Assessing onset of treatment benefit in depression and anxiety: conceptual considerations

Methods for characterizing the onset of treatment benefit in major depressive disorder and generalized anxiety disorder have been studied for some time, yet there is no universal agreement as to the best approaches. Our purpose is to summarize the conceptual framework underlying modern methods for characterizing onset and detailed approaches for which there is consensus from the perspective of a clinician, clinical researcher, and statistician. Possible alternatives to unresolved issues are discussed.

There were 17 experts from academia, the pharmaceutical industry, and the US Food and Drug Administration who met on April 19, 2007, to consider the issues. Many others from sponsoring firms observed the proceedings.

A series of papers was presented at a consensus meeting and, after discussions, a sense of the participants was obtained. A small group subsequently reviewed the material and articles from the literature and prepared this article, which was reviewed by all of the participants.

The elements that form the basis for describing onset of treatment benefit include defining a clinical event or measurable threshold that validly signals that a treatment has begun to provide clinically meaningful and sustained improvement and utilizing methods for estimating the probability of crossing the onset threshold, the distribution of time to onset for those who do cross, and when to alter or change interventions if the treatment is unsuccessful.