This column reviews the development of intranasal esketamine with particular emphasis on the consistency of the clinical trial results. In the process, it illustrates methodological issues important in the approval process by an agency such as the United States Food and Drug Administration. Topics covered include the importance of study design, the nature of the comparator, and the prespecified statistical analysis plan. The column also discusses what is considered a positive versus a supportive study and the differences between phase 2 and phase 3 studies and the rationale for including both in the development process. While this information is particularly germane to intranasal esketamine, it also serves as a more general example of the drug development and approval process.
Sheldon H Preskorn