SUBJECT SELECTION BIASES IN CLINICAL-TRIALS - DATA FROM A MULTICENTERSCHIZOPHRENIA TREATMENT STUDY

To evaluate subject selection biases in clinical trials, demographic c haracteristics (gender, race, and age) of subjects at different phases of evaluation for a multicenter maintenance trial in schizophrenia we re examined. Six thousand twelve diagnostically appropriate subjects w ere screened for the study; of these, 1,320 met eligibility criteria a nd 528 (9% of the screened sample) entered the study, Women, blacks, a nd older subjects were more likely not to meet eligibility criteria; w omen and older subjects were more Likely and blacks were less Likely t o refuse study participation. Overall, compared with the screened popu lation, the sample of subjects who entered the study contained proport ionately fewer women (33 vs. 43%), more blacks (48.5 vs. 41%), and few er 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 t hese selection factors, a second goal was to assess the potential clin ical relevance of selection biases of these magnitudes on clinical tri als using models of hypothetical studies with different degrees of sel ection bias. These showed that selection biases would rarely change ov erall study outcomes to a clinically relevant degree. However, in our models, selection biases did Limit the ability to make inferences abou t results for select small subgroups of the study population. Investig ators should consider collecting data on the recruitment process to al low estimation of the effects of selection biases on the generalizabil ity of their findings.