SF-36v2 and FACIT-Fatigue quality of life improvements with organ-specific SELENA-SLEDAI response and belimumab treatment in patients with systemic lupus erythematosus.

OBJECTIVE: Explore organ-specific SLE burden by assessing health-related quality of life (HRQoL) and fatigue changes associated with Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) organ system response (score improvement) and belimumab treatment. METHODS: Data from four phase III belimumab trials were pooled for post hoc analysis (GSK Study 217382): BLISS-52 (NCT00424476), BLISS-76 (NCT00410384), BLISS-SC (NCT01484496) and EMBRACE (NCT01632241). Patients with baseline organ system involvement were classed as organ system responders if SELENA-SLEDAI scores for that organ system decreased at any post-baseline visit. HRQoL (36-Item Short Form Health Survey version 2 (SF-36v2)) and fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)) changes over 52 weeks were compared between organ system responders and non-responders, and separately between belimumab versus placebo treatment arms among organ system responders. Group-level differences were compared using analysis of variance; differences were interpreted using published group-level minimal important difference (MID). RESULTS: In these post hoc analyses, musculoskeletal and mucocutaneous organ system responders had greater SF-36v2 improvements than non-responders across most SF-36v2 domains, but differences were largely MID), with FACIT-Fatigue also improving >MID for renal responders receiving belimumab. CONCLUSIONS: SLE disease burden differs with the organ system(s) involved. While these analyses are limited by mutual inclusivity of organ system groupings, differing patient numbers between groups and small numbers in some groups, they suggest that mucocutaneous and musculoskeletal organ system response improves SF-36v2 domain scores; cardiovascular and respiratory organ system response may meaningfully improve fatigue; and belimumab may offer additional HRQoL or fatigue benefits beyond standard therapy for musculoskeletal and renal responders.

Meaningful score changes for SF-36v2, FACIT-fatigue, and RASIQ in rheumatoid arthritis.

BACKGROUND: Interpretation thresholds for patient-reported outcome (PRO) scores are of crucial importance, particularly when interpreting treatment benefit. This study was designed to determine the within-patient meaningful improvement (WPMI) thresholds for the Short-Form 36 Health Survey version 2 (SF-36v2), the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), and the novel Rheumatoid Arthritis Symptoms and Impact Questionnaire (RASIQ) among patients with rheumatoid arthritis (RA). METHODS: In this post-hoc analysis, anchor-based and supportive distribution-based methods were used to derive WPMI based on blinded data from all treatment arms in two Phase 2 RA trials with otilimab. Patient's Global Assessment of Disease Activity (PtGA) was the general anchor for all SF-36v2 scales. SF-36 Patient's Global Impression of Status (PGIS), PtGA, and VT03 (an SF-36v2 item) were used as anchors for FACIT-Fatigue. SF-36 PGIS, PtGA, and Patient's Assessment of Arthritis Pain (PAIN) were anchors for RASIQ. Mean change was calculated for the anchor category associated with minimal meaningful improvement from baseline to Week 24 for SF-36v2 and FACIT-Fatigue, and to Week 12 for RASIQ. Sensitivity and specificity were used to evaluate the accuracy of estimated WPMI values. RESULTS: For the SF-36v2 physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health domains, anchor-based estimates of WPMI based on 0-100 scores were 24.5, 24.5, 25.4, 13.6, 21.5, 20.5, 16.9, and 14.3, respectively. Anchor-based WPMI estimates were 9.7 for the Physical Component Summary score and 7.6 for the Mental Component Summary score (using norm-based T-score metric). For FACIT-Fatigue (range 0-52), WPMI estimates ranged from 9.7 to 11.3 points. For RASIQ (range 0-100), anchor-based WPMI was determined as a change between -32.7 and -21.7 points for the Joint Pain scale, -26.7 to -23.7 for the Joint Stiffness scale, and -21.1 to -17.4 for the Impact scale. CONCLUSIONS: This study derived WPMI thresholds for SF-36v2, FACIT-Fatigue, and RASIQ among patients with RA, using multiple anchors. Derivation of WPMI thresholds for these PRO instruments will enable their broader use in evaluating and interpreting treatment benefit in future RA studies.

When assessing medical treatments in clinical trials, it is important to understand whether the treatment improves symptoms or impacts of a disease to an extent which is meaningful for patients. Patients are often asked to complete questionnaires about their symptoms throughout clinical trials to measure if and how symptoms change. Questionnaire responses are used to calculate a score that is compared before and after treatment. This study was designed to investigate how much scores in three questionnaires (SF-36v2, FACIT-Fatigue, and RASIQ) changed for patients with rheumatoid arthritis who reported experiencing meaningful symptom improvement based on data from two clinical trials. As the RASIQ is a new questionnaire that was designed specifically for rheumatoid arthritis, this research is particularly important for interpretation of RASIQ results.

Linking changes in quality of life to haematologic response and survival in systemic immunoglobulin light-chain amyloidosis.

This study reports health-related quality of life (HRQL) among newly-diagnosed immunoglobulin light-chain (AL) patients (n = 914) treated with a bortezomib-based regimen and its association with response depth and survival. Haematologic response/HRQL were assessed over 24 months in an ongoing, prospective study. HRQL change was calculated across haematologic/cardiac response levels. The relationship between baseline HRQL and survival was evaluated by the Cox proportional-hazard model (PH). Shared-random-effects models (SREMs) estimated time-to-death conditional on current HRQL/longitudinal HRQL trajectory. At 3 months, there was consistent decline in 5/8 HRQL domains across all haematologic response levels. By 12 months, 3/5 declining domains improved among complete response (CR) patients. In contrast, the mean change in less-than-CR patients did not indicate improvement. Under the Cox PH, having a baseline HRQL score five points higher than the sample mean was associated with 20% lower mortality risk. SREMs indicated a five-point greater HRQL score at the event time correlated with an approximately 30% decrease in mortality risk. For each one-point increase in HRQL score trajectory slope, mortality risk decreased by approximately 88%. Only CR patients had HRQL improvement, while partial response patients had less decline but no meaningful improvements. These data show the importance of HRQL serial assessments of AL patients and its importance as an end-point.

Development, psychometric evaluation and cognitive debriefing of the rheumatoid arthritis symptom and impact questionnaire (RASIQ).

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease often associated with persistent pain. There is a need for a patient-reported outcome measure (PROM) that is rooted in the patient experience and psychometrically validated. We describe the development of the Rheumatoid Arthritis Symptom and Impact Questionnaire (RASIQ), a novel PROM with potential to record key symptoms and impacts of RA with a 24-h recall period. RESULTS: A literature review identified RA concepts that patients considered most important to their disease experience, including pain, fatigue, joint swelling and stiffness. From this, an initial item pool (33 items; 27 related to symptoms, 6 related to impacts) was developed with a recall period of 24 h. Two rheumatologists evaluated each item's relevance, and the second version of the RASIQ was refined (29 items; 21 related to symptoms, 8 related to impacts). Next, three rounds of cognitive debriefing interviews were conducted with patients with RA (n = 15 overall). The RASIQ was revised to remove items deemed irrelevant or redundant, leaving 16 items measuring symptoms (joint pain, energy/tiredness, joint stiffness) and impacts (rest, sleep). A parallel series of semi-structured concept elicitation interviews (n = 30) facilitated the design of a conceptual model of RA symptoms, impacts and treatment experiences. Post-hoc comparison of the model with RASIQ revealed that all items selected were among the most important and relevant symptoms and impacts for patients. A final round of cognitive debriefing interviews (n = 12) confirmed that the final 16-item RASIQ was relevant and easy to understand, with no further changes recommended. Psychometric evaluation using data from two Phase II RA clinical trials confirmed a 3-factor structure, as well as the reliability and validity of the scale scores, and the ability of RASIQ to detect changes in symptoms and impacts when administered at specific study timepoints, using a 24-h recall period. CONCLUSIONS: RASIQ is a novel, 16-item PROM developed with substantial patient input. Results from concept elicitation, cognitive debriefing, and psychometric evaluation confirmed the validity of the instrument, which has the potential to measure symptoms and impacts through a 24-h recall period and complement existing disease activity instruments with longer recall periods.

Core outcome set for preventive intervention trials in chronic and episodic migraine (COSMIG): an international, consensus-derived and multistakeholder initiative.

OBJECTIVE: Typically, migraine prevention trials focus on reducing migraine days. This narrow focus may not capture all that is important to people with migraine. Inconsistency in outcome selection across trials limits the potential for data pooling and evidence synthesis. In response, we describe the development of core outcome set for migraine (COSMIG). DESIGN: A two-stage approach sought to achieve international, multistakeholder consensus on both the core domain set and core measurement set. Following construction of a comprehensive list of outcomes, expert panellists (patients, healthcare professionals and researchers) completed a three-round electronic-Delphi study to support a reduction and prioritisation of core domains and outcomes. Participants in a consensus meeting finalised the core domains and methods of assessment. All stages were overseen by an international core team, including patient research partners. RESULTS: There was a good representation of patients (episodic migraine (n=34) and chronic migraine (n=42)) and healthcare professionals (n=33) with high response and retention rates. The initial list of domains and outcomes was reduced from >50 to 7 core domains for consideration in the consensus meeting, during which a 2-domain core outcome set was agreed. CONCLUSION: International and multistakeholder consensus emerged to describe a two-domain core outcome set for reporting research on preventive interventions for chronic and episodic migraine: migraine-specific pain and migraine-specific quality of life. Intensity of migraine pain assessed with an 11-point Numerical Rating Scale and the frequency as the number of headache/migraine days over a specified time period. Migraine-specific quality of life assessed using the Migraine Functional Impact Questionnaire.

Psychometric properties of FACIT-Fatigue in systemic lupus erythematosus: a pooled analysis of three phase 3 randomised, double-blind, parallel-group controlled studies (BLISS-SC, BLISS-52, BLISS-76).

BACKGROUND: Fatigue is a key symptom in patients with systemic lupus erythematosus (SLE), and regulatory bodies recommend its assessment in clinical trials of SLE therapies. METHODS: This post hoc pooled analysis of the three BeLimumab In Subjects with Systemic lupus erythematosus (BLISS) Phase 3 randomised, double-blind, parallel-group controlled trials evaluated the measurement properties of the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue. Patients (N = 2520) completed the FACIT-Fatigue every 4 weeks from baseline until the end of each study period. Internal consistency, test-retest reliability, convergent validity, and ability to detect changes in SLE were evaluated for the FACIT-Fatigue. RESULTS: The FACIT-Fatigue showed good internal consistency reliability (Cronbach's alpha > 0.90), very good test-retest reliability (0.76 ≤ intraclass correlation coefficient ≤ 0.92), and moderate-strong convergent validity (0.49 ≤ |r| ≤ 0.86) against scale and summary measure scores from the Short Form 36 Health Survey Version 2. Correlations between FACIT-Fatigue and British Isles Lupus Assessment Group (BILAG) General/Musculoskeletal scores (0.24 ≤ |r| ≤ 0.43) supported convergent validity. Correlations between FACIT-Fatigue and the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) scores and SLE annualised flare rate were weak but in the expected direction (ranging from - 0.02 to - 0.25). Known-groups validity testing showed that the FACIT-Fatigue can significantly discriminate between patient groups with differing scores for SELENA-SLEDAI, BILAG (General and Musculoskeletal) ratings, and Physician's Global Assessment (PGA). Patients showing improvement in PGA and meeting the BILAG responder criteria had significantly higher mean improvement in FACIT-Fatigue scores than those without improvements in either measure (Week 52 mean score difference [95% confidence interval]: - 4.0 [- 5.0, - 3.0] and -2.2 [-3.1, -1.2], respectively; both p < 0.0001). The range of important (i.e. meaningful) change in FACIT-Fatigue, based on multiple anchors, was 3-6 points. CONCLUSIONS: The FACIT-Fatigue demonstrated adequate psychometric properties in patients with SLE. The body of evidence from the three BLISS trials (both pooled and individually) supports the FACIT-Fatigue as a reliable and valid measure of SLE-related fatigue in clinical trials. CLINICAL TRIAL IDENTIFIERS: BLISS-SC (NCT01484496), BLISS-52 (NCT00424476), and BLISS-76 (NCT00410384).

Health-related quality of life predicted subsequent health care resource utilization in patients with active cancer.

PURPOSE: The objective of this study was to estimate the association between SF-12v2® Health Survey (SF-12v2) scores and subsequent health care resource utilization (HCRU) among patients with cancer. METHODS: We analyzed 18+ year participants in the Medical Expenditure Panel Survey, diagnosed with active cancer or malignancy (n = 647). HCRU was measured by total medical expenditures (MEs) and number of medical events (EVs) in the 6 months following the SF-12v2 assessment. The effect of SF-12v2 scores (physical (PCS) and mental (MCS) component summary scores and the SF-6D health-utility score) on HCRU was estimated using generalized linear models. Estimates were obtained for the entire sample and for the four cancer groups present in the sample: breast, prostate, skin, and lung. RESULTS: For PCS and MCS, a one-point better score was associated with 2% lower MEs (P < 0.001) and 2.5% lower MEs (P = 0.015), respectively. A 0.05-point better SF-6D score was associated with 7% lower MEs (P = 0.003). PCS and SF-6D were more strongly associated with MEs for prostate cancer patients (P = 0.009 and P = 0.003) and PCS was more strongly associated with MEs for skin cancer patients (P = 0.019), compared to other cancer groups. A 1-point better PCS predicted 1% lower EVs, while a 0.05 better SF-6D score predicted 4% lower EVs. CONCLUSIONS: The significant associations between SF-12v2 scores from oncology patients and subsequent HCRU can guide interpretations of SF-12v2 scores in evaluation of therapies and in health policy decisions.

Estimated medical expenditure and risk of job loss among rheumatoid arthritis patients undergoing tofacitinib treatment: post hoc analyses of two randomized clinical trials.

Objectives: RA causes high disability levels and reduces health-related quality of life, triggering increased costs and risk of unemployment. Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. These post hoc analyses of phase 3 data aimed to assess monthly medical expenditure (MME) and risk of job loss for tofacitinib treatment vs placebo. Methods: Data analysed were from two randomized phase 3 studies of RA patients (n = 1115) with inadequate response to MTX or TNF inhibitors (TNFi) receiving tofacitinib 5 or 10 mg twice daily, adalimumab (one study only) or placebo, in combination with MTX. Short Form 36 version 2 Health Survey physical and mental component summary scores were translated into predicted MME via an algorithm and concurrent inability to work and job loss risks at 6, 12 and 24 months, using Medical Outcomes Study data. Results: MME reduction by month 3 was $100 greater for tofacitinib- than placebo-treated TNFi inadequate responders (P < 0.001); >20 and 6% reductions from baseline, respectively. By month 3 of tofacitinib treatment, the odds of inability to work decreased ⩾16%, and risk of future job loss decreased ∼20% (P < 0.001 vs placebo). MME reduction by month 3 was $70 greater for tofacitinib- than placebo-treated MTX inadequate responders (P < 0.001); ⩾23 and 13% reductions from baseline, respectively. By month 3 of tofacitinib treatment, the odds of inability to work decreased ⩾31% and risk of future job loss decreased ⩾25% (P < 0.001 vs placebo). Conclusion: Tofacitinib treatment had a positive impact on estimated medical expenditure and risk of job loss for RA patients with inadequate response to MTX or TNFi.

Sarilumab plus methotrexate improves patient-reported outcomes in patients with active rheumatoid arthritis and inadequate responses to methotrexate: results of a phase III trial.

BACKGROUND: Sarilumab is a human monoclonal antibody directed against the alpha subunit of the interleukin-6 receptor complex. In the MOBILITY phase III randomized controlled trial (RCT), sarilumab + methotrexate (MTX) treatment resulted in clinical improvements at 24 weeks that were maintained at 52 weeks in adults with rheumatoid arthritis (RA), who have inadequate response to MTX (MTX-IR). These analyses indicate the effects of sarilumab + MTX versus placebo on patient-reported outcomes (PROs) in this RCT. METHODS: Patients (n = 1197) were randomized to receive placebo, sarilumab 150 or 200 mg subcutaneously + MTX every 2 weeks for 52 weeks; after 16 weeks, patients without ≥20 % improvement from baseline in swollen or tender joint counts on two consecutive assessments were offered open-label treatment. PROs included patient global assessment of disease activity (PtGA), pain, health assessment questionnaire disability index (HAQ-DI), Short Form-36 Health Survey (SF-36), and functional assessment of chronic illness therapy-fatigue (FACIT-F). Changes from baseline at weeks 24 and 52 were analyzed using a mixed model for repeated measures. Post hoc analyses included percentages of patients reporting improvements equal to or greater than minimal clinically important differences (MCID) and normative values in the FACIT-F and SF-36. Pearson correlation between observed PRO scores and clinical measures of disease activity was tested at week 24. RESULTS: Both doses of sarilumab + MTX vs placebo + MTX resulted in improvement from baseline by week 24 in PtGA, pain, HAQ-DI, SF-36 and FACIT-F scores (p < 0.0001) that was clinically meaningful, and persisted until week 52. In post hoc analyses, the percentages of patients with improvement equal to or greater than the MCID across all PROs were greater with sarilumab than placebo (p < 0.05), with differences ranging from 11.6 to 26.2 %, as were those reporting equal to or greater than normative scores. CONCLUSIONS: In this RCT in patients with MTX-IR RA, sarilumab + MTX resulted in sustained improvement in PROs that were clinically meaningful, greater than placebo + MTX, and complement the previously reported clinical efficacy and safety of sarilumab. TRIAL REGISTRATION: ClinicalTrials.gov. NCT01061736 . February 2, 2010.

Medical expenditures in patients with high risk of diabetes: Effects of BMI, hypertension, and health-related quality of life.

OBJECTIVE: To evaluate the health-related quality of life (HRQOL) of patients with diabetes and persons at high risk of developing diabetes and the association between HRQOL scores and subsequent medical expenditures in these persons. METHODS: Data came from the Medical Expenditure Panel Survey. Body mass index (BMI) and hypertension were used to identify risk of diabetes. Burden was assessed by comparing SF-12 physical (PCS) and mental (MCS) summary scores in patients with diabetes and those at risk of having diabetes to the age- and gender-adjusted PCS and MCS of those with normal BMI and no hypertension. Associations between PCS and MCS and medical expenditures were modeled using a two-part model that controlled for clinical and demographic factors. Percent increase in expenditure associated with PCS and MCS differences was evaluated as the ratio of estimated expenditure, holding other factors fixed. RESULTS: Diabetes risk factors were associated with up to 9-point lower PCS and 3-point lower MCS score. Overall, 1-, 2-, 5-, and 10-point lower PCS scores were associated with 2.9%, 5.8%, 15.0%, and 31.8% higher expenditures, and lower MCS scores were associated with 1.3%, 2.6%, 6.5%, and 13.5% higher expenditures, respectively. CONCLUSIONS: The reported associations can help clinicians and researchers interpret the magnitude of HRQOL score differences.

Health-related quality of life in thrombocytopenic patients with chronic hepatitis C with or without cirrhosis in the ENABLE-1 and ENABLE-2 studies.

BACKGROUND: Despite changes in the treatment paradigm towards non-interferon-based therapies, interferon-based treatments are still used in some geographical regions for treating patients with hepatitis C virus (HCV) infection. Use of eltrombopag with interferon-based treatment for patients with thrombocytopenia and HCV was assessed in two similarly designed phase 3 trials (Eltrombopag to Initiate and Maintain Interferon Antiviral Treatment to Benefit Subjects With Hepatitis C-Related Liver Disease [ENABLE-1 and ENABLE-2]). These trials also aimed to determine whether response to antiviral therapy (e.g., sustained virologic response [SVR]) is associated with changes in health-related quality of life (HRQoL). This pooled, post-hoc analysis aimed to (1) determine whether or not specific aspects of clinical response to treatment (i.e., achieving SVR) are associated with a significant change in HRQoL, and (2) to determine the magnitude and direction of the association between important changes in HRQoL, clinical response to interferon-based therapy (e.g., SVR) and treatment (eltrombopag or placebo), and patient and disease attributes. METHODS: The Short-Form 36 Health Survey version 2 and Chronic Liver Disease Questionnaire-Hepatitis C Virus version were administered at various time points during the studies. Results from both trials were pooled for the analyses. Logistic regression analysis was used to assess the influence of 5 clinical factors (SVR, early virologic response [EVR], genotype [2/3 vs. non-2/3], treatment [eltrombopag or placebo], and cumulative interferon dose), plus other factors including ethnicity, model of end-stage liver disease score, and platelets as predictors of meaningful changes in HRQoL. RESULTS: Between antiviral therapy baseline and the end of the 24-week post-treatment follow-up, declines in HRQoL were smaller in eltrombopag-treated patients than in placebo-treated patients, but the differences were not statistically significant. Mean changes among patients achieving SVR and EVR were small in comparison to thresholds of minimally important changes. Logistic models did not confirm the strength of the 5 clinical factors as predictors of meaningful changes in HRQoL during antiviral therapy, with the exception of the interaction between SVR and EVR (P = 0.0009). Asian ethnicity had a consistent effect on HRQoL, with East Asian patients being more likely to experience deterioration in HRQoL compared with white and/or other non-East Asian patients. CONCLUSIONS: While on active antiviral therapy, declines in HRQoL were not statistically different for eltrombopag-treated patients versus placebo-treated patients, suggesting that eltrombopag neither worsened HRQoL nor mitigated the effects of antiviral therapy on HRQoL.

Effect of ivacaftor treatment in patients with cystic fibrosis and the G551D-CFTR mutation: patient-reported outcomes in the STRIVE randomized, controlled trial.

BACKGROUND: Cystic fibrosis (CF) is an inherited, rare autosomal recessive disease that results in chronically debilitating morbidities and high premature mortality. We evaluated how ivacaftor treatment affected CF symptoms, functioning, and well-being, as measured by the Cystic Fibrosis Questionnaire-Revised (CFQ-R), a widely-used patient-reported outcome (PRO) measure. METHODS: STRIVE, a double-blind, placebo-controlled randomized trial, evaluated ivacaftor (150 mg) in CF patients aged 12+ with the G551D-CFTR mutation for 48 weeks. Treatment effect analysis used a mixed-effects repeated measures model. Treatment benefit analyses applied the cumulative distribution function and a categorical analysis of change scores ("improvement," "no change," or "decline"). Content-based interpretation examined treatment effect on specific item responses. RESULTS: Data from 152 patients with a baseline CFQ-R assessment were analyzed. The treatment effect analysis favored treatment with ivacaftor over placebo on the Body Image, Eating, Health Perceptions, Physical Functioning, Respiratory, Social Functioning, Treatment Burden, and Vitality scales. Findings were supported by the analysis of categorical change. On all CFQ-R scales, the percentage of patients who improved was greater for ivacaftor. In the content-based analysis, the treatment benefit was characterized by better scores across a broad range of domains. CONCLUSIONS: Results illustrate broad benefits of ivacaftor treatment across many domains: respiratory symptoms, physical and social functioning, health perceptions, and vitality, as measured by the CFQ-R. The breadth of improvements reflects the systemic mechanism of action of ivacaftor compared to other therapies. Findings support the patient-reported value of ivacaftor treatment in this patient population. TRIAL REGISTRATION: ClinicalTrials.gov NCT00909532.

Validation of the Headache Impact Test (HIT-6) in patients with chronic migraine.

BACKGROUND: The Headache Impact Test (HIT)-6 was developed and has been validated in patients with various types of headache. The objective of this study was to report the psychometric properties of the HIT-6 among patients with chronic migraine. METHODS: Data came from two international, multicenter, randomized, double-blind, placebo-controlled clinical trials of chronic migraine patients (N = 1,384) undergoing prophylaxis therapy. Confirmatory factor analysis and differential item functioning (DIF) analysis were used to test the latent structure and cross-cultural comparability of the HIT-6. Reliability, construct validity, and responsiveness were assessed. Two sets of criterion groups were used: (1) 28-day headache frequency: <10, 10-14, and ≥15 days; (2) sample quartiles of the total cumulative hours of headache: <140, 140 to <280, 280 to <420, and ≥420 hours. Two sets of responsiveness categories were defined as reduction of <30%, 30% to <50%, or ≥50% in (1) number of headache days and (2) cumulative hours of headache. RESULTS: Measurement invariance tests supported the stability of the HIT-6 latent structure across studies. DIF analysis supported cross-cultural comparability. Good reliability was observed across studies (Cronbach's α: 0.75-0.92; intraclass correlation coefficient: 0.76-0.80). HIT-6 scores correlated strongly (-0.86 to -0.59) with scores of the Migraine-Specific Quality-of-Life Questionnaire. Analysis of variance indicated that HIT-6 scores discriminated across both types of criterion groups (P<0.001), across studies and time points. HIT-6 change scores were significantly higher in magnitude in groups experiencing greater improvement (P<0.001). CONCLUSION: All measurement properties were consistently verified across the two studies, supporting the validity of the HIT-6 among chronic migraine patients. TRIAL REGISTRATION: NCT00156910 and NCT00168428 on www.ClinicalTrials.gov.

Measuring the effect of therapy in rheumatoid arthritis clinical trials from the patient's perspective.

OBJECTIVE: Health measurements used to evaluate the effectiveness of rheumatoid arthritis (RA) therapies often fail to reflect patients' priorities, despite recommendations towards more patient-centered assessments. The goals of the current review are: (1) to present guidelines, tools, and required steps for successful implementation of patient-reported outcome (PRO) measurement in RA clinical trials; and (2) to identify gaps between recommendations and current practices. METHODS: The first objective was addressed by reviewing existing frameworks for assessment of health-related quality of life among patients with RA and guidelines on the evaluation of PRO instruments, with a focus on evidence required to demonstrate the adequacy of PRO-based labeling claims. The second goal was addressed by conducting an empirical investigation of the overlap between patients' perspectives and current practices regarding PROs in RA studies, elaborated from systematic literature searches. The first search identified qualitative studies that reported direct input from patients with RA, while the second identified the main health outcomes measured in RA trials, with a focus on biologic therapy. RESULTS: Our review revealed a set of outcomes that have thus far not been widely used to assess treatment benefit in RA, despite evidence of their importance to patients. The psychometric properties of PRO instruments used to evaluate commonly assessed domains are presented, as are recommendations for PRO tools that assess domains less often measured in RA studies. CONCLUSIONS: Although the validity of some PRO tools among patients with RA is well established, further work needs to be done in several health domains which have traditionally received insufficient attention.

The psychometric properties of the Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ) in chronic migraine patients.

OBJECTIVE: The Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ) has been shown to have good psychometric performance in measuring headache impact in migraine patients, but its properties specifically in chronic migraine (CM) patients are unknown. The objective of this study was to evaluate the psychometric properties of the MSQ in a group of CM patients undergoing prophylactic treatment. METHODS: Measurement properties of the MSQ were examined using two international, multicenter, randomized clinical trials evaluating onabotulinumtoxinA as headache prophylaxis in CM patients (N = 1,376). Confirmatory factor analysis (CFA) was used to test the latent structure of the MSQ in CM patients. The reliability, convergent and discriminant validity, and responsiveness of the MSQ were assessed. RESULTS: CFA confirmed the currently proposed three-factor MSQ latent structure across the two studies. Good reliability was observed for all three MSQ scales, across studies and time points. MSQ scale scores strongly correlated with the scores of the Headache Impact Test-6 (HIT-6). Analysis of known-groups validity indicated that MSQ scale scores discriminated between groups of patients differing in their 28-day headache frequency were as follows <10, 10-14, and ≥ 15 days, and the sample-derived quartiles of the total cumulative hours of headache were as follows <140, 140 to <280, 280 to <420, and ≥ 420 h (p < 0.0001), across both studies and time points. MSQ change scores were higher in magnitude in groups experiencing greater decline in headache frequency (p < 0.001). CONCLUSION: The MSQ is a psychometrically valid tool that can be used to reliably measure the impact of migraine among CM patients.

Health-related quality of life (HRQL) for individuals with self-reported chronic physical and/or mental health conditions: panel survey of an adult sample in the United States.

BACKGROUND: In the US, approximately 53% of adults have at least one chronic condition. Comorbid physical and mental health conditions often have an incremental negative impact on health-related quality of life (HRQL). Primary study objectives were to quantify the impact on HRQL of a) ≥ 1 physical condition , b) ≥ 1 comorbid mental health conditions added to a physical one, c) ≥ 1 mental health condition, and d) ≥ 1 comorbid physical conditions added to at least one related to mental health. Decrements were based on a "Healthy" reference group reporting no chronic conditions. METHODS: Participants were sampled (n = 3877) from the US adult population as part of a 2009 normative survey. Demographics, number/ type of chronic conditions, and HRQL data were self-reported. HRQL was defined through SF-36v2® Physical Component Summary (PCS) scores and Mental Component Summary (MCS) scores. Participant "morbidity" groupings included Healthy; Physical Health Condition only, Mental Health Condition only, and Physical and Mental Health (Comorbid). PCS and MCS scores were also analyzed by physical disease clusters (e.g., cardiovascular, gastrointestinal). Multivariate regression models were used for all analyses. RESULTS: 81% of participants were Caucasian; 9% African American. Males and females were about equally represented; 63% were ≥ 45 years old. The average number of reported chronic conditions was 2.4 (SD = 2.4). Relative to the Healthy group, the Physical Condition group scored 6.4 (males) and 7.5 (females) points lower on PCS. The addition of a comorbid mental health condition resulted in a total reduction of 11 points in PCS and 15 points in MCS. Compared to the Healthy group, ≥ 1 mental health conditions was associated with MCS decrements of 11-12 points. A physical comorbidity led to additional decrements of 3-4 points for MCS, with a total of 15 points. Incremental HRQL burden defined by both MCS and PCS scores was relatively similar across the 5 defined physical disease clusters. CONCLUSION: Results provide quantitative information for US adults on specific PCS and MCS score decrements associated with a comorbid condition related to mental health, as well as a comorbid condition related to physical health.

Validating Migraine-Specific Quality of Life Questionnaire v2.1 in episodic and chronic migraine.

OBJECTIVE: To provide evidence for the reliability and validity of the Migraine-Specific Quality of Life Questionnaire Version 2.1 (MSQ) for use in chronic migraine (CM) in adults. BACKGROUND: MSQ is one of the most frequently utilized disease-specific tools assessing impact of migraine on health-related quality of life (HRQL). However, evidence for its reliability and validity are based on studies in episodic migraine (EM) populations. Additional studies assessing the reliability and validity of the MSQ in patients with CM are needed. METHODS: Cross-sectional data were collected via web-based survey in 9 countries/regions. Participants were classified as having CM (≥15 headache days/month) or EM (<15 headache days/month). Three MSQ domains - Role Function-Preventive (RP), Role Function-Restrictive (RR), and Emotional Function (EF) - were rescaled to 0-100, where higher scores indicate better HRQL, and analyzed for internal consistency reliability (Cronbach's α), construct validity (correlations between MSQ scales and measures of depression/anxiety [Patient Health Questionnaire; PHQ-4], disability [Migraine Disability Assessment Questionnaire; MIDAS], and functional impact [Headache Impact Test; HIT-6], where lower scores indicate better HRQL for each measure), as well as discriminant validity across migraine groups. RESULTS: A total of 8726 eligible respondents were classified: 5.7% CM (n = 499) and 94.3% EM (n = 8227). Subjects were mostly female (83.5%) with a mean (±SD) age of 40.3 ± 11.4, and were similar between the 2 groups. MSQ domain scores for CM and EM groups, respectively, were: RP = 61.4 ± 26.1 and 71.7 ± 24.0; RR = 44.4 ± 22.1 and 56.5 ± 24.1; EF = 48.3 ± 28.1 and 67.2 ± 26.7. Internal consistency of the overall sample for RP, RR, and EF was 0.90, 0.96, and 0.87, respectively. Similar values were observed for CM and EM. MSQ scores for the overall sample correlated moderately to highly with scores from the PHQ-4 (r = -0.21 to -0.42), MIDAS (r = -0.38 to -0.39), and HIT-6 (r = -0.60 to -0.71). Similar values were observed for CM and EM. Known-groups validity indicated significant differences (P < .0001) in the hypothesized direction between CM and EM for RP (F = 86.19), RR (F = 119.24), and EF (F = 235.90). CONCLUSION: The MSQ is a reliable and valid questionnaire in the CM population that can differentiate the functional impact between CM and EM. The MSQ can assist researchers in evaluating treatment effectiveness by obtaining input directly from the patients on multidimensional aspects other than frequency of headache days.

Psychometric validation of the revised SCOPA-Diary Card: expanding the measurement of non-motor symptoms in Parkinson's disease.

BACKGROUND: To identify key non-motor symptoms of Parkinson's disease (PD) to include in a daily diary assessment for off-time, revise the Scales for Outcomes of Parkinson's disease Diary Card (SCOPA-DC) to include these non-motor symptoms, and investigate the validity, reliability and predictive utility of the Revised SCOPA-DC in a U.S. population. METHODS: A convenience sample was used to recruit four focus groups of PD patients. Based on findings from focus groups, the SCOPA-DC was revised and administered to a sample of 101 PD patients. Confirmatory factor analysis was conducted to test the domain structure of the Revised SCOPA-DC. The reliability, convergent and discriminant validity, and ability to predict off-time of the Revised SCOPA-DC were then assessed. RESULTS: Based on input from PD patients, the Revised SCOPA-DC included several format changes and the addition of non-motor symptoms. The Revised SCOPA-DC was best represented by a three-factor structure: Mobility, Physical Functioning and Psychological Functioning. Correlations between the Revised SCOPA-DC and other Health-Related Quality of Life scores were supportive of convergent validity. Known-groups validity analyses indicated that scores on the Revised SCOPA-DC were lower among patients who reported experiencing off-time when compared to those without off-time. The three subscales had satisfactory predictive utility, correctly predicting off-time slightly over two-thirds of the time. CONCLUSIONS: These findings provide evidence of content validity of the Revised SCOPA-DC and suggest that a three-factor structure is an appropriate model that provides reliable and valid scores to assess symptom severity among PD patients with symptom fluctuations in the U.S.

Evaluating the efficacy of sequential biologic therapies for rheumatoid arthritis patients with an inadequate response to tumor necrosis factor-α inhibitors.

INTRODUCTION: The long-term treatment of rheumatoid arthritis (RA) most often involves a sequence of different therapies. The response to therapy, disease progression and detailed knowledge of the role of different therapies along treatment pathways are key aspects to help physicians identify the best treatment strategy. Thus, understanding the effectiveness of different therapeutic sequences is of particular importance in the evaluation of long-term RA treatment strategies. The objective of this study was to systematically review and quantitatively evaluate the relationship between the clinical response to biologic treatments and the number of previous treatments with tumor necrosis factor α (TNF-α) inhibitors. METHODS: A systematic search was undertaken to identify published, peer-reviewed articles that reported clinical outcomes of biologic treatment among RA patients with an inadequate response to TNF-α inhibitors. Data were systematically abstracted. Efficacy rates were estimated for groups of patients who differed in the number of prior TNF-α inhibitors used. End points included American College of Rheumatology (ACR)-, European League Against Rheumatism (EULAR)- and Disease Activity Score 28 (DAS28)-based response criteria. RESULTS: The literature search identified 41 publications, of which 28 reported biologic treatment outcomes for RA patients with prior exposure to TNF-α inhibitors. Seven publications reported outcomes obtained in randomized clinical trials, while the remaining consisted of observational studies. The likelihood of responding to a subsequent biologic treatment decreased as the number of previous treatments with TNF-α inhibitors increased for six of the seven response criteria examined. CONCLUSIONS: For patients with prior exposure to TNF-α inhibitors, the likelihood of response to subsequent treatment with biologic agents declines with the increasing number of previous treatments with TNF-α inhibitors.

Psychometric evaluation of the Glaucoma Symptom Identifier.

OBJECTIVE: To evaluate the psychometric properties of the Glaucoma Symptom Identifier (GSI), a tool designed to assess multiple possible glaucoma symptoms and their impact on quality of life in clinical practice. We sought to address the need for better methods to assess visual function related to quality of life of glaucoma patients with a tool to show to both physicians and their patients that glaucoma is not an asymptomatic disease. The development process was to provide comprehensive assessment in 1 page of the impact of glaucoma on patients' quality of life by including an exhaustive list of unique and nonredundant items. DESIGN: Cross-sectional online survey. PARTICIPANTS: Seven hundred and eighteen individuals with a self-reported diagnosis of glaucoma, who were at least 40 years of age. METHODS: The impact of glaucoma was assessed by asking study participants the degree of difficulty they experience on a number of tasks. Item response theory was used to psychometrically evaluate the GSI. Scores on the GSI and the SF-12, a generic quality-of-life instrument, were compared. MAIN OUTCOME MEASURES: Items in the GSI were categorized in terms of their ability to capture glaucoma impact on quality of life across the population range of subjects from mild-to-severe glaucoma severity. RESULTS: The GSI showed good reliability, and convergent and discriminant validity. Items in the GSI captured glaucoma impact on quality of life over an adequate range of disease severity. Potential improvements to the existing questionnaire were identified using item response theory modeling results and respondents' feedback on the survey. CONCLUSIONS: Our findings suggest that the GSI is a psychometrically valid tool, adequate for glaucoma patients' self-administration within a clinician's routine practice to help both the patient and physician assess the patient's current and potential future symptoms of glaucoma.