Effectiveness Trials in Schizophrenia: Necessary. Sufficient?

Background Clinical trials are criticized for excluding important clinical populations. Effectiveness trials propose to mitigate this, but whether they succeed has not been studied. We compared exclusion criteria in efficacy and effectiveness clinical trials and assessed their impact on eligibility in a clinical sample. Methods We used Qualitative Content Analysis to extract common exclusion criteria from recent trials, then assessed their frequencies among a one-month sample of adults in an emergency department with psychosis. Results Among 107 unique clinical trials, efficacy trials utilized 12.3 exclusion criteria categories on average, while effectiveness trials utilized 9.1. Efficacy trials were more likely to have exclusions for substance use, suicide risk, violence risk, and medical problems. In the clinical sample (N = 297), substance use, suicide risk, and violence risk had the greatest impact on eligibility, excluding 85.5% of patients. Other exclusion criteria also impact eligibility; trials that allow substance use, suicide risk, and violence risk would still likely exclude 81.8%. Conclusions Effectiveness trials do utilize fewer exclusion criteria than efficacy trials, but the difference is incremental and does not resolve generalizability problems. Even a few exclusion criteria can have a large impact on eligibility. Development of an evidence base for under-studied populations is needed.