Beyond study participants: a framework for engaging patients in the selection or development of clinical outcome assessments for evaluating the benefits of treatment in medical product development.

BACKGROUND: Patients are participating more actively in health care decision-making with regard to their health, as well as in the broader realm of assessing the value of medical products and influencing decisions about their registration and reimbursement. There is an increasing trend to include patients' perspectives throughout the stages of medical product development by broadening the traditional study-participant role to that of an active partner throughout the process. Including patients in the selection and development of clinical outcome assessments (COAs) to evaluate the benefit of treatment is particularly important. Still, despite widespread enthusiasm, there is substantial uncertainty regarding how and when to engage patients in this process. PURPOSE: This manuscript proposes a methodological framework for engaging patients at varying levels in the selection and development of COAs for medical product development. FRAMEWORK: The framework builds on the Food and Drug Administration's roadmap for patient-focused COA. Methods for engaging patients across each stage in this roadmap are summarized by levels of engagement. Opportunities and examples of patient engagement (PE) in the selection and/or development of COAs are summarized, together with best practices and practical considerations. CONCLUSION: This paper offers a framework for understanding, planning, and implementing methods to advance PE in the selection and/or development of COAs for evaluating the benefit of medical products. The intent is to further this important discussion and enhance the process and outcome of PE in this context.

Effects on health-related quality of life in patients treated with lurasidone for bipolar depression: results from two placebo controlled bipolar depression trials.

BACKGROUND: Depressive symptoms associated with bipolar disorder negatively impact health-related quality of life (HRQoL). The efficacy of lurasidone in reducing depressive symptoms has been previously demonstrated. The objective of this study was to examine the direct and indirect effect (mediated through improvement in depression symptoms) of lurasidone in improving patient HRQoL. METHODS: A secondary analysis of data was conducted of two 6-week, double-blind, placebo-controlled trials assessing the effect of lurasidone (lurasidone monotherapy [20-60 mg/day or 80-120 mg/day]; lurasidone adjunctive to lithium or valproate [20-120 mg/day]) in patients with bipolar depression. Patient HRQoL was measured using the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q SF). Depression symptoms were measured using the Montgomery-Asberg Depression Rating Scale (MADRS). Analysis of covariance (ANCOVA) was used to estimate the effect of lurasidone on improvement in the Q-LES-Q SF percentage maximum score from baseline to 6 weeks. Path analysis was used to evaluate the total effect (ß1), as well as the indirect (ß2*ß3) and direct (ß4) effect of lurasidone on Q-LES-Q SF change through improvements in MADRS. RESULTS: A total of 340 and 485 patients from the monotherapy and adjunctive therapy, respectively, were included in the analysis. At 6-weeks, ANCOVA analyses demonstrated that lurasidone provided significant improvement in adjusted mean Q-LES-Q SF scores in comparison to placebo for monotherapy (22.9 and 22.7 vs. 15.2, both p < 0.01) and adjunctive therapy (23.1 vs. 17.9, p = 0.01). Path analyses indicated that lurasidone treatment predicted MADRS improvement (monotherapy: ß2 = -0.44, p < 0.001; adjunctive therapy: ß2 = -0.34, p = 0.003), which subsequently predicted improvement in Q-LES-Q SF (monotherapy: ß3 = -0.73, p < 0.001; adjunctive therapy: ß3 = -0.75, p < 0.001); however, the effect of lurasidone on improvement in Q-LES-Q SF was largely mediated by change in MADRS (monotherapy: ß4 = 0.11, p = 0.13; adjunctive therapy: ß4 = 0.02, p = 0.77). CONCLUSIONS: Lurasidone as a monotherapy and adjunctive to lithium or valproate is an effective treatment for improving HRQoL in patients with bipolar depression. However, improvement in HRQoL was not independent of improvement in depression, indicating that the effect of lurasidone on improving patient HRQoL may act through a reduction in depressive symptoms associated with bipolar disorder. TRIAL REGISTRATION: Clinicaltrials.gov identifiers: NCT00868699 and NCT00868452 (both registered March 23, 2009).

Effect of lurasidone on meaningful change in health-related quality of life in patients with bipolar depression.

Estimate the proportion of lurasidone-treated patients with bipolar depression who achieved a clinically meaningful improvement in health-related quality of life (HRQoL) as measured by the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q SF). A post-hoc analysis of data from two 6-week, randomized, placebo-controlled clinical trials of lurasidone as monotherapy (20-60 or 80-120 mg/day) or adjunctive therapy (20-120 mg/day) was carried out. The proportion of patients with clinically meaningful HRQoL improvement at 6 weeks was assessed using the following methods: an anchor-based method using a one-point improvement on the Clinical Global Impression-Severity, Bipolar Version (CGI-BP-S) scale; a distribution-based method using Q-LES-Q SF's SEM; and cumulative distribution functions. Data from 364 and 275 patients were available from the monotherapy and adjunctive therapy trials, respectively. Using anchor-based thresholds, a significantly higher proportion of lurasidone-treated patients reported a clinically meaningful improvement in HRQoL versus placebo in monotherapy (65.0% and 62.5 vs. 41.1%, both P<0.01) and adjunctive therapy (65.2 vs. 50.7%, P<0.05). Similar findings were observed using distribution-based thresholds for monotherapy (82.5% and 78.3 vs. 58.1%, both P<0.01) and adjunctive therapy (74.5 vs. 62.7%, P<0.05), and through the visual display of cumulative distribution functions. Short-term lurasidone monotherapy and adjunctive therapy is associated with a clinically meaningful improvement in HRQoL in patients with bipolar depression.