Disease-specific patient reported outcome tools for systemic lupus erythematosus.

PURPOSE: Systemic lupus erythematosus (SLE) can significantly affect both health and non-health-related quality of life (HRQOL and non-HRQOL). However, of the existent published patient-reported outcome (PRO) tools, none were developed from US patients, an ethnically diverse population. Furthermore, these tools do not address men with SLE or assess non-HRQOL issues. Herein, we present the development and validation of the Lupus Patient-Reported Outcome tool (LupusPRO) and discuss its clinical utility and research value compared with other PRO tools currently available for SLE. METHODS: Beginning with a conceptual framework, items for LupusPRO were generated using feedback from women and men with SLE. The tool underwent iterations based on patient feedback and clinimetric and psychometric analyses. Validity (content, construct, and criterion) and reliability (internal consistency and test-retest) for the 44-item LupusPRO tool are presented. RESULTS: Consistent with the conceptual framework, items were identified that were related to HRQOL and non-HRQOL constructs. HRQOL domains included (1) lupus symptoms; (2) physical health (physical function, role physical); (3) pain-vitality; (4) emotional health (emotional function and role emotional); (5) body image; (6) cognition; (7) procreation; and (8) lupus medications. Non-HRQOL domains were (1) available social support and coping; (2) desires-goals; and (3) satisfaction with medical care. Internal consistency reliability (0.68-0.94), test-retest reliability (0.55-0.92), content, construct (r > 0.50 with SF-36), and criterion (r > -0.35 with disease activity) validity were fair to good. CONCLUSIONS: LupusPRO is a valid and reliable disease-targeted patient-reported health outcome tool that is generalizable to SLE patients in the United States of varied ethnic backgrounds and either gender.

Statistical implications of utility weighted and equally weighted HRQL measures: an empirical study.

The utility-based approach to health measurement, exemplified by EQ-5D and Health Utilities Index (HUI), has been challenged on a theoretical basis, but the statistical implications of such an approach have received little attention. To empirically investigate this issue, psychometric properties and statistical efficiency of the EQ-5D and HUI Mark 3 (HUI3) classifiers were compared when scored using preference weighted (WPS) and equally weighted summary scores using two longitudinal datasets (n(stroke)=124; n(rehabilitation)=264). Test-retest reliability, construct validity, responsiveness, and relative efficiency (RE) ratios (with bootstrapped 95% confidence intervals) were examined. WPS had slightly lower test-retest reliability, particularly for EQ-5D (intraclass correlation coefficient=0.61 vs 0.72). For known-groups comparisons, WPS had greater inferential power for both EQ-5D and HUI3 (RE>1). No significant differences in sensitivity to change were observed for EQ-5D [0.71 (95% CI: 0.29,1.33) < or = RE < or = 0.96(95% CI: 0.69,1.32)] or HUI3 [0.97 (95% CI: 0.89,1.03) < or = RE < or = 1.23 (95% CI: 0.98,1.72)]. Implications of weighted scoring will depend on whether the weights are greater or less than equal weights where patients fall along the health state classifier continuum. Because utility weights can affect the statistical properties and significance of results, the summary score selected should be appropriate to the purpose of the study and population of interest.

Psychometric properties of the EuroQol-5D and Short Form-6D in patients with systemic lupus erythematosus.

OBJECTIVE: Health related quality of life (HRQOL) is an important patient-reported outcome in systemic lupus erythematosus (SLE). We evaluated the psychometric properties of 2 widely used preference-based generic HRQOL measures, EuroQol-5D (EQ-5D) and Short Form-6D (SF-6D), among United States patients with SLE. METHODS: Patients with SLE enrolled at an academic institution were assessed for self-reported generic HRQOL (EQ-5D, Medical Outcomes Study SF-36), disease activity, and disease damage SF-6D. Physical Component Score (PCS) and Mental Component Score (MCS) were calculated from SF-36. Criterion validity, convergent validity, and known-groups comparisons were evaluated for EQ-5D and SF-6D. Sensitivity to change (t tests, effect size) was evaluated in a subset of the cohort followed longitudinally. RESULTS: One hundred sixty-seven patients with SLE were enrolled. Related domains on the EQ-5D and SF-36 correlated strongly, e.g., mobility and physical functioning (r=0.60), whereas unrelated domains showed weak to moderate correlation. EQ-5D index, EQ-5D visual analog scale, and SF-6D score correlated strongly among each other as well as with most domains of SF-36. Both EQ-5D and SF-6D indices differentiated among patients of varied disease severity. EQ-5D and SF-6D were found to be sensitive to self-reported change in health but insensitive to change in disease activity longitudinally. Disease activity and damage showed weak correlation with HRQOL measures. CONCLUSION: The SF-6D and EQ-5D exhibited satisfactory psychometric properties for use among US patients with SLE. Measures of disease activity and damage were weakly correlated with HRQOL, suggesting that HRQOL is an important complementary source of information about patients with SLE.

Economic evaluation of major knee surgery with recombinant activated factor VII in hemophilia patients with high titer inhibitors and advanced knee arthropathy: exploratory results via literature-based modeling.

OBJECTIVES: People with severe hemophilia suffer from frequent intra-articular hemorrhages, leading to pain, swelling, reduced flexion, and arthropathy. Elective orthopedic surgery using factor VIII (FVIII) replacement to prevent uncontrolled bleeding has been endorsed as an effective treatment option for patients with severe or advanced hemophilic arthropathy. These surgeries reduce pain, restore mobility and function, and reduce the frequency of recurrent joint bleeds. Unfortunately, some patients with hemophilia develop inhibitors to FVIII, which neutralize FVIII activity and render the use of even massive amounts of FVIII replacement ineffective and surgery very risky. For this reason, elective surgical procedures in high-titer inhibitor patients had largely been abandoned until the introduction of new agents, such as recombinant activated factor VII (rFVIIa, NovoSeven, Novo Nordisk A/S, Denmark). rFVIIa has been shown effective for prophylaxis during elective surgery and has therefore improved the feasibility of orthopedic surgery in hemophilia patients with high-titer inhibitors. The present research explored, from a modified US payer perspective, the direct economic and quality of life benefits of four different elective knee surgeries (total knee replacement [TKR], knee arthrodesis [KA], proximal tibial osteotomy, and distal femoral osteotomy) with rFVIIa coverage in hemophilia patients with high-titer inhibitors. METHODS: An exploratory literature-based life-table model was developed to compare the direct medical costs and quality of life of two hypothetical cohorts of high-titer inhibitor patients with frequent bleeding episodes: one undergoing and the other not undergoing elective knee surgery. Knee surgery costs included perioperative rFVIIa costs, inpatient and rehabilitation care, and repeat procedures due to surgery failure, prosthesis loosening or deep infection. Based on efficacy studies, knee surgery was assumed to reduce mean annual bleeding episodes at the affected joint from 9.13 to 1.64. The cost of managing each bleeding episode was estimated at $15 298. Thus, by reducing bleeding episodes, surgery was expected to result in related cost offsets. All costs were expressed in 2006 US dollars. Surgery was also assumed to result in gains in quality of life by reducing pain and reducing bleeding episodes. The impact of pain reduction on quality of life and utility was estimated by simulating EQ-5D scores for a typical patient with and without knee surgery. RESULTS: Based on the model, average knee surgery costs are predicted to range from a low of $694 000 (for KA) to a high of $855 000 (for TKR). However, knee surgery is also expected to reduce the subsequent number of bleeding episodes and resultant costs, leading to long-term costs savings. Due to improvement in pain levels, surgical patients are expected to experience improvements in quality-adjusted life-years (QALYs). Thus, surgery appears to be the preferred strategy (i.e., saves costs and increases QALYs). Based on the assumptions used in the model, the initial cost of knee surgery was offset during the 8th and 10th years for KA and TKR, respectively, with intermediate break-even time for the other surgeries. As expected, cost savings and gains in QALYs increased over time, as well as the cost effective ness of knee surgery. Specifically, the cost per QALY with KA and TKR fell under $50 000/QALY during the 6th and 8th years, respectively, with intermediate time for the other surgeries. CONCLUSIONS: The present exploratory analysis is based on the long-term extrapolation of data from a small number of patients without inhibitors and short-term studies. It suggests that major knee surgery utilizing rFVIIa in hemophilia patients with inhibitors may be cost-effective on average, with expected cost savings apparent within a decade of knee surgery. The present exploratory results should be validated with real-world, longitudinal patient data.

Health utilities using the EQ-5D in studies of cancer.

Cancer is one of the most frequent disease-specific applications of the EQ-5D. The objective of this review was to summarise evidence to support the validity and reliability of the EQ-5D in cancer, and to provide a catalogue of utility scores based on the use of the EQ-5D in clinical trials and in studies of patients with cancer. A structured literature search was conducted in EMBASE and MEDLINE to identify papers using key words related to cancer and the EQ-5D. Original research studies of patients with cancer that reported EQ-5D psychometric properties, responses and/or summary scores were included. Of 57 identified articles, 34 were selected for inclusion, where 12 studies reported evidence of validity or reliability and 31 reported EQ-5D responses or summary scores. The majority of investigations using the EQ-5D concerned patients with prostate cancer (n = 4), breast cancer (n = 4), cancers of the digestive system (n = 7) and Hodgkin and/or non-Hodgkin lymphoma (n = 3). Mean index-based scores ranged from 0.33 (SD 0.4) to 0.93 (SD 0.12) and visual analogue scale scores ranged from 43 (SD 13.3) to 84 (SD 12.0) across subtypes of cancer. A substantial and growing body of literature using the EQ-5D in cancer that supports the validity and reliability of EQ-5D in cancer has emerged. This review provides utility estimates for cancer patients across a wide range of cancer subtypes, treatment regimens and tumour stage(s) that may inform the modelling of outcomes in economic evaluations of cancer treatment.