Addressing methodological issues in studying antidepressant onset efficacy using prespecified sensitivity analyses.
OBJECTIVE
Assessing antidepressant onset efficacy presents substantial methodological challenges. Most assessments of onset efficacy are based on post hoc analyses. This article presents a case study of a prospectively designed trial to compare antidepressant onset efficacy.


METHODS
The current study design was compared with previously published criteria for an ideal onset of action study. Prospectively defined sensitivity analyses were used to assess whether results of the present study were influenced by the assumptions and decisions necessary to implement this study.


RESULTS
The study achieved its primary objective of establishing noninferiority between SNRI and SSRI. Sensitivity analyses suggested that results from the primary analysis were not influenced by patient population, outcome measure, cut-off for defining clinically meaningful sustained improvement, or analytical method. Although not all limitations could be addressed, appropriate conclusions could be drawn. For example, the study tested only one fixed dose of each drug; hence, conclusions are limited to those dosages and cannot be extrapolated across the entire dose ranges, as would be possible in the ideal study.


CONCLUSIONS
This article illustrates that prospectively designed studies (as opposed to retrospective comparisons) can be implemented and sensitivity analyses can be used to address concerns regarding assumptions and arbitrary decisions.
Lipkovich
Ilya
I
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
Mallinckrodt
Craig H
CH
Prakash
Apurva
A
Nierenberg
Andrew A
AA
D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D011446:Prospective Studies; D012107:Research Design
D000928:Antidepressive Agents