Placebo-control

CORRECT

The primary aim of the study is to assess efficacy of a new drug therapy for fatigue. The gold standard is a randomized controlled trial. Although other drugs are used to treat fatigue in the clinical setting, there is no uniformly accepted pharmacotherapy for this condition and there are too few studies of other drugs to consider an established treatment. The best approach, therefore, would be to compare modafinil with placebo using a double-blind approach. If an investigator believed that the evidence in favor of other psychostimulants, such as methylphenidate, were sufficiently strong, the trial could be designed as a comparison of methylphenidate (the active control) vs. modafinil. In this case, the investigator must be concerned about a finding of "no difference" in a two-arm trial. To avoid this, either a placebo arm or multiple doses of the methylphenidate, or both, could be added to include a measure of the study's sensitivity. These additional study arms would also provide comparative data for judging the magnitude of the effect of the modafinil, at the doses studied.