This chapter explains the responsiveness and sensitivity of a patient-reported outcome (PRO) measure or, more generally, other types of clinical outcome assessments (COA). A measurement scale is futile for patient monitoring unless it can reflect changes in a patient's condition over time and be sensitive to treatment effects. In its updated and expanded guidance, the United Stated Food and Drug Administration provides insight and guidance on the ability to detect change for COA, which include PRO tools as well as clinician-reported outcome, observer reported outcome, and performance-based outcome tools. The chapter provides a framework and an implementation of applying one unified multi-domain longitudinal model, intended for a scale with multiple domains assessed over time, as a way to assess treatment effects and increase the efficiency of the analyses.
Background Pain is a core domain of psoriatic arthritis (PsA). This post hoc analysis evaluated time to pain improvement and the impact of baseline pain severity on pain response in patients with PsA receiving tofacitinib. Methods Data from two trials ( NCT01877668 ; NCT01882439 ) in patients receiving tofacitinib 5 mg twice daily, placebo switching to tofacitinib 5 mg twice daily at month 3 (placebo-to-tofacitinib) or adalimumab ( NCT01877668 only) were included. Improvement in pain (≥30%/≥50% decrease from baseline in Visual Analogue Scale pain score) was assessed; median time to initial (first post-baseline visit)/continued (first two consecutive post-baseline visits) pain improvement was estimated (Kaplan-Meier) for all treatment arms. A parametric model was used to determine the relationship between baseline pain severity and time to pain response in patients receiving tofacitinib. Results At month 3, more patients experienced pain improvements with tofacitinib/adalimumab versus placebo. Median days (95% CI) to initial/continued pain improvements of ≥30% and ≥50%, respectively, were 55 (29–57)/60 (57–85) and 85 (57–92)/171 (90–not estimable (NE)) for tofacitinib, versus 106 (64–115)/126 (113–173) and 169 (120–189)/NE (247–NE) for placebo-to-tofacitinib. Pain improvements were also experienced more quickly for adalimumab versus placebo. Predicted time to ≥30%/≥50% pain improvement was shorter in patients with higher baseline pain versus lower baseline pain (tofacitinib arm only). Conclusions In patients with PsA, pain improvements were experienced by more patients, and more rapidly, with tofacitinib and adalimumab versus placebo. In those receiving tofacitinib, higher baseline pain was associated with faster pain improvements.
Background: Cigarette smoking causes reduced health-related quality of life (QoL) and smoking abstinence improves health-related QoL. We assessed the effects of treatment for tobacco dependence on the health-related QoL in a 52-week randomized controlled trial of varenicline and bupropion sustained release (SR). Methods: Subjects who smoked ≥10 cigarettes per day for the past year were randomly assigned to receive varenicline 1 mg twice daily (n = 696), bupropion SR 150 mg twice daily (n = 671) or placebo (n = 685) for 12 weeks and followed post-therapy for an additional 40 weeks. Health-related QoL was assessed using the Smoking Cessation Quality of Life questionnaire at baseline and Weeks 12, 24 and 52. Results: Health transition (perceived health compared with baseline) and self-control were both significantly improved among subjects receiving varenicline and bupropion SR compared with placebo at Weeks 12, 24 and 52. Similarly, varenicline-treated subjects had significantly improved health transition and self-control compared with subjects who received bupropion SR at Weeks 12 and 24, and at Week 52 for health transition. A significant positive association existed between length of continuous abstinence and improved health transition, vitality, self-control, anxiety and overall mental profile. In most instances both a direct and an indirect effect (through continuous smoking abstinence) of each active treatment (vs. placebo) contributed to improved self-control and health transition. Conclusion: Treatment with varenicline and bupropion SR for smoking cessation resulted in improved self-control and health transition that was mediated in large part by continuous smoking abstinence.
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