Impact of the treatment-free interval on health-related quality of life in patients with multiple myeloma: a UK cross-sectional survey.

BACKGROUND: While the impact of various treatments on myeloma patients' health-related quality of life (HRQL) has been reported, the impact of a treatment-free interval (TFI) is currently unclear. The aims of this study were to assess if (1) a TFI is associated with a better HRQL vs. other treatment phases and (2) the length of the TFI influences HRQL. METHODS: A cross-sectional postal survey was conducted in the UK. The survey was sent to 605 multiple myeloma patients via the charity Myeloma UK and asked patients to rate their HRQL using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30), EORTC QLQ-MY20 and the EQ-5D. The results were analysed using ordinary least squares regression. RESULTS: Surveys of 402 (67 %) were returned; 370 (61 %) were considered eligible for analysis. Results demonstrated that being in a first TFI relative to other treatment phases and experiencing a longer TFI were significantly associated with better HRQL as assessed by various domains of the QLQ-C30, MY20 and EQ-5D. CONCLUSION: Patients enjoy better HRQL when in their first TFI, and the length of the TFI also positively impacts on HRQL This information may be important for patients and their physicians making treatment decisions and has implications for treatment protocols incorporating extended therapy.

Methods for interpreting change over time in patient-reported outcome measures.

PURPOSE: Interpretation guidelines are needed for patient-reported outcome (PRO) measures' change scores to evaluate efficacy of an intervention and to communicate PRO results to regulators, patients, physicians, and providers. The 2009 Food and Drug Administration (FDA) Guidance for Industry Patient-Reported Outcomes (PRO) Measures: Use in Medical Product Development to Support Labeling Claims (hereafter referred to as the final FDA PRO Guidance) provides some recommendations for the interpretation of change in PRO scores as evidence of treatment efficacy. METHODS: This article reviews the evolution of the methods and the terminology used to describe and aid in the communication of meaningful PRO change score thresholds. RESULTS: Anchor- and distribution-based methods have played important roles, and the FDA has recently stressed the importance of cross-sectional patient global assessments of concept as anchor-based methods for estimation of the responder definition, which describes an individual-level treatment benefit. The final FDA PRO Guidance proposes the cumulative distribution function (CDF) of responses as a useful method to depict the effect of treatments across the study population. CONCLUSIONS: While CDFs serve an important role, they should not be a replacement for the careful investigation of a PRO's relevant responder definition using anchor-based methods and providing stakeholders with a relevant threshold for the interpretation of change over time.

Can the functional assessment of multiple sclerosis adapt to changing needs? A psychometric validation in patients with clinically isolated syndrome and early relapsing-remitting multiple sclerosis.

BACKGROUND: The Functional Assessment of Multiple Sclerosis (FAMS) is widely used in clinical trial programmes; however, it was developed before the rise in trials targeted at early stage multiple sclerosis (MS) and clinically isolated syndrome (CIS). OBJECTIVE: The aim of this study was to assess the psychometric properties of the FAMS within two clinically distinct populations, CIS and early relapsing-remitting MS (RRMS), and discern the appropriateness of the FAMS within these populations. METHODS: Secondary analysis was conducted on FAMS data from two clinical trials assessing interferon beta-1b in early RRMS and CIS. The statistical analysis assessed the scale acceptability, reliability, validity and responsiveness of the FAMS. Item response theory (IRT) was also conducted on the early RRMS sample in order to assess how well the FAMS discriminated amongst individuals with less severe MS. RESULTS: Results from both trials demonstrated an improvement in the FAMS psychometric properties with increased baseline disease severity. However, high ceiling effects were evident amongst less severe patients, and there was an overall lack of responsiveness to improvement and poor construct validity. IRT also demonstrated its lack of discrimination/sensitivity in early RRMS. CONCLUSIONS: In trials involving patients with early stage RRMS and CIS, modifications to the FAMS based on a qualitative assessment of its content validity in these populations would be required in order to potentially improve the FAMS psychometric properties and sensitivity.