Objective: Although emerging data indicate that sample composition may influence the effectiveness of mental health interventions, the extent to which subjects in clinical trials represent affected community samples remains unknown. The goal of this study was to assess the proportion of community-dwelling adults with major depressive episode (MDE) who would meet eligibility criteria for a traditional efficacy trial in patients with MDE.
Method: We applied a standard set of exclusion criteria used in clinical trials in patients with MDE to the 2001-2002 National Epidemiologic Survey for Alcohol and Related Conditions (NESARC), the largest psychiatric epidemiologic study in the United States to date (N = 43,093). Because individuals who seek treatment for a disorder may systematically differ from those who do not, we applied the criteria first to all individuals with a current diagnosis of MDE (N = 3119) (diagnosed according to DSM-IV) and then to the subsample of individuals who sought treatment (N = 1359).
Results: Among the full sample of individuals with MDE, 75.8% were excluded by one or more study eligibility criteria. Approximately two thirds (66.9%) of the subsample of those who sought treatment were excluded. The percentage of subjects excluded by individual study criteria ranged from 2.4% to 47.4% in the overall sample and 0% to 38.4% in the treatment-seeking sample. For both groups, the presence of comorbid, nondepressive, non-substance use Axis I disorders and the duration of the depressive episode excluded the largest percentage of individuals.
Conclusion: The design of traditional clinical trials tends to exclude a majority of individuals with MDE. Selection of exclusion criteria may have a powerful influence on the generalizability of study results. Clinical trials should explain the rationale for their exclusion criteria and estimate the impact of eligibility criteria on the generalizability of trial results.