A review of the quality of randomized clinical trials of adjunctive therapy for the treatment of cerebral malaria.

BACKGROUND: Randomized controlled clinical trials (RCTs) of adjunctive treatment to reduce the high-mortality associated with cerebral malaria (CM) have so far failed to show any benefit. This may be due in part to improperly designed and/or conducted trials. Therefore a systematic review of quality of RCTs for the treatment of CM with mortality as either primary or secondary outcome published between 1980 and 2000, was conducted.
METHODS: RCTs from the peer-reviewed literature using electronic searches. Methodological quality was assessed using an individual component approach (adequacy of concealment of allocation schedule, generation of allocation sequence, double blinding and analysis of participant as randomized). Sample sizes were recalculated for the ability of reviewed trials to detect 25% and 50% reductions in mortality.
RESULTS: Nine trials satisfied the inclusion criteria and were reviewed. Only two had sufficient power to detect a 50% reduction in mortality, and none could detect a 25% reduction. All the trials had inadequate methodological quality in one or more of the components, although in two trials these deficiencies were few.
CONCLUSION: There is a need for researchers and donors to ensure proper planning and implementation of RCTs in developing countries. In CM, demonstration of worthwhile reduction in mortality by a single intervention will require a large number of subjects, which a single centre may not be able to recruit.