Introduction
schizophrenia, treatment-responsive
REGRESSION, SEPARATION, SYNDROME, POSITIVE
The 30-item Positive and Negative Syndrome Scale (PANSS-30) is a commonly used scale that measures the severity of symptoms of schizophrenia across multiple domains [One aspect of the main PANSS subscales, as well as of the PANSS-6, that has not been thoroughly evaluated, is the extent to which they show similar features as the PANSS-30 does across the full severity spectrum commonly included in trials of patients with schizophrenia. Specifically, for PANSS-30, it has been demonstrated that initial symptom severity correlates positively with antipsychotic-placebo separation [While, due to regression to the mean, a positive association between initial symptom severity and absolute change scores might be expected for all treatment groups, the same phenomenon would not explain why such an association would be stronger in patients receiving antipsychotics than in patients receiving placebo. There are two likely explanations for why antipsychotic-placebo separation would increase with initial symptom severity. First, it might be that patients with higher initial symptom severity are more likely to experience true drug effects and/or that they are less likely to have substantial placebo effects, possibly because they are more likely genuinely/severely exacerbated patients. Second, a constant fraction of treatment-responsive patients across the severity spectrum could also yield a numerical association between initial severity and antipsychotic-placebo separation if the response in that fraction is proportional to initial severity. Analyses of the relationship between baseline symptom severity using both relative and absolute outcome measures are necessary to disentangle those possibilities from one another.In this study, we, therefore, assessed the relationship between initial symptom severity and antipsychotic-placebo separation as measured by PANSS-30, its positive (PANSS-POS), negative (PANSS-NEG), and general (PANSS-GEN) subscales, as well as by PANSS-6. In order to gain a better understanding of potential initial severity-by-treatment interactions, we assessed it using both absolute (mean group differences) and relative (fraction of participants displaying different levels of change from baseline) outcome measures. We also assessed the association between initial severity on PANSS-30 and its four subscales, and risk of trial dropout. We hypothesized that relationships between initial symptom severity on PANSS-30 and the studied outcomes [