1993.

Methods	Design: RCT Study dates: not mentioned Malaria transmission pattern and local antimalarial drug resistance: not applicable Adverse event monitoring: "At each visit, the subject answered two computerised questionnaires (the Environmental Symptoms Questionnaire and the Profile of Mood States) [and] a physician interview was performed"
Participants	Number enrolled: 359 Inclusion criteria: "males at least 18 years old, met military weight standards, were available for weekly administration of medications and monitoring during the 13 week study period, and were willing to give informed consent" Exclusion criteria: "treatment with beta‐blocking agents or other cardiotropic drugs, underlying chronic disease, history of cardiac arrhythmia, medical history of psychiatric or neurological problems within the last 5 years, anaemia or impaired hepatic or renal function. Women were excluded from participation in the study due to the risk of teratogenicity involved when the drug is used in early pregnancy" Country of recruitment: USA Country of malaria exposure: not applicable Duration of exposure to malaria: not applicable Type of participants: military, non‐travellers
Interventions	1. Mefloquine (1 x 250 mg tablet), larium 228 mg base (F Hoffman La Roche) weekly for 11 weeks 2. Mefloquine (1 x 250 mg tablet), larium 228 mg base (F Hoffman La Roche) weekly for 11 weeks, with loading dose of 1 x 250 mg tablet daily for 3 days during the first week 3. Chloroquine (1 x 300 mg tablet), 300 mg base (F Hoffman La Roche) weekly for 11 weeks
Outcomes	Included in the review: 1. Adverse events; nausea, vomiting, abdominal pain, diarrhoea, headache, dizziness, abnormal dreams, insomnia 2. Adverse events; other (irritability, poor concentration, anger, moodiness, abdominal distension, anorexia, environmental symptoms questionnaire (ESQ), sleep assessment, Profile of Mood States questionnaire) Outcomes assessed not included in the review: 3. Laboratory tests: haemoglobin, haematocrit, platelets, white blood cell count, alanine aminotransferase, blood urea nitrogen and creatinine 4. Analysis of the dizziness index on the ESQ 5. Spontaneous comments on the ESQ (data provided on aggregate)
Notes	Funding sources: Not mentioned
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"...military personnel were assigned to drug groups in a ratio of approximately 3:3:1…stratification was performed by major subordinate command so that equal proportions of each study group would be represented in each MSC" Comment: not mentioned how the randomisation code was generated
Allocation concealment (selection bias)	Unclear risk	Comment: method allocation concealment not mentioned
Blinding of participants and personnel (performance bias) Adverse effects/events	Low risk	"...the ‘double dummy’ method of blinding was employed with either chloroquine or mefloquine placebos administered with active drug… In addition, during the first week of the study, on days two and three, a single mefloquine tablet or placebo was administered. Both drugs and placebos had an extremely bitter taste... identical placebo tablets"
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Comment: described as double blind but no description provided of how this was achieved for researchers and outcome assessors
Incomplete outcome data (attrition bias); efficacy	Unclear risk	N/A
Incomplete outcome data (attrition bias); safety	Unclear risk	Comment: 15 medical withdrawals are reported within the study. It is unclear whether these are the only losses to follow up which occurred, or whether they occurred in the mefloquine loading dose group or weekly administration group.
Selective reporting (reporting bias); efficacy	Unclear risk	N/A
Selective reporting (reporting bias); safety	High risk	‘table 5 outlines the percent of the group with symptoms only when significance was demonstrated’ ‘selected haematology and biochemistry tests were performed… no significant differences were noted among the three drugs when comparing the mean values’ Comment: data is not fully reported for ‘other symptoms’; only significant results are reported for the ESQ, and data for spontaneous comments on the ESQ are not reported; data is not fully reported for the POMS.
Other bias	Unclear risk	Comment: study sponsor not mentioned, but the lead author is attributed to ‘Pharmaceutical Systems Incorporated’