Using a discrete choice experiment to value the QLU-C10D: feasibility and sensitivity to presentation format.

PURPOSE: To assess the feasibility of using a discrete choice experiment (DCE) to value health states within the QLU-C10D, a utility instrument derived from the QLQ-C30, and to assess clarity, difficulty, and respondent preference between two presentation formats. METHODS: We ran a DCE valuation task in an online panel (N = 430). Respondents answered 16 choice pairs; in half of these, differences between dimensions were highlighted, and in the remainder, common dimensions were described in text and differing attributes were tabulated. To simplify the cognitive task, only four of the QLU-C10D's ten dimensions differed per choice set. We assessed difficulty and clarity of the valuation task with Likert-type scales, and respondents were asked which format they preferred. We analysed the DCE data by format with a conditional logit model and used Chi-squared tests to compare other responses by format. Semi-structured telephone interviews (N = 8) explored respondents' cognitive approaches to the valuation task. RESULTS: Four hundred and forty-nine individuals were recruited, 430 completed at least one choice set, and 422/449 (94 %) completed all 16 choice sets. Interviews revealed that respondents found ten domains difficult but manageable, many adopting simplifying heuristics. Results for clarity and difficulty were identical between formats, but the "highlight" format was preferred by 68 % of respondents. Conditional logit parameter estimates were monotonic within domains, suggesting respondents were able to complete the DCE sensibly, yielding valid results. CONCLUSION: A DCE valuation task in which only four of the QLU-C10D's ten dimensions differed in any choice set is feasible for deriving utility weights for the QLU-C10D.

QLU-C10D: a health state classification system for a multi-attribute utility measure based on the EORTC QLQ-C30.

PURPOSE: To derive a health state classification system (HSCS) from the cancer-specific quality of life questionnaire, the EORTC QLQ-C30, as the basis for a multi-attribute utility instrument. METHODS: The conceptual model for the HSCS was based on the established domain structure of the QLQ-C30. Several criteria were considered to select a subset of dimensions and items for the HSCS. Expert opinion and patient input informed a priori selection of key dimensions. Psychometric criteria were assessed via secondary analysis of a pooled dataset comprising HRQOL and clinical data from 2616 patients from eight countries and a range of primary cancer sites, disease stages, and treatments. We used confirmatory factor analysis (CFA) to assess the conceptual model's robustness and generalisability. We assessed item floor effects (>75 % observations at lowest score), disordered item response thresholds, coverage of the latent variable and differential item function using Rasch analysis. We calculated effect sizes for known group comparisons based on disease stage and responsiveness to change. Seventy-nine cancer patients assessed the relative importance of items within dimensions. RESULTS: CFA supported the conceptual model and its generalisability across primary cancer sites. After considering all criteria, 12 items were selected representing 10 dimensions: physical functioning (mobility), role functioning, social functioning, emotional functioning, pain, fatigue, sleep, appetite, nausea, bowel problems. CONCLUSIONS: The HSCS created from QLQ-C30 items is known as the EORTC Quality of Life Utility Measure-Core 10 dimensions (QLU-C10D). The next phase of the QLU-C10D's development involves valuation studies, currently planned or being conducted across the globe.

United States Value Set for the Functional Assessment of Cancer Therapy-General Eight Dimensions (FACT-8D), a Cancer-Specific Preference-Based Quality of Life Instrument.

OBJECTIVES: To develop a value set reflecting the United States (US) general population's preferences for health states described by the Functional Assessment of Cancer Therapy (FACT) eight-dimensions preference-based multi-attribute utility instrument (FACT-8D), derived from the FACT-General cancer-specific health-related quality-of-life (HRQL) questionnaire. METHODS: A US online panel was quota-sampled to achieve a general population sample representative by sex, age (≥ 18 years), race and ethnicity. A discrete choice experiment (DCE) was used to value health states. The valuation task involved choosing between pairs of health states (choice-sets) described by varying levels of the FACT-8D HRQL dimensions and survival (life-years). The DCE included 100 choice-sets; each respondent was randomly allocated 16 choice-sets. Data were analysed using conditional logit regression parameterized to fit the quality-adjusted life-year framework, weighted for sociodemographic variables that were non-representative of the US general population. Preference weights were calculated as the ratio of HRQL-level coefficients to the survival coefficient. RESULTS: 2562 panel members opted in, 2462 (96%) completed at least one choice-set and 2357 (92%) completed 16 choice-sets. Pain and nausea were associated with the largest utility weights, work and sleep had more moderate utility weights, and sadness, worry and support had the smallest utility weights. Within dimensions, more severe HRQL levels were generally associated with larger weights. A preference-weighting algorithm to estimate US utilities from responses to the FACT-General questionnaire was generated. The worst health state's value was -0.33. CONCLUSIONS: This value set provides US population utilities for health states defined by the FACT-8D for use in evaluating oncology treatments.

The use of the EQ-5D preference-based health status measure in adults with Type 2 diabetes mellitus.

BACKGROUND: The EQ-5D is a generic preference-based health status measure that has been widely applied to measure the impact of Type 2 diabetes mellitus. This review summarizes evidence on the validity, reliability and responsiveness of the EQ-5D in studies of Type 2 diabetes and provides a catalogue of EQ-5D index scores for Type 2 diabetes and various complications and subgroups. METHODS: A structured search was conducted (1987-2009) using keywords relevant to Type 2 diabetes and the EQ-5D. Original research studies in Type 2 diabetes that reported EQ-5D results and/or measurement properties were included. RESULTS: Of the 59 included articles, 54 publications reported EQ-5D responses and 39 papers presented evidence on the measurement properties of the EQ-5D. Studies that reported measurement properties supported construct, convergent and discriminant validity, test-retest reliability and responsiveness of the EQ-5D in Type 2 diabetes. Several studies reported a ceiling effect for the EQ-5D and an inability to capture multiple complications was observed. EQ-5D index scores ranged from 0.20 (severe diabetic peripheral neuropathic pain) to 0.88 (general population: good HbA(1c) level). For six subgroups, sufficient studies were available to calculate pooled mean index scores (95% CI): general population 0.67 (0.59-0.75), no complications 0.76 (0.68-0.83), microvascular complications 0.73 (0.57-0.89), macrovascular complications 0.73 (0.57-0.88), diabetic peripheral neuropathic pain 0.45 (0.39-0.51) and retinopathy 0.57 (0.46-0.69). CONCLUSIONS: Evidence supported validity, reliability and responsiveness of the EQ-5D in Type 2 diabetes. EQ-5D index scores associated with Type 2 diabetes and various complications can be useful for modelling health outcomes in economic evaluations of health programmes for Type 2 diabetes.

Lupus-specific health outcome measure for US patients: the LupusQoL-US version.

BACKGROUND: Patient-reported outcomes are valuable for the management of chronic diseases like systematic lupus erythematosus (SLE), but no measures have been validated for use in US-based patients with SLE. OBJECTIVES: To adapt and assess the validity and reliability of an SLE-specific quality of life (QoL) measure developed in the United Kingdom, the LupusQoL, for use in US-based patients with SLE. METHODS: Debriefing interviews of subjects with SLE guided the language modifications of the tool. The LupusQoL-US, SF-36 and EQ5D were administered. Internal consistency (ICR) and test-retest (TRT) reliability, convergent and discriminative validity were examined. Factor analyses were performed. RESULTS: The mean (SD) age of the 185 subjects with SLE was 42.5 (12.9) years. ICR and TRT of the eight domains ranged from 0.85 to 0.94 and 0.68 to 0.92, respectively. Related domains on the SF-36 correlated with the LupusQoL domains (physical health and physical function r = 0.73, physical health and role physical r = 0.57, emotional health and mental health r = 0.72, emotional health and role emotional r = 0.48, pain and bodily pain r = 0.66, fatigue and vitality r = 0.70, planning and social functioning r = 0.58). Most LupusQoL-US domains could discriminate between subjects with varied disease activity and damage. Principal component analysis disclosed five factors in the US version, with physical function, pain and planning items loading on one factor. CONCLUSIONS: These data provide evidence to support the psychometric properties of the LupusQoL-US, suggesting its utility as an assessment tool for patients with SLE in the USA.

Drug utilization reviews of oral quinolone, cephalosporin, and macrolide use in nonacute care: a systematic review.

Drug utilization review (DUR) is a tool for monitoring the appropriateness of physicians' prescribing patterns. The present systematic overview was undertaken to determine the extent of appropriate use of oral quinolones, cephalosporins, and macrolides in nonacute-care settings in North America reported in published DUR studies. Potentially relevant DURs conducted since 1987 were retrieved from an electronic search of 6 databases (augmented by manual searches of bibliographies of appropriate articles) and from personal communications with local experts. Independent reviewers applied objective criteria to select the DURs for inclusion. Quality assessments were performed by 4 independent reviewers using the Edmonton Quality Assessment Tool for Drug Utilization Reviews, an instrument developed to assess the potential for systematic bias in a DUR. Data from the studies included were abstracted independently by 2 reviewers using a standard data-collection form. Twelve of 587 (2.0%) articles met the inclusion criteria. Eight studies targeted the appropriateness of prescriptions for ciprofloxacin (appropriateness range, 5% to 95%), 3 included cephalosporins (range, 0% to 100%), and 2 examined erythromycin (40%). There were 2 primary reasons for a rating of inappropriate: (1) the prescription was not first-line therapy, or (2) there was insufficient documentation in the patient record. The designation inappropriate did not mean that the drug did not benefit the patient. Of the 4 intervention-based DURs, 1 study showed a significant improvement in appropriate use. Because of heterogeneity in study design, delivery of interventions, and outcome assessment, a pooled estimate of effect was not derived. Four studies estimated the cost of inappropriate prescribing to the institutional study site, which ranged from $20,500 to $173,359 annually; however, these estimates cannot be generalized because of various limitations. When the 12 studies were assessed for methodologic quality, 1 study was rated as high, 7 as moderate, and 4 as low. Levels of prescribing appropriateness reported in the DUR literature should be interpreted cautiously. The DUR studies included in this review varied greatly in the methodologic rigor applied to sample selection, standardized data collection, application of standardized screening criteria, and validated data analysis.

Health status and satisfaction with pharmacy services.

OBJECTIVE: To evaluate the relationship between self-reported health status and satisfaction with pharmacy services. STUDY DESIGN: Secondary analysis of data previously collected via a computer-assisted telephone interview system. PATIENTS AND METHODS: Survey respondents were enrollees in a large managed care organization who were recent patrons of either traditional or mail pharmacy services. Satisfaction data were gathered using an existing satisfaction with pharmacy services survey. Health status was measured using the Medical Outcome Study's Short-Form 12-Item Health Survey. The relationships between satisfaction with pharmacy services and health status were analyzed using structural equation modeling. RESULTS: A significant positive relationship between mental health status and satisfaction with pharmacy services was hypothesized and confirmed. The correlations between mental health status and satisfaction, however, were not strong (r = .10 to .18). No relationship between physical health status and satisfaction with pharmacy services was observed. Similar results were observed in patrons of both traditional and mail pharmacy services. CONCLUSION: This investigation offers evidence that satisfaction with healthcare services is more closely related to mental health status than to physical health status. This has important implications for case-mix adjustments in the measurement of satisfaction with care.

Health-related quality of life in patients with advanced renal cell carcinoma receiving pazopanib or placebo in a randomised phase III trial.

BACKGROUND: In a double-blind, randomised phase III trial of advanced renal cell carcinoma patients, pazopanib 800mg QD (n=290) versus placebo (n=145) significantly prolonged progression-free survival (hazard ratio (HR)=0.46, 95% confidence interval [CI] 0.34-0.62, p-value<0.0001), without important differences in health-related quality of life (HRQoL). This post-hoc analysis evaluated time to HRQoL deterioration and whether tumour response/stabilisation was associated with HRQoL improvement. METHODS: HRQoL was assessed using EORTC QLQ-C30 and EQ-5D. Effect of pazopanib on time to ⩾20% decline from baseline in summary scores was estimated for all patients and by prior treatment. Analyses were conducted for different HRQoL deterioration thresholds. HRQoL changes were stratified by benefit and compared: complete response (CR) or partial response (PR) versus progressive disease (PD); CR/PR versus stable disease (SD), and SD versus PD. RESULTS: There was a trend for pazopanib patients to be less likely than placebo patients to experience ⩾20% HRQoL deterioration in EORTC-QLQ-C-30 global health status/QOL scale (HR=0.77; 95% CI 0.57-1.03, not significant). Results by prior treatment and different HRQoL deterioration thresholds were similar. Patients with CR/PR and SD experienced significantly less HRQoL deterioration than those with PD (p<0.001, p=0.0024, respectively); mean differences between patients with CR/PR and PD exceeded the pre-determined minimally important difference (MID). Differences between patients with SD and PD did not exceed pre-determined MID. Results were generally consistent across treatment and EQ-5D summary scores. CONCLUSION: Results support the favourable benefit-risk profile of pazopanib and suggest patients experiencing tumour response/stabilisation also may have better HRQoL compared to those without this response.

Prioritizing comparative-effectiveness research topics via stakeholder involvement: an application in COPD.

A major priority for funding agencies and researchers involved in comparative-effectiveness research (CER) is to ensure that research questions will produce findings that are relevant and feasible to implement. In this article, we describe a process for involving experts and stakeholders in identifying and prioritizing CER studies, as illustrated by our experience in chronic obstructive pulmonary disease (COPD).

Outcome, toxicity profile and cost analysis of autologous stem cell mobilization.

Autologous stem cell mobilization (ASCM) is conventionally done using high-dose CY plus granulocyte colony-stimulating factor (G). It is important to examine the outcomes, toxicity profile and costs of ASCM associated with CY+G. A retrospective study was conducted in 236 patients with myeloma or lymphoma undergoing ASCM with CY+G. An ideal outcome was defined as 2 × 10(6) CD34+ cells/kg collected on the planned day of collection in 1 or 2 apheresis without a negative clinical event. The total cost of ASCM including clinical events, were reported based on Medicare part-B physician, laboratory and ancillary fee schedule. ASCM was successful in 213 (90%) patients, but an ideal outcome was seen in only 50 (20%) patients. Median (interquartile range, IQR) total cost of CY+G stem cells mobilization was $10,605 ($9,230-$14,540). Ideal outcomes were associated with lower costs compared with non-ideal outcomes (median (IQR), $9914 ($8,743-$11,168) versus $11232 ($9,292-$15,518) respectively, P<0.001). The median (IQR) cost of non-ideal outcome was higher among lymphoma patients ($12,293 ($9578-$16,268)) compared with myeloma patients ($10,388 ($9,355-$14,360) (P=0.04). Although mobilization success is eventually realized with CY+G, it has a low rate of ideal outcome, associated with significant adverse events and costs.

Comparison of the EQ-5D and SF-12 health surveys in a general population survey in Alberta, Canada.

OBJECTIVES: The purposes of this analysis were to evaluate the construct validity of the EQ-5D and compare responses on the EQ-5D with the Physical Component Summary (PCS-12) and Mental Component Summary (MCS-12) scores of the SF-12 Health Survey. METHODS: Data were collected via a survey instrument mailed to 4,200 randomly selected subjects in the province of Alberta, Canada. The instrument contained the EQ-5D and SF-12 health surveys, with additional questions eliciting clinical and demographic information from the respondents. RESULTS: 1,555 respondents returned mailed questionnaires; 606 questionnaires were returned undeliverable. The SF-12 summary scores were calculated for 1,380 respondents. Analysis of the EQ-5D responses by demographic variables found significant differences among categories of age, gender, and self-reported chronic medical conditions. Corresponding dimensions and summary scores were more strongly related (eg, mobility and PCS-12; F ratio = 598.3, P < 0.001) than dissimilar dimensions (eg, mobility and MCS-12; F ratio = 18.8, P < 0.001). The EQ-5D index scores were moderately correlated with SF-12 summary scores (r = 0.41 for MCS-12 and r = 0.68 for PCS-12). For subjects reporting no problems on the EQ-5D, PCS-12 and MCS-12 scores were significantly lower for people reporting medical problems or feelings of depression. CONCLUSIONS: The results of this investigation generally supported the validity of the EQ-5D. However, an important ceiling effect was observed for the EQ-5D in this sample. The combination of the EQ-5D and SF-12 provides relatively broad coverage of important health domains and scores for various purposes.

Edmonton Quality Assessment Tool for Drug Utilization Reviews: EQUATDUR-2: the development of a scale to assess the methodological quality of a drug utilization review.

OBJECTIVE: The objective of this study was to develop an instrument that will assist in evaluating the methodological quality of drug utilization reviews (DURs) and studies of prescribing appropriateness. DESIGN: An expert committee followed accepted steps for developing and testing new instruments. Consultations on content, face validity, and scoring of items were solicited from external experts. Seven raters tested an initial version; subsequently, a refined instrument was designed. The Edmonton Quality Assessment Tool for Drug Utilization Reviews (EQUATDUR-2) evaluates 3 domains: sample selection (1 item), data collection (1 item), and data analysis (3 items). Sixteen raters tested EQUATDUR-2 on a random sample of DURs. MEASURES: The study measures were reliability-using random effects interclass correlation coefficients for ratings by individual raters (ICC2,1) and the mean of ratings (ICC2,k)-and variability between DUR quality levels and rater groups. RESULTS: There were significant differences in methodological quality (P <0.001) and in mean scores comparing low-, moderate-, and high-quality DURs. Nonmethodologists' ratings exhibited significant variability (P = 0.03) and tended to be higher. Agreement varied for individual items (ICC2,1, 0.22 to 0.44; ICC2,k, 0.81 to 0.91) and for mean summary ratings (ICC2,1, 0.42 [95% CI, 0.28 to 0.61]; ICC2,k, 0.92 [95% CI, 0.86 to 0.96]). The average time to rate each DUR was 10.0 minutes (95% CI, 9.2 to 10.9). CONCLUSIONS: EQUATDUR-2 is a succinct, self-administered instrument with evidence of validity and reliability. We recommend that > or =2 raters independently assess each DUR and resolve disagreements by consensus. EQUATDUR-2 will help clinicians and decision makers to evaluate the quality of DUR studies and provide a framework for enhancing rigor in the design, conduct, and reporting of DURs.

The impact of pharmacist interventions on health-related quality of life.

OBJECTIVE: To describe and evaluate pharmacy practice-based studies that include health-related quality of life (HRQL) as an outcome measure in assessments of pharmacist interventions and to recommend approaches for incorporating HRQL as a patient outcome in pharmacy practice-based intervention studies. METHODS: Citations were identified in MEDLINE, Healthstar, EMBASE, and International Pharmaceutical Abstracts from January 1988 to February 1999 using terms for health-related quality of life and pharmacist interventions. Abstracts were screened by two reviewers and articles that reported a pharmacist intervention performed with HRQL as an outcome measure were included. RESULTS: Of 689 citations identified by the literature search terms, 11 met the inclusion criteria. Nine studies contained a disease-specific focus. The SF-36, or its variations, was the only generic instrument used, and seven studies described using a disease-specific instrument. Pharmacist interventions inconsistently demonstrated positive effects on patient HRQL. DISCUSSION: Possible reasons for not detecting significant differences in HRQL include length of study period, insufficient sample size and power, selection bias, labeling effects, the type of measure applied, and lack of actual influence of pharmaceutical services on HRQL. Strategies to strengthen the design and methodologic approach, such as the reporting of effect size, are recommended. CONCLUSIONS: In order to demonstrate the positive effect of pharmaceutical services on patient health, pharmacy practice researchers should continue incorporating HRQL outcome measures, complemented by clinical, economic, and other humanistic outcome indicators.

Replicability of SF-36 summary scores by the SF-12 in stroke patients.

BACKGROUND AND PURPOSE: The replicability of the physical and mental component summary scores of the Short Form (SF)-36 has been established using the SF-12 in selected patient populations but has yet to be assessed in stroke patients. If the summary scores of the SF-12 are highly correlated with those of the SF-36, the benefits of using a shorter health-status measure may be realized without substantial loss of information or precision. Both self-reported and proxy assessments were evaluated for replicability. METHODS: Intraclass correlation coefficients (ICCs) and linear regression were used to assess the ability of the SF-12 physical component summary (PCS-12) scores to predict PCS-36 scores and the SF-12 mental component summary (MCS-12) scores to predict MCS-36 scores. Multivariate regression was used to explore the relationship between SF-12 and SF-36 scores. RESULTS: The MCS-12 and PCS-12 scores were strongly correlated with the corresponding SF-36 summary scores for surveys completed by proxy or self-report (ICCs ranged from 0.954 to 0.973). Regression analysis of the proxy assessments indicated that patient age was an important effect modifier in the relationship between MCS-12 and MCS-36 scores. CONCLUSIONS: The SF-12 reproduced SF-36 summary scores without substantial loss of information in stroke patients. Accordingly, the SF-12 can be used at the summary score level as a substitute for the SF-36 in stroke survivors capable of self-report. However, the mental health summary scores of proxy assessments are influenced by patient age, thereby limiting the replicability of the SF-36 by the SF-12 under these conditions.