Overlap of Depressive Symptoms with Health-Related Quality-of-Life Measures.

Because depressive symptoms are a part of health-related quality-of-life (HRQOL) measures, measures of depression will be empirically associated with HRQOL. We discuss examples of published research where authors ignored or did not fully account for overlap between depressive symptom and HRQOL measures. Future researchers need to recognize when their models include conceptually similar variables on the same side or both sides of the equation. This awareness will lead to more accurate conclusions about the prognostic value of depression and other HRQOL measures for health care utilization, mortality, and other outcomes. It will also result in fewer incorrect claims about the effect of depression on HRQOL.

Do the unlabeled response categories of the Minnesota Living with Heart Failure Questionnaire satisfy the monotonicity assumption of simple-summated scoring?

PURPOSE: Half of the 21-item Minnesota Living with Heart Failure Questionnaire (MLHFQ) response categories are labeled (0 = No, 1 = Very little, 5 = Very much) and half are not (2, 3, and 4). We hypothesized that the unlabeled response options would not be more likely to be chosen at some place along the scale continuum than other response options and, therefore, not satisfy the monotonicity assumption of simple-summated scoring. METHODS: We performed exploratory and confirmatory factor analyses of the MLHFQ items in a sample of 1437 adults in the Better Effectiveness After Transition-Heart Failure study. We evaluated the unlabeled response options using item characteristic curves from item response theory-graded response models for MLHFQ physical and emotional health scales. Then, we examined the impact of collapsing response options on correlations of scale scores with other variables. RESULTS: The sample was 46% female; 71% aged 65 or older; 11% Hispanic, 22% Black, 54% White, and 12% other. The unlabeled response options were rarely chosen. The standard approach to scoring and scores obtained by collapsing adjacent response categories yielded similar associations with other variables, indicating that the existing response options are problematic. CONCLUSIONS: The unlabeled MLHFQ response options do not meet the assumptions of simple-summated scoring. Further assessment of the performance of the unlabeled response options and evaluation of alternative scoring approaches is recommended. Adding labels for response options in future administrations of the MLHFQ should be considered.

An international study of the quality of life of adult patients treated with home parenteral nutrition.

BACKGROUND & AIMS: Home parenteral nutrition-quality of life (HPN-QOL©) is a self-assessment tool for the measurement of QOL in patients on HPN. The aims of this study were: to re-assess the basic psychometric properties of the HPN-QOL© in a multinational sample of adult patients; to provide a description of QOL dimensions by short and long HPN treatment duration; to explore clinical factors potentially associated to QOL scores. METHODS: Patients (n = 699) from 14 countries completed the HPN-QOL©. The questionnaires were analysed to evaluate data completeness, convergent/discriminant validity and internal-consistency reliability. The association of overall QOL and HPN treatment duration as well as other clinical factors were investigated using multivariable linear regression models. RESULTS: The analysis of the multitrait-scaling and internal consistency indicates a good fit with the questionnaire structure for most items. Item discriminant validity correlation was satisfactory and psychometric evaluation of the HPN-QOL© in the different English, French and Italian language patient sub-groups confirmed psychometric equivalence of the three questionnaire versions. The results of the multivariable linear regression showed that QOL scores were significantly associated with HPN duration (better in long-term), underlying disease (better in Crohn's disease and mesenteric ischaemia) and living status (worse in living alone) and, after adjusting for the other factors, with the number of days of HPN infusion per week. CONCLUSIONS: The HPN-QOL©, is a valid tool for measurement of QOL in patients on HPN, to be used in the clinical practice as well as in research.

Australian Utility Weights for the EORTC QLU-C10D, a Multi-Attribute Utility Instrument Derived from the Cancer-Specific Quality of Life Questionnaire, EORTC QLQ-C30.

BACKGROUND: The EORTC QLU-C10D is a new multi-attribute utility instrument derived from the widely used cancer-specific quality-of-life (QOL) questionnaire, EORTC QLQ-C30. The QLU-C10D contains ten dimensions (Physical, Role, Social and Emotional Functioning; Pain, Fatigue, Sleep, Appetite, Nausea, Bowel Problems), each with four levels. To be used in cost-utility analysis, country-specific valuation sets are required. OBJECTIVE: The aim of this study was to provide Australian utility weights for the QLU-C10D. METHODS: An Australian online panel was quota-sampled to ensure population representativeness by sex and age (≥ 18 years). Participants completed a discrete choice experiment (DCE) consisting of 16 choice-pairs. Each pair comprised two QLU-C10D health states plus life expectancy. Data were analysed using conditional logistic regression, parameterised to fit the quality-adjusted life-year framework. Utility weights were calculated as the ratio of each QOL dimension-level coefficient to the coefficient on life expectancy. RESULTS: A total of 1979 panel members opted in, 1904 (96%) completed at least one choice-pair, and 1846 (93%) completed all 16 choice-pairs. Dimension weights were generally monotonic: poorer levels within each dimension were generally associated with greater utility decrements. The dimensions that impacted most on choice were, in order, Physical Functioning, Pain, Role Functioning and Emotional Functioning. Oncology-relevant dimensions with moderate impact were Nausea and Bowel Problems. Fatigue, Trouble Sleeping and Appetite had relatively small impact. The value of the worst health state was -0.096, somewhat worse than death. CONCLUSIONS: This study provides the first country-specific value set for the QLU-C10D, which can facilitate cost-utility analyses when applied to data collected with the EORTC QLQ-C30, prospectively and retrospectively.

Sensitivity and responsiveness of the patient-reported TED-QOL to rehabilitative surgery in thyroid eye disease.

We tested the sensitivity and responsiveness of the TED-QOL to rehabilitative surgery in thyroid eye disease (TED). The 3-item TED-QOL and 16-item GO-QOL, which assess quality of life (QoL) in TED, were administered to consecutive patients undergoing rehabilitative surgery. The questionnaires were completed pre-and post-operatively to assess sensitivity (ability to discriminate between different surgical groups) and responsiveness (ability to detect within patient changes over time).56 patients underwent 69 procedures for TED (29 orbital decompressions, 15 strabismus operations, 25 eyelid procedures). The differences in scores between the three types of surgery (a measure of sensitivity) were statistically significant at the 5% level pre-operatively and post-operatively for all 3 TED-QOL scales and for both GO-QOL scales, but much more so for the TED-QOL scales in each case. The within-patient changes between the pre- and post-operative scores for the same subjects (a measure of responsiveness) were statistically very highly significant for the TED-QOL overall and appearance scales for each of the surgeries. The pre- and post-operative difference for the TED-QOL functioning scale was highly statistically significant for strabismus surgery but not for decompression or lid surgery. The change between the pre- and post-operative scores for the GO-QOL was significant for the functioning scale with strabismus and lid surgery, and was highly significant for the appearance scale with lid surgery but not for strabismus surgery or decompression. The 3-item TED-QOL is sensitive and responsive to rehabilitative surgery in TED and compares favorably with the lengthier GO-QOL for these parameters.

The Edmonton Symptom Assessment System: Poor performance as screener for major depression in patients with incurable cancer.

BACKGROUND: Depressive symptoms are prevalent in patients with advanced cancer, sometimes of a severity that fulfil the criteria for a major depressive episode. AIM: The aim of this study was to investigate how the item on depression in the Edmonton Symptom Assessment System with a 0-10 Numerical Rating Scale performed as a screener for major depressive episode. A possible improved performance by adding the Edmonton Symptom Assessment System-Anxiety item was also examined. DESIGN: An international cross-sectional study including patients with incurable cancer was conducted. The Edmonton Symptom Assessment System score was compared against major depressive episode as assessed by the Patient Health Questionnaire-9. Screening performance was examined by sensitivity, specificity and the kappa coefficient. SETTING: Patients with incurable cancer (n = 969), median age 63 years and from eight nationalities provided report. Median Karnofsky Performance Status was 70. Median survival was 229 days (205-255 days). RESULTS: Patient Health Questionnaire-9 major depressive episode was present in 133 of 969 patients (13.7%). Edmonton Symptom Assessment System-Depression screening ability for Patient Health Questionnaire-9 major depressive episode was limited. Area under the receiver operating characteristic curve was 0.71 (0.66-0.76). Valid detection or exclusion of Patient Health Questionnaire-9 major depressive episode could not be concluded at any Edmonton Symptom Assessment System-Depression cut-off; by the cut-off Numerical Rating Scale ⩾ 2, sensitivity was 0.69 and specificity was 0.60. By the cut-off Numerical Rating Scale ⩾ 4, sensitivity was 0.51 and specificity was 0.82. Combined mean ratings by Edmonton Symptom Assessment System-Depression and Edmonton Symptom Assessment System-Anxiety revealed similar limited screening ability. CONCLUSION: The depression and anxiety items of the Edmonton Symptom Assessment System, a frequently used assessment tool in palliative care settings, seem to measure a construct other than major depressive episode as assessed by the Patient Health Questionnaire-9 instrument.

Replication and validation of higher order models demonstrated that a summary score for the EORTC QLQ-C30 is robust.

OBJECTIVE: To further evaluate the higher order measurement structure of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30), with the aim of generating a summary score. STUDY DESIGN AND SETTING: Using pretreatment QLQ-C30 data (N = 3,282), we conducted confirmatory factor analyses to test seven previously evaluated higher order models. We compared the summary score(s) derived from the best performing higher order model with the original QLQ-C30 scale scores, using tumor stage, performance status, and change over time (N = 244) as grouping variables. RESULTS: Although all models showed acceptable fit, we continued in the interest of parsimony with known-groups validity and responsiveness analyses using a summary score derived from the single higher order factor model. The validity and responsiveness of this QLQ-C30 summary score was equal to, and in many cases superior to the original, underlying QLQ-C30 scale scores. CONCLUSION: Our results provide empirical support for a measurement model for the QLQ-C30 yielding a single summary score. The availability of this summary score can avoid problems with potential type I errors that arise because of multiple testing when making comparisons based on the 15 outcomes generated by this questionnaire and may reduce sample size requirements for health-related quality of life studies using the QLQ-C30 questionnaire when an overall summary score is a relevant primary outcome.

Symptom Clusters in Advanced Cancer Patients: An Empirical Comparison of Statistical Methods and the Impact on Quality of Life.

CONTEXT: Symptom clusters in advanced cancer can influence patient outcomes. There is large heterogeneity in the methods used to identify symptom clusters. OBJECTIVES: To investigate the consistency of symptom cluster composition in advanced cancer patients using different statistical methodologies for all patients across five primary cancer sites, and to examine which clusters predict functional status, a global assessment of health and global quality of life. METHODS: Principal component analysis and exploratory factor analysis (with different rotation and factor selection methods) and hierarchical cluster analysis (with different linkage and similarity measures) were used on a data set of 1562 advanced cancer patients who completed the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. RESULTS: Four clusters consistently formed for many of the methods and cancer sites: tense-worry-irritable-depressed (emotional cluster), fatigue-pain, nausea-vomiting, and concentration-memory (cognitive cluster). The emotional cluster was a stronger predictor of overall quality of life than the other clusters. Fatigue-pain was a stronger predictor of overall health than the other clusters. The cognitive cluster and fatigue-pain predicted physical functioning, role functioning, and social functioning. CONCLUSIONS: The four identified symptom clusters were consistent across statistical methods and cancer types, although there were some noteworthy differences. Statistical derivation of symptom clusters is in need of greater methodological guidance. A psychosocial pathway in the management of symptom clusters may improve quality of life. Biological mechanisms underpinning symptom clusters need to be delineated by future research. A framework for evidence-based screening, assessment, treatment, and follow-up of symptom clusters in advanced cancer is essential.

Is progression-free survival associated with a better health-related quality of life in patients with lung cancer? Evidence from two randomised trials with afatinib.

OBJECTIVE: Progression-free survival (PFS) is frequently used as an efficacy end point in oncology clinical trials. However, there is limited evidence to support a positive association between improvement in PFS and improvement in health-related quality of life (HRQoL). The association between PFS and HRQoL was evaluated in two randomised trials. MATERIALS AND METHODS: Data from two randomised controlled trials in patients with non-small cell lung cancer (NSCLC; LUX-Lung 1 and LUX-Lung 3) were used to investigate HRQoL in patients to determine whether tumour progression is accompanied by worsening HRQoL. HRQoL was assessed using the cancer-specific European Organization for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30, the EuroQol EQ-5D overall utility and EuroQol EQ visual analogue scale. In both studies, progression was evaluated by independent review using RECIST criteria (primary end point) and also by investigator assessment. The relationship between tumour progression and HRQoL was evaluated using analysis of covariance and a longitudinal model. RESULTS: Compliance with HRQoL questionnaire completion was high. In both studies, patients with progression consistently experienced numerically poorer HRQoL at the time of progression than patients without progression. Differences in mean scores were statistically significant (p<0.05) between patients with and without progression at week 4 in all analyses in LUX-Lung 1 and at multiple time points in LUX-Lung 3. Results from the longitudinal analysis showed that progression (by independent review and investigator assessment) appears to have consistent negative impact on all three HRQoL measures (all p<0.0001). CONCLUSIONS: Tumour progression in patients with NSCLC was associated with statistically significant worsening in HRQoL. These findings confirm the value of PFS as a patient-relevant end point.

Deriving a preference-based utility measure for cancer patients from the European Organisation for the Research and Treatment of Cancer's Quality of Life Questionnaire C30: a confirmatory versus exploratory approach.

BACKGROUND: Multi attribute utility instruments (MAUIs) are preference-based measures that comprise a health state classification system (HSCS) and a scoring algorithm that assigns a utility value to each health state in the HSCS. When developing a MAUI from a health-related quality of life (HRQOL) questionnaire, first a HSCS must be derived. This typically involves selecting a subset of domains and items because HRQOL questionnaires typically have too many items to be amendable to the valuation task required to develop the scoring algorithm for a MAUI. Currently, exploratory factor analysis (EFA) followed by Rasch analysis is recommended for deriving a MAUI from a HRQOL measure. AIM: To determine whether confirmatory factor analysis (CFA) is more appropriate and efficient than EFA to derive a HSCS from the European Organisation for the Research and Treatment of Cancer's core HRQOL questionnaire, Quality of Life Questionnaire (QLQ-C30), given its well-established domain structure. METHODS: QLQ-C30 (Version 3) data were collected from 356 patients receiving palliative radiotherapy for recurrent/metastatic cancer (various primary sites). The dimensional structure of the QLQ-C30 was tested with EFA and CFA, the latter informed by the established QLQ-C30 structure and views of both patients and clinicians on which are the most relevant items. Dimensions determined by EFA or CFA were then subjected to Rasch analysis. RESULTS: CFA results generally supported the proposed QLQ-C30 structure (comparative fit index =0.99, Tucker-Lewis index =0.99, root mean square error of approximation =0.04). EFA revealed fewer factors and some items cross-loaded on multiple factors. Further assessment of dimensionality with Rasch analysis allowed better alignment of the EFA dimensions with those detected by CFA. CONCLUSION: CFA was more appropriate and efficient than EFA in producing clinically interpretable results for the HSCS for a proposed new cancer-specific MAUI. Our findings suggest that CFA should be recommended generally when deriving a preference-based measure from a HRQOL measure that has an established domain structure.

Should linking replace regression when mapping from profile-based measures to preference-based measures?

BACKGROUND: Profile instruments are frequently used to assess health-related quality of life and other patient-reported outcomes. However, preference-based measures are required for health-economic cost-utility evaluations. RESULTS: Although regression-based approaches are commonly used to map from profile measures to preference measures, we show that this results in biased estimates because of regression to the mean. CONCLUSIONS: Linking (scale-aligning) is proposed as an alternative.

Use of methods for specifying the target difference in randomised controlled trial sample size calculations: Two surveys of trialists' practice.

BACKGROUND: Central to the design of a randomised controlled trial (RCT) is a calculation of the number of participants needed. This is typically achieved by specifying a target difference, which enables the trial to identify a difference of a particular magnitude should one exist. Seven methods have been proposed for formally determining what the target difference should be. However, in practice, it may be driven by convenience or some other informal basis. It is unclear how aware the trialist community is of these formal methods or whether they are used. PURPOSE: To determine current practice regarding the specification of the target difference by surveying trialists. METHODS: Two surveys were conducted: (1) Members of the Society for Clinical Trials (SCT): participants were invited to complete an online survey through the society's email distribution list. Respondents were asked about their awareness, use of, and willingness to recommend methods; (2) Leading UK- and Ireland-based trialists: the survey was sent to UK Clinical Research Collaboration registered Clinical Trials Units, Medical Research Council UK Hubs for Trial Methodology Research, and the Research Design Services of the National Institute for Health Research. This survey also included questions about the most recent trial developed by the respondent's group. RESULTS: Survey 1: Of the 1182 members on the SCT membership email distribution list, 180 responses were received (15%). Awareness of methods ranged from 69 (38%) for health economic methods to 162 (90%) for pilot study. Willingness to recommend among those who had used a particular method ranged from 56% for the opinion-seeking method to 89% for the review of evidence-base method. Survey 2: Of the 61 surveys sent out, 34 (56%) responses were received. Awareness of methods ranged from 33 (97%) for the review of evidence-base and pilot methods to 14 (41%) for the distribution method. The highest level of willingness to recommend among users was for the anchor method (87%). Based upon the most recent trial, the target difference was usually one viewed as important by a stakeholder group, mostly also viewed as a realistic difference given the interventions under evaluation, and sometimes one that led to an achievable sample size. LIMITATIONS: The response rates achieved were relatively low despite the surveys being short, well presented, and having utilised reminders. CONCLUSION: Substantial variations in practice exist with awareness, use, and willingness to recommend methods varying substantially. The findings support the view that sample size calculation is a more complex process than would appear to be the case from trial reports and protocols. Guidance on approaches for sample size estimation may increase both awareness and use of appropriate formal methods.

Don't middle your MIDs: regression to the mean shrinks estimates of minimally important differences.

Minimal important differences (MIDs) for patient-reported outcomes (PROs) are often estimated by selecting a clinical variable to serve as an anchor. Then, differences in the clinical anchor regarded as clinically meaningful or important can be used to estimate the corresponding value of the PRO. Although these MID values are sometimes estimated by regression techniques, we show that this is a biased procedure and should not be used; alternative methods are proposed.

Weight loss, appetite loss and food intake in cancer patients with cancer cachexia: three peas in a pod? - analysis from a multicenter cross sectional study.

BACKGROUND: How to assess cachexia is a barrier both in research and in clinical practice. This study examines the need for assessing both reduced food intake and loss of appetite, to see if these variables can be used interchangeably. A secondary aim is to assess the variance explained by food intake, appetite and weight loss by using tumor-related factors, symptoms and biological markers as explanatory variables. MATERIAL AND METHODS: One thousand and seventy patients with incurable cancer were registered in an observational, cross sectional multicenter study. A total of 885 patients that had complete data on food intake (PG-SGA), appetite (EORTC QLQ-C30) and weight loss were included in the present analysis. The association between reduced food intake and appetite loss was assessed using Spearman's correlation. To find the explained variance of the three symptoms a multivariate analysis was performed. RESULTS: The mean age was 62 years with a mean survival of 247 days and a mean Karnofsky performance status of 72. Thirteen percent of the patients who reported eating less than normal had good appetite and 25% who had unchanged or increased food intake had reduced appetite. Correlation between appetite loss and food intake was 0.50. Explained variance for the regression models was 44% for appetite loss, 27% for food intake and only 13% for weight loss. CONCLUSION: Both appetite loss and food intake should be assessed in cachectic patients since conscious control of eating may sometimes overcome appetite loss. The low explained variance for weight loss is probably caused by the need for more knowledge about metabolism and inflammation, and is consistent with the cancer cachexia definition that claims that in cachexia weight loss is not caused by reduced food intake alone. The questions concerning appetite loss from EORTC-QLQ C30 and food intake from PG-SGA seem practical and informative when dealing with advanced cancer patients.

ISOQOL recommends minimum standards for patient-reported outcome measures used in patient-centered outcomes and comparative effectiveness research.

PURPOSE: An essential aspect of patient-centered outcomes research (PCOR) and comparative effectiveness research (CER) is the integration of patient perspectives and experiences with clinical data to evaluate interventions. Thus, PCOR and CER require capturing patient-reported outcome (PRO) data appropriately to inform research, healthcare delivery, and policy. This initiative's goal was to identify minimum standards for the design and selection of a PRO measure for use in PCOR and CER. METHODS: We performed a literature review to find existing guidelines for the selection of PRO measures. We also conducted an online survey of the International Society for Quality of Life Research (ISOQOL) membership to solicit input on PRO standards. A standard was designated as "recommended" when >50 % respondents endorsed it as "required as a minimum standard." RESULTS: The literature review identified 387 articles. Survey response rate was 120 of 506 ISOQOL members. The respondents had an average of 15 years experience in PRO research, and 89 % felt competent or very competent providing feedback. Final recommendations for PRO measure standards included: documentation of the conceptual and measurement model; evidence for reliability, validity (content validity, construct validity, responsiveness); interpretability of scores; quality translation, and acceptable patient and investigator burden. CONCLUSION: The development of these minimum measurement standards is intended to promote the appropriate use of PRO measures to inform PCOR and CER, which in turn can improve the effectiveness and efficiency of healthcare delivery. A next step is to expand these minimum standards to identify best practices for selecting decision-relevant PRO measures.

An evaluation of the response category translations of the EORTC QLQ-C30 questionnaire.

PURPOSE: The aim of this study was to evaluate the translated response categories used in eight translations of the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire, which is used in many international clinical trials. Twenty-eight of the 30 items in the questionnaire have the same four response categories: "Not at all", "A little", "Quite a bit" and "Very Much". METHODS: People with knowledge of both English and one of eight European languages were asked to complete an Internet survey. The strength (intensity) of the translated categories was assessed using two separate approaches: one using a verbal response scale and the other a visual analogue scale (VAS). RESULTS: Two hundred and seventy-nine people participated in the survey. Most translations were rated similarly to English. The largest differences were for the German translation of "Quite a bit", which was rated 16.3 points lower than the corresponding English category on a 0-100 VAS. CONCLUSIONS: Most of the translated categories were found to be similar to the English versions and should continue to be used. We recommend that three translated categories should be considered for revision. Similar surveys could be used to assess the categories used in other translated quality of life instruments.

Is there a genetic cause of appetite loss?-an explorative study in 1,853 cancer patients.

BACKGROUND: Appetite loss has a major impact on cancer patients. It is exceedingly prevalent, is a prognostic indicator and is associated with inferior quality of life. Cachexia is a multi-factorial syndrome defined by a negative protein and energy balance, driven by a variable combination of reduced food intake and abnormal metabolism. Not all cancer patients that experience weight loss have appetite loss, and the pathophysiology between cachexia and appetite loss may thus be different. Knowledge of pathophysiology of appetite loss in cancer patients is still limited. The primary object of this study was to explore the association with 93 predefined candidate single-nucleotide polymorphisms (SNPs) and appetite loss in cancer patients to possibly generate new theories of the pathophysiology of the condition. METHODS: A total of 1,853 cancer patients were phenotyped according to appetite loss and then genotyped. RESULTS: After allowing for multiple testing, there was no statistically significant association between any of the SNPs analysed and appetite loss. The ten most significant SNPs in the co-dominant model had observed odds ratios varying from 0.72 to 1.28. CONCLUSIONS: This large exploratory study could not find any associations with loss of appetite and 93 SNPs with a potential to be involved in appetite loss in cancer patients. This does not however rule out genes putative role in the development of the symptom, but the observed odds ratios are close to one which makes it unlikely that any of the individual SNPs explored in the present study have great importance.

Comparing higher order models for the EORTC QLQ-C30.

PURPOSE: To investigate the statistical fit of alternative higher order models for summarizing the health-related quality of life profile generated by the EORTC QLQ-C30 questionnaire. METHODS: A 50% random sample was drawn from a dataset of more than 9,000 pre-treatment QLQ-C30 v 3.0 questionnaires completed by cancer patients from 48 countries, differing in primary tumor site and disease stage. Building on a "standard" 14-dimensional QLQ-C30 model, confirmatory factor analysis was used to compare 6 higher order models, including a 1-dimensional (1D) model, a 2D "symptom burden and function" model, two 2D "mental/physical" models, and two models with a "formative" (or "causal") formulation of "symptom burden," and "function." RESULTS: All of the models considered had at least an "adequate" fit to the data: the less restricted the model, the better the fit. The RMSEA fit indices for the various models ranged from 0.042 to 0.061, CFI's 0.90-0.96, and TLI's from 0.96 to 0.98. All chi-square tests were significant. One of the Physical/Mental models had fit indices superior to the other models considered. CONCLUSIONS: The Physical/Mental health model had the best fit of the higher order models considered, and enjoys empirical and theoretical support in comparable instruments and applications.

Responsiveness and minimal important score differences in quality-of-life questionnaires: a comparison of the EORTC QLQ-C30 cancer-specific questionnaire to the generic utility questionnaires EQ-5D and 15D in patients with multiple myeloma.

OBJECTIVES: The aims of this study were to (i) compare the responsiveness of the EORTC QLQ-C30 cancer-specific questionnaire and the generic questionnaires EQ-5D and 15D used for economic evaluation of healthcare interventions and (ii) determine the minimal important differences (MIDs) in these questionnaires. The MID is the smallest change in a quality-of-life score considered important to patients. METHODS: Between 2006 and 2008, 239 patients with multiple myeloma completed the questionnaires at inclusion (T1) and after 3 months (T2). At T2, patients were asked whether they had noticed any change in their quality of life. Responsiveness and MIDs were determined by mean score changes (T2-T1) for patients who, in the interview, stated they had improved, deteriorated, or were unchanged. Responsiveness was also assessed using standardized response means. Wilcoxon tests for pair differences were used to evaluate the statistical significance of the changes. RESULTS: Patients who improved had significantly (P < 0.01) higher scores at T2 in all three questionnaires. Patients who deteriorated reported lower scores at T2; however, for the 15D, the differences in score were not statistically significant. The MIDs for the QLQ-C30, EQ-5D, and 15D were 8, 0.08, and 0.03 in patients who improved and 12, 0.10 and 0.02 in patients who deteriorated, respectively. CONCLUSIONS: All three questionnaires showed an acceptable responsiveness in patients who improved. However, the 15D did not respond optimally in patients who deteriorate and cannot be recommended for use in patients with myeloma.

Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials.

The role of thalidomide for previously untreated elderly patients with multiple myeloma remains unclear. Six randomized controlled trials, launched in or after 2000, compared melphalan and prednisone alone (MP) and with thalidomide (MPT). The effect on overall survival (OS) varied across trials. We carried out a meta-analysis of the 1685 individual patients in these trials. The primary endpoint was OS, and progression-free survival (PFS) and 1-year response rates were secondary endpoints. There was a highly significant benefit to OS from adding thalidomide to MP (hazard ratio = 0.83; 95% confidence interval 0.73-0.94, P = .004), representing increased median OS time of 6.6 months, from 32.7 months (MP) to 39.3 months (MPT). The thalidomide regimen was also associated with superior PFS (hazard ratio = 0.68, 95% confidence interval 0.61-0.76, P < .0001) and better 1-year response rates (partial response or better was 59% on MPT and 37% on MP). Although the trials differed in terms of patient baseline characteristics and thalidomide regimens, there was no evidence that treatment affected OS differently according to levels of the prognostic factors. We conclude that thalidomide added to MP improves OS and PFS in previously untreated elderly patients with multiple myeloma, extending the median survival time by on average 20%.