Boudreau 1991.
| Methods | Design: RCT Study dates: July 1983 to March 1984 Malaria transmission pattern and local antimalarial drug resistance: "in this area we believe the efficacy of chloroquine prophylaxis at the time of the study was negligible" Adverse event monitoring: "at each 2 week visit… history of symptoms over the previous fortnight was obtained. Patients were asked about fever, chills, headache, nausea, vomiting, diarrhoea, anorexia, rash, myalgia and dysuria or abnormally coloured urine". Laboratory studies were performed at baseline and at 6 weeks in participants who had not developed malaria |
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| Participants | Number enrolled: 501 Inclusion criteria: "Only males 21 years of age or over were accepted" Exclusion criteria: "All participants were required to have a negative malaria smear (after examination of 200 fields on thick smear) on entry into the study". "...the use of other antimalarials or antibiotics" Country of recruitment: Cambodia Country of malaria exposure: Cambodia Duration of exposure to malaria: ongoing in semi immune population, 14 week study period Type of participants: Thai gem miners with a degree of immunity |
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| Interventions |
Included in review comparisons: 1. Mefloquine (2 x 250 mg tablet) fortnightly for 14 weeks* 2. Chloroquine (1 x 300 mg tablet) weekly* Not included in review comparisons: 3. Fansidar (2 x 500 mg sufadoxine and 25 mg pyrimethamine) fortnightly and chloroquine (1 x 300 mg tablet) weekly* *matched placebo for each treatment arm |
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| Outcomes |
Included in the review: 1. Clinical cases of malaria 2. Adverse events; other (myalgias, rash) Outcomes assessed not included in the review: 3. Laboratory tests; haematocrit, complete blood count, transaminase levels, total and direct bilirubin, alkaline phosphatase, blood urea nitrogen 4. Adverse events; headache, anorexia, fever, chills, nausea, diarrhoea or vomiting (data provided on aggregate) |
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| Notes | Funding sources: Support for this study was from the USA Army Medical Research and Development Command | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | "Assignment… is a 4:3:2 ratio" Comment: method of sequence generation not reported |
| Allocation concealment (selection bias) | Unclear risk | Comment: no details of allocation concealment were reported |
| Blinding of participants and personnel (performance bias) Adverse effects/events | Unclear risk | "Every two weeks in a double blind fashion one of the investigators administered five tablets to each subject" Comment: not mentioned whether placebo tablets had an identical appearance |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | Comment: described as double blind but no mention of how this was achieved for researchers and outcome assessors |
| Incomplete outcome data (attrition bias); efficacy | Unclear risk | "Only 194 patients completed the study until positivity or end of the 14 weeks observation period". "Therefore of the original 501 enrollees, 63 were discarded due to positivity at week 0 and 104 were discarded since they never returned beyond week 0". Comment: Losses to follow‐up during the study was not reported across groups |
| Incomplete outcome data (attrition bias); safety | Unclear risk | "Only 194 patients completed the study until positivity or end of the 14 weeks observation period...Any subject missing one appointment was excluded from the study though each subject's records up to the time of exclusion were entered into the survival analysis...After 3 weeks post treatment and a negative malaria smear some patients wishing to continue were reentered under a new study number and were assigned a double blind randomized treatment" |
| Selective reporting (reporting bias); efficacy | Unclear risk | Comment: number of people contracting malaria in each group and person‐weeks in the study were reported |
| Selective reporting (reporting bias); safety | Unclear risk | "There were no significant differences in frequency of complaints among the study groups for headache, anorexia, fever, chills, nausea, diarrhoea, or vomiting". Comment: Data for specific adverse events not reported. Methods section states participants were asked about dysuria and abnormally coloured urine, but this was not reported in the results |
| Other bias | Low risk | Support for this study was from the USA Army Medical Research and Development Command |