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.

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.

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.

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.

Studies comparing Numerical Rating Scales, Verbal Rating Scales, and Visual Analogue Scales for assessment of pain intensity in adults: a systematic literature review.

CONTEXT: The use of unidimensional pain scales such as the Numerical Rating Scale (NRS), Verbal Rating Scale (VRS), or Visual Analogue Scale (VAS) is recommended for assessment of pain intensity (PI). A literature review of studies specifically comparing the NRS, VRS, and/or VAS for unidimensional self-report of PI was performed as part of the work of the European Palliative Care Research Collaborative on pain assessment. OBJECTIVES: To investigate the use and performance of unidimensional pain scales, with specific emphasis on the NRSs. METHODS: A systematic search was performed, including citations through April 2010. All abstracts were evaluated by two persons according to specified criteria. RESULTS: Fifty-four of 239 papers were included. Postoperative PI was most frequently studied; six studies were in cancer. Eight versions of the NRS (NRS-6 to NRS-101) were used in 37 studies; a total of 41 NRSs were tested. Twenty-four different descriptors (15 for the NRSs) were used to anchor the extremes. When compared with the VAS and VRS, NRSs had better compliance in 15 of 19 studies reporting this, and were the recommended tool in 11 studies on the basis of higher compliance rates, better responsiveness and ease of use, and good applicability relative to VAS/VRS. Twenty-nine studies gave no preference. Many studies showed wide distributions of NRS scores within each category of the VRSs. Overall, NRS and VAS scores corresponded, with a few exceptions of systematically higher VAS scores. CONCLUSION: NRSs are applicable for unidimensional assessment of PI in most settings. Whether the variability in anchors and response options directly influences the numerical scores needs to be empirically tested. This will aid in the work toward a consensus-based, standardized measure.

Minimal important differences and response shift in health-related quality of life; a longitudinal study in patients with multiple myeloma.

BACKGROUND: We previously reported that changes of 6-17 percent in the EORTC QLQ-C30 scores are regarded important by patients with multiple myeloma and thus may be considered as Minimal Important Differences (MIDs). However, patients' internal standard of measurement may have changed over time (response shift, RS). In the present work, we evaluated whether myeloma patients experience RS and if this could affect the MID-estimates. METHODS: Between 2006 and 2008, 239 patients with multiple myeloma completed the EORTC QLQ-C30 at baseline (T1) and after three months (T2). At T2, patients were asked if they had noticed any change in the domains pain, fatigue, physical function and global quality of life. They were also asked to give a retrospective judgment of their baseline values on all the four domains. RESULTS: We found clear evidence of RS in myeloma patients. However, there were differences in both magnitude and direction between patients who stated that they improved and those who deteriorated. Deteriorating patients retrospectively reported better health-related quality of life at T1 for the domains pain, fatigue and physical function. In these patients, MIDs adjusted for RS were observed to increase up to 12 percentage points. In contrast, for patients stating that they improved, we only found evidence of statistically significant RS in the domain global quality of life. CONCLUSIONS: MIDs estimated from pre-test/post-test data appeared to be robust against RS in patients reporting improvement over 3-months. This could indicate that RS has a minimal impact on the results in patients who respond to treatment, and that RS may not have an important impact on interpretation of changes reported in clinical trials where an improvement occurs.Although the effect sizes of the RSs were small, RS in deteriorating patients may have an important impact on the interpretation of changes reported in clinical trials.

Differential item functioning (DIF) analyses of health-related quality of life instruments using logistic regression.

BACKGROUND: Differential item functioning (DIF) methods can be used to determine whether different subgroups respond differently to particular items within a health-related quality of life (HRQoL) subscale, after allowing for overall subgroup differences in that scale. This article reviews issues that arise when testing for DIF in HRQoL instruments. We focus on logistic regression methods, which are often used because of their efficiency, simplicity and ease of application. METHODS: A review of logistic regression DIF analyses in HRQoL was undertaken. Methodological articles from other fields and using other DIF methods were also included if considered relevant. RESULTS: There are many competing approaches for the conduct of DIF analyses and many criteria for determining what constitutes significant DIF. DIF in short scales, as commonly found in HRQL instruments, may be more difficult to interpret. Qualitative methods may aid interpretation of such DIF analyses. CONCLUSIONS: A number of methodological choices must be made when applying logistic regression for DIF analyses, and many of these affect the results. We provide recommendations based on reviewing the current evidence. Although the focus is on logistic regression, many of our results should be applicable to DIF analyses in general. There is a need for more empirical and theoretical work in this area.

The practical impact of differential item functioning analyses in a health-related quality of life instrument.

INTRODUCTION: Differential item functioning (DIF) analyses are commonly used to evaluate health-related quality of life (HRQoL) instruments. There is, however, a lack of consensus as to how to assess the practical impact of statistically significant DIF results. METHODS: Using our previously published ordinal logistic regression DIF results for the Fatigue scale of a HRQoL instrument as an example, the practical impact on a particular Norwegian clinical trial was investigated. The results were used to determine the difference in mean Fatigue scores assuming that the same trial was conducted in the UK. The results were then compared with published information on what would be considered a clinically important change in scores. RESULTS: The item with the largest DIF effect resulted in differences between the mean English and Norwegian Fatigue scores that, although small, could be considered clinically important. Sensitivity analyses showed that larger differences were found for shorter scales, and when the proportions in each response category were equal. DISCUSSION: Our scenarios suggest that translation differences in an item can result in small, but clinically important, differences at the scale score level. This is more likely to be problematic for observational studies than for clinical trials, where randomised groups are stratified by centre.

The relationship between overall quality of life and its subdimensions was influenced by culture: analysis of an international database.

OBJECTIVE: To investigate whether geographic and cultural factors influence the relationship between the global health status quality of life (QL) scale score of the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire and seven other subscales representing fatigue, pain, physical, role, emotional, cognitive, and social functioning. STUDY DESIGN AND SETTING: A large international database of QLQ-C30 responses was assembled. A linear regression model was developed predicting the QL scale score and including interactions between geographical/cultural groupings and the seven other scale scores. RESULTS: The pain subscale appeared to have relatively greater influence and fatigue relatively lower influence for those from other European regions compared with respondents from the UK when predicting overall quality of life (QoL). For Scandinavia physical functioning appeared to contribute relatively less. There was evidence of greater emphasis on cognitive functioning for those from South Asia and Latin America compared with the UK, whereas for those from Islamic countries, the role functioning scale appeared to have less influence and physical and social functioning more influence. CONCLUSION: These results provide evidence that different cultural groups may emphasize different aspects of their QoL. This has implications for studies using QoL questionnaires in international comparisons.

Doloplus-2, a valid tool for behavioural pain assessment?

BACKGROUND: The Doloplus-2 is used for behavioural pain assessment in cognitively impaired patients. Little data exists on the psychometric properties of the Doloplus-2. Our objectives were to test the criterion validity and inter-rater reliability of the Doloplus-2, and to explore a design for validations of behavioural pain assessment tools. METHODS: Fifty-one nursing home patients and 22 patients admitted to a geriatric hospital ward were included. All were cognitively impaired and unable to self-report pain. Each patient was examined by an expert in pain evaluation and treatment, who rated the pain on a numerical rating scale. The ratings were based on information from the medical record, reports from nurses and patients (if possible) about pain during the past 24 hours, and a clinical examination. These ratings were used as pain criterion. The Doloplus-2 was administered by the attending nurse. Regression analyses were used to estimate the ability of the Doloplus-2 to explain the expert's ratings. The inter-rater reliability of the Doloplus-2 was evaluated in 16 patients by comparing the ratings of two nurses administrating the Doloplus-2. RESULTS: There was no association between the Doloplus-2 and the expert's pain ratings (R2 = 0.02). There was an association (R2 = 0.54) between the expert's ratings and the Doloplus-2 scores in a subgroup of 16 patients assessed by a geriatric expert nurse (the most experienced Doloplus-2 administrator). The inter-rater reliability between the Doloplus-2 administrators assessed by the intra-class coefficient was 0.77. The pain expert's ratings were compared with ratings of two independent geriatricians in a sub sample of 15, and were found satisfactory (intra-class correlation 0.74). CONCLUSION: It was challenging to conduct such a study in patients with cognitive impairment and the study has several limitations. The results do not support the validity of the Doloplus-2 in its present version and they indicate that it demands specific administration skills.

Implicit self-comparisons against others could bias quality of life assessments.

OBJECTIVES: To explore how patient-reported health-related quality of life (HRQL) and global health status are affected by use of differing personal reference frames. We hypothesized that implicit comparisons against self at an earlier time, against healthy peers, or against ill patients would greatly affect patients' response values. STUDY DESIGN AND SETTING: Patients in a randomized trial for treatment of Paget's disease completed annual HRQL questionnaires. Supplementary questions were appended, asking the patients whether they were aware of having made implicit comparisons. RESULTS: The majority of patients reported considering themselves a year ago (31% at baseline), themselves before becoming ill (23%), or other healthy people (24%), with similar proportions during follow-up. Mean HRQL scores varied substantially according to the declared frame of reference, with differences as big as 19% of the scale score, or a standardized mean effect size of 0.74 standard deviations. CONCLUSION: Reported reference frames were associated with effects of similar magnitude to the differences in HRQL that are regarded as clinically important. This may be of particular concern in trials that randomize patients to management in different settings, such as treatment at home/in hospital, or surgery/chemotherapy and might bias or obscure HRQL differences.

Applying item response theory and computer adaptive testing: the challenges for health outcomes assessment.

OBJECTIVES: We review the papers presented at the NCI/DIA conference, to identify areas of controversy and uncertainty, and to highlight those aspects of item response theory (IRT) and computer adaptive testing (CAT) that require theoretical or empirical research in order to justify their application to patient reported outcomes (PROs). BACKGROUND: IRT and CAT offer exciting potential for the development of a new generation of PRO instruments. However, most of the research into these techniques has been in non-healthcare settings, notably in education. Educational tests are very different from PRO instruments, and consequently problematic issues arise when adapting IRT and CAT to healthcare research. RESULTS: Clinical scales differ appreciably from educational tests, and symptoms have characteristics distinctly different from examination questions. This affects the transferring of IRT technology. Particular areas of concern when applying IRT to PROs include inadequate software, difficulties in selecting models and communicating results, insufficient testing of local independence and other assumptions, and a need of guidelines for estimating sample size requirements. Similar concerns apply to differential item functioning (DIF), which is an important application of IRT. Multidimensional IRT is likely to be advantageous only for closely related PRO dimensions. CONCLUSIONS: Although IRT and CAT provide appreciable potential benefits, there is a need for circumspection. Not all PRO scales are necessarily appropriate targets for this methodology. Traditional psychometric methods, and especially qualitative methods, continue to have an important role alongside IRT. Research should be funded to address the specific concerns that have been identified.

Pain assessment tools: is the content appropriate for use in palliative care?

Inadequate pain assessment prevents optimal treatment in palliative care. The content of pain assessment tools might limit their usefulness for proper pain assessment, but data on the content validity of the tools are scarce. The objective of this study was to examine the content of the existing pain assessment tools, and to evaluate the appropriateness of different dimensions and items for pain assessment in palliative care. A systematic search was performed to find pain assessment tools for patients with advanced cancer who were receiving palliative care. An ad hoc search with broader search criteria supplemented the systematic search. The items of the identified tools were allocated to appropriate dimensions. This was reviewed by an international panel of experts, who also evaluated the relevance of the different dimensions for pain assessment in palliative care. The systematic literature search generated 16 assessment tools while the ad hoc search generated 64. Ten pain dimensions containing 1,011 pain items were identified by the experts. The experts ranked intensity, temporal pattern, treatment and exacerbating/relieving factors, location, and interference with health-related quality of life as the most important dimensions. None of the assessment tools covered these dimensions satisfactorily. Most items were related to interference (231) and intensity (138). Temporal pattern (which includes breakthrough pain), ranked as the second most important dimension, was covered by 29 items only. Many tools include dimensions and items of limited relevance for patients with advanced cancer. This might reduce compliance and threaten the validity of the assessment. New tools should reflect the clinical relevance of different dimensions and be user-friendly.

The development of the EORTC QLQ-C15-PAL: a shortened questionnaire for cancer patients in palliative care.

This study aimed at developing a shortened version of the EORTC QLQ-C30, one of the most widely used health-related quality of life questionnaires in oncology, for palliative care research. The study included interviews with 41 patients and 66 health care professionals in palliative care to determine the appropriateness, relevance and importance of the various domains of the QLQ-C30. Item response theory methods were used to shorten scales. Patients and health care professionals rated pain, physical function, emotional function, fatigue, global health status/quality of life, nausea/vomiting, appetite, dyspnoea, constipation, and sleep as most important. Therefore, these scales/items were retained in the questionnaire. Four scales were shortened without reducing measurement precision. Important dimensions not covered by the questionnaire were identified. The resulting 15-item EORTC QLQ-C15-PAL is a 'core questionnaire' for palliative care. Depending on the research questions, it may be supplemented by additional items, modules or questionnaires.

The Norwegian Doloplus-2, a tool for behavioural pain assessment: translation and pilot-validation in nursing home patients with cognitive impairment.

BACKGROUND: Pain assessment is challenging in cognitively impaired (CI) patients due to inadequate self-report skills and observational ratings are an alternative. The Doloplus-2 is developed for pain assessment in the CI and rates somatic, psychomotor and psychosocial behaviours as indicators of pain. AIMS: To translate the Doloplus-2 into Norwegian, to test the Doloplus-2 with regard to criterion validity and to obtain the administrators' evaluation of the clinical performance of the Doloplus-2. METHODS: Nurses at three nursing homes, in collaboration with two research assistants, administered the Doloplus-2 to 59 patients with dementia. The results were compared against experienced clinicians' pain ratings. Regression analyses were performed to explore each different item's contribution to the total pain score. The administrators also completed a debriefing questionnaire. RESULTS: The instrument was translated according to international guidelines. Regression analyses demonstrate that the Doloplus-2 score accounts for 62% (R2) of the expert score and that the four most informative items could explain 68% of the expert score. Analyses of the different Doloplus-2 items indicate that facial expressions explain most and social life least of the expert's pain ratings. The administrators reported that Doloplus-2 was helpful and easy to administer, but questioned the validity of the psychosocial domain. CONCLUSIONS: The Norwegian Doloplus-2 demonstrates satisfactory criterion validity and clinical value in this pilot study. However, the content of the instrument needs a general re-evaluation, especially with regard to the psychosocial items.

The CARES-SF used for prospective assessment of health-related quality of life after stem cell transplantation.

OBJECTIVE: By employing the Cancer Rehabilitation and Evaluation System short form (CARES-SF) prospectively we wanted to focus on the rehabilitation needs after high-dose chemotherapy (HDC) and stem cell transplantation, in order to identify problems that should be addressed by health-care professionals during the course of disease and treatment. METHODS: The CARES-SF was administered before and at 2, 6 and 12 months post-transplant to 130 cancer patients treated with HDC and allogeneic (SCT) or autologous stem cell transplantation (ASCT). Physical function scale scores were compared with the corresponding scale of the EORTC QLQ-C30. RESULTS: The SCT group reported significantly better physical function than the ASCT group before transplant on both the CARES-SF (p<0.0001) and the EORTC QLQ-C30 (p<0.01). Almost identical mean CARES-SF scores across groups (SCT: 0.7-1.4, ASCT: 0.8-1.3) were found at the subsequent assessments, consistent with the QLQ-C30 data. Correlations between CARES-SF and QLQ-C30 Physical Function Scales ranged from 0.45 to 0.65. The SCT group had better psychosocial subscale scores (mean 0.4 and 0.5 versus ASCT: 0.7 and 0.8, p < 0.01) at the 6 and 12-month assessments, as well as better satisfaction on the marital subscale ( p=0.01) 6 months post-transplant. Few patients requested specific help: 19% at baseline with 'fear of the cancer progressing' and 9% with 'reduction in physical energy' after 6 and 12 months. CONCLUSION: The CARES-SF detected differences across groups of patients as well as within-patient changes over time. The possibility for patients to express their need for professional assistance renders the CARES-SF appropriate after SCT/ASCT. The sexual, marital and medical interaction subscales in particular address specific issues of relevance for follow-up care, compared with more traditional questionnaires assessing health related quality of life (HRQOL).