Question 14.1

You are seeking a grant to perform a controlled trial of the new psychostimulant, modafinil, as a potential treatment for chronic cancer-related fatigue. Limited anecdotal experience has suggested that the drug can be beneficial and well tolerated, even in a population with advanced illness. You wish to design a study that assesses efficacy as the primary outcome and also provides information about the elements of fatigue that might respond best, the occurrence of other effects (both positive and negative), and the durability of effects over time. You would also like to clarify the nature of a dose-response relationship for fatigue-related outcomes, if this exists. There are numerous methodologies that could be proposed. Consider the following elements of a protocol.

Title: A controlled trial of the psychostimulant, modafinil, for the treatment of chronic cancer-related fatigue

Specific Aims:

Study Design

This study will use a randomized, double-blind, placebo-controlled parallel group design. The duration of the trial will be four weeks and will involve three study visits.

Discussion: Now consider an alternative design: this study will use a randomized, double-blind, parallel group methodology to compare modafinil, the study drug, with methylphenidate, an active control. The duration of the trial will be four weeks and will involve three study visits. Which design, the one that uses placebo-control or the active control, is best?

	Placebo-control
	Active control

Discussion: Now consider yet another alternative design: this study will use a randomized, double-blind, cross-over methodology to compare modafinil, the study drug, with placebo. The duration of the trial will be eight weeks and will involve six study visits. Which design, the one that uses cross-over method or parallel group method, is best?

	Cross-over method
	Parallel group method