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.