Determination of a clinically important difference and definition of a responder threshold for the UCSD performance-based skills assessment (UPSA) in patients with major depressive disorder

Abstract Background This article reports an evaluation of the psychometric properties and clinically important difference (CID) threshold of the UCSD Performance-Based Skills Assessment (UPSA) in major depressive disorder (MDD), using data from a large-scale study of the effects of vortioxetine on cognitive functioning and functional capacity in MDD patients. Methods Adults with moderate-to-severe recurrent MDD and self-reported cognitive dysfunction were randomized to 8 weeks of double-blind treatment with vortioxetine 10/20 mg QD (flexible), duloxetine 60 mg QD, or placebo. Pearson correlation coefficients were calculated between UPSA composite score and demographic/disease characteristics at baseline to examine construct validity. Two methods (distribution-based and anchor-based) were used to establish a CID threshold. Results A total of 602 patients were randomized; 528 comprised the full analysis set. For the entire sample mean UPSA composite scores were 77.8 at baseline and 83.9 at week 8 (mean change, +6.1). As hypothesized, at baseline, the UPSA composite score correlated with cognitive functioning (Digit Symbol Substitution Test: r =0.36, P