Subject Selection Biases in Clinical Trials

To evaluate subject selection biases in clinical trials, demographic characteristics (gender, race, and age) of subjects at different phases of evaluation for a multicenter maintenance trial in schizophrenia were examined. Six thousand twelve diagnostically appropriate subjects were screened for the study; of these, 1,320 met eligibility criteria and 528 (9% of the screened sample) entered the study. Women, blacks, and older subjects were more likely not to meet eligibility criteria; women and older subjects were more likely and blacks were less likely to refuse study participation. Overall, compared with the screened population, the sample of subjects who entered the study contained proportionately fewer women (33 vs. 43%), more blacks (48.5 vs. 41%), and fewer older subjects (mean age of the entered sample was 29.4 +/- 7.4 vs. 34.8 +/- 11.3 years for the screened population). Having identified these selection factors, a second goal was to assess the potential clinical relevance of selection biases of these magnitudes on clinical trials using models of hypothetical studies with different degrees of selection bias. These showed that selection biases would rarely change overall study outcomes to a clinically relevant degree. However, in our models, selection biases did limit the ability to make inferences about results for select small subgroups of the study population. Investigators should consider collecting data on the recruitment process to allow estimation of the effects of selection biases on the generalizability of their findings.