Economic evaluation of treatment for acute lymphoblastic leukaemia in childhood.

Berlin-Frankfurt-Munster (BFM) and Dana-Farber Cancer Institute (DFCI) consortia's treatment strategies for acute lymphoblastic leukaemia (ALL) in children are widely used. We compared the health effects and monetary costs of hospital treatments for these two strategies. Parents of children treated at seven centres in Canada, Italy and the USA completed health-related quality of life (HRQL) assessments during four active treatment phases and at 2 years after treatment. Mean HRQL scores were used to calculate quality-adjusted life years (QALYs) for a period of 5 years following diagnosis. Total costs of treatment were determined from variables in administrative databases in a universally accessible and publicly funded healthcare system. Valid HRQL assessments (n = 1200) were collected for 307 BFM and 317 DFCI patients, with costs measured for 66 BFM and 28 DFCI patients. QALYs per patient were <1.0% greater for BFM than DFCI. Median HRQL scores revealed no difference in QALYs. The difference in mean total costs for BFM (US$88 480) and DFCI (US$93 026) was not significant (P = 0.600). This study provides no evidence of superiority for one treatment strategy over the other. Current BFM or DFCI strategies should represent conventional management for the next economic evaluation of treatments for ALL in childhood.

Norms-based assessment of patient-reported outcomes associated with adalimumab monotherapy in patients with ankylosing spondylitis.

OBJECTIVES: To compare the impact of ankylosing spondylitis (AS) on health-related quality of life (HRQL) and of adalimumab on initial and sustained improvement in HRQL for patients with active AS versus the general US population. METHODS: Data from the 5-year ATLAS trial were analysed. HRQL burden of AS and treatment impact on HRQL were assessed by comparing health status and utility scores from ATLAS (Short Form 36 Health Survey [SF-36] and Health Utilities Index Mark 3 [HUI3]) with population norms. RESULTS: Baseline scores for all measures were comparable between adalimumab and placebo. All scores for both groups were significantly worse than general population norms (all p<0.0001). Within- and between-group improvements in SF-36 Physical Component Summary and SF-6D scores from baseline to Weeks 12 and 24 were clinically relevant for patients receiving adalimumab. For patients initially randomised to adalimumab, HRQL scores improved from Weeks 25 to 52 and remained relatively stable through 3 years but remained lower than for the general US population at all time points. CONCLUSIONS: Findings demonstrate a significant burden of AS on HRQL. Treatment with adalimumab significantly improved physical functioning and other measures of HRQL compared with placebo. Clinically relevant improvements in HRQL outcomes over 3 years represent a significant benefit of adalimumab. Because of the advanced AS disease, patient health status remained below that of the general population. Treatment earlier in the course of AS may be needed to restore HRQL to the level of the general population.

Assessment of health-related quality of life in menopause and aging.

There is a great need for the accurate assessment of health-related quality of life (HRQOL) in clinical practice, research, health interventions and health planning. The menopause transition and special issues influencing the health of women as they age can affect quality of life. The assessment of these effects requires a variety of validated instruments to capture their influence in a variety of populations and for a variety of outcomes. This review identifies the important measurement properties of HRQOL instruments, determinants of health status and the currently available measures of HRQOL. Specifically, the reliability, validity and applicability of HRQOL instruments designed for use at the climacteric are individually discussed. It is important to choose validated and appropriate instruments depending on the individual or population being assessed and the relevant HRQOL issues.

Computerized administration of health-related quality of life instruments compared to interviewer administration may reduce sample size requirements in clinical research: a pilot randomized controlled trial among rheumatology patients.

OBJECTIVES: Computerized health-related quality of life (HRQoL) administration may facilitate clinical trials incorporating HRQoL assessment in rheumatology patients by reducing sample size requirements. We tested this hypothesis in a pilot randomized controlled trial. METHODS: Chinese-speaking adult rheumatology outpatients were randomized to computerized (PC) or interviewer (IA) administration of the EQ-5D (utility & VAS), Health Utilities Index (HUI2 & HUI3) and Family Functioning Measure (FFM). We compared measurement variability (i.e., variance) between PC and IA for each instrument before (Levene's test) and after adjusting for the effects of age, gender and education (multivariable modeling) and computed the variance ratio (VR) for PC over IA. RESULTS: In 138 patients (mean age: 48), the mean (SD) time for administration was similar for PC (n = 67) and IA (n = 71) at 17.7 (7.94) versus 17.3 minutes (7.49), respectively. More subjects expressed a preference for PC (n = 21) over IA (n = 13). Mean HRQoL scores were not significantly different for PC versus IA except for higher VAS scores with IA (difference -7.7, 95% CI -14.0 to 1.3, p = 0.018). Variances and adjusted VR were smaller with PC for the EQ-5D (adjusted VR 0.34, 95% CI 0.18 to 0.65), HUI3 (0.49, 0.27 to 0.89) and FFM (0.95, 0.61 to 1.46), but larger for the HUI2 (1.30, 0.67 to 2.55) and VAS (1.05, 0.55 to 2.00). CONCLUSION: The reduced variability in 3 of 5 instruments and good acceptance of computerized HRQoL assessment, if confirmed in larger studies, may lead to smaller sample size requirements, with potential reductions in cost and recruitment time for clinical trials and cohort studies.

Development, reliability and validity of a new measure of overall health for pre-school children.

BACKGROUND: Few comprehensive systems are available for assessing and reporting the overall health of preschool children. OBJECTIVES: (i) To develop a multi-dimension health status classification system (HSCS) to describe pre-school (PS) children 2.5-5 years of age; (ii) to report reliability and validity of the newly developed measure. DESIGN: Existing systems (Health Utilities Index, Mark 2 and 3) were adapted for application to a pre-school population. The new system was tested for acceptability, validity and reliability. PARTICIPANTS: Three cohorts of children and their parents from Canada and Australia were utilized: Cohort 1 (MAC)-101 3-years old very low birthweight (VLBW, <1500 g) and 50 same age term children from Canada; Cohort 2 (AUS)-150 VLBW 3-years old from Australia; Cohort 3 (OMG)-222 3-years old with cerebral palsy (CP) from Ontario. METHODS: Parental intra-rater reliability was evaluated by completion of the HSCS-PS Parent questionnaire (MAC) at the clinic visit and again 14 days later. Health professionals (MAC) completed the HSCS-PS Clinician questionnaire. Percent agreement and Kappa values were used to assess parent-clinician agreement. Concurrent validity was tested in two populations of VLBW children (MAC and AUS) and a reference group of term children (MAC) by exploring the relationships between dimensions of the HSCS-PS and well-recognized norm-referenced measures: the Bayley Scales of Infant Development (BSID-II), the Vineland Adaptive Behavior Scales (VABS) and the Stanford-Binet (SB). Construct validity was tested by comparing ratings on both the HSCS-PS and the Gross Motor Function classification system (GMFCS) using a population of pre-school children with CP. Analyses were done using chi2, ANOVA and correlations with tau-b statistic. RESULTS: The HSCS-PS has 12 dimensions and 3-5 levels per dimension. Response rate for parental intra-rater reliability was 95%, with percent agreement ranging between 86 and 100%. Kappa values for various dimensions ranged from 0.38 to 1.00. Inter-rater reliability between parents and clinicians showed agreement ranging from 72 to 100%. Kappa values ranged from 0.30 to 1.00. CONCURRENT VALIDITY: There was a statistically significant gradient between HSCS-PS Mobility levels and motor scale scores of the BSID-II and VABS. A significant gradient also occurred when comparing HSCS-PS cognition levels to psychometric scores on the BSID-II and SB, as well as HSCS-PS self-care levels compared to VABS Daily Living scores. DISCRIMINATIVE AND CONSTRUCT VALIDITY: Birthweight category was shown to be a significant determinant of proportion of children with multiple HSCS-PS dimensions affected. In addition, HSCS-PS dimension levels were congruent with GMFCS levels where expected: mobility had excellent correlation; self-care, dexterity, speech and cognitive dimensions had moderate correlations. CONCLUSIONS: The HSCS-PS is readily accepted, quick to complete, widely applicable and provides a multi-dimensional description of health status. Preliminary assessments of reliability and validity are promising. The HSCS-PS can discriminate across populations by birthweight and shows strong relationships with standardized psychometric measures in comparable domains. It can pro- vide a summary profile of functional limitations in various populations of pre-school children in a consistent manner across programs and in different settings.

Baseline FACT-G score is a predictor of survival for advanced lung cancer.

UNLABELLED: The objective of this study is to evaluate whether patient-reported baseline health-related quality of life (HRQL) measured by the Functional Assessment of Cancer Therapy-General (FACT-G) instrument is predictive of survival for patients with advanced lung cancer. METHODS: Consecutive patients with advanced lung cancer planning to undergo palliative chemotherapy in the outpatient clinics of a Canadian tertiary care cancer centre were enrolled on study. FACT-G total scores and clinical predictors of survival (age, sex, histology, stage of disease, previous weight loss, presence of liver metastases and performance status) were prospectively collected at baseline. Survival data was subsequently collected retrospectively from the Alberta Cancer Registry. Stratified Cox Proportional Hazards analysis was done examining the influence of baseline total FACT-G scores on survival, controlling for potential clinical confounders. RESULTS: Median survival of the 42 patient cohort was 9.9 months with a 2-year survival of 16.7%. Multivariate analysis indicated that baseline FACT-G total score is significantly associated with survival (p = 0.004). CONCLUSION: Baseline HRQL is a statistically significant predictor of survival for patients with advanced lung cancer. When used along with traditional clinical factors, patient-reported baseline HRQL assessment using the FACT-G provides additional prognostic information to the patient and clinician.

Health status of young children during therapy for advanced neuroblastoma.

BACKGROUND: The purpose of this study was to describe the health status experienced by young children during various phases of therapy for advanced neuroblastoma. METHODS: Nineteen patients aged 2.00-4.99 years at the time of diagnosis of neuroblastoma (stages 3 or 4) who received active therapy between 1996 and 2000 were enrolled on the study. Their parents provided proxy assessments of their health status at a maximum of 10 assessment points during therapy using the Comprehensive Health Status Classification System for Pre-school Children (CHSCS-PS), which assesses level of function on 10 separate health domains. RESULTS: Eighty-six assessment questionnaires were completed. Maximum morbidity was reported immediately following diagnosis and in the 2-3 weeks following bone marrow transplantation. The greatest morbidity was observed in the pain, self-care, mobility, and emotion domains. CONCLUSIONS: In addition to facing a high risk of mortality, young children being treated for advanced neuroblastoma also experience considerable morbidity.

The stability of utility scores: test-retest reliability and the interpretation of utility scores in elective total hip arthroplasty.

PURPOSES: Are utility scores for hypothetical health states stable over time even when the health of the patient changes dramatically? Can investigators who use scores for hypothetical states be confident about the stability of those scores? The first purpose is to assess the stability of standard gamble utility scores for three hypothetical health states describing mild, moderate, and severe osteoarthritis (OA) (test-retest reliability). How should investigators interpret utility scores? The second purpose is to provide evidence on the marker-state approach to assist in interpreting utility scores. BACKGROUND: SG scores for three hypothetical marker states and the patient's current state were obtained at multiple times in a longitudinal study of elective total hip arthroplasty (THA). SG scores for current health increased from a mean of 0.59 pre-surgery to 0.76 post-surgery. METHODS: Test-retest reliability was assessed using the intra-class correlation coefficient (ICC). The effects of time on scores were analysed using an analysis of covariance. RESULTS: At the group level the marker-state scores were stable. Mean scores for mild, moderate, and severe OA were 0.69, 0.61, and 0.41. With respect to test-retest reliability, ICCs varied from 0.49 to 0.62. In general, time did not affect the scores for the three marker states. CONCLUSIONS: Group-level standard gamble scores are stable. At the individual level scores for hypothetical health states are somewhat stable over time. The marker states assist in interpretation indicating that, on average, THA converted moderate OA to better than mild.

Inter-observer agreement of a comprehensive health status classification system for pre-school children among patients with Wilms' tumor or advanced neuroblastoma.

We assessed inter-observer agreement on a new comprehensive health status classification system for preschool children (CHSCS-PS). Prospective assessments of children aged 2-4.9 years at the time of diagnosis of neuroblastoma (stages 3-4, excluding 4S) or Wilms' tumor (stages II-V) were collected independently from a parent and nurse by self-report during therapy. Responses were used to determine functional status on 10 health domains, as well as an overall disability score. Inter-observer agreement was evaluated by a kappa statistic for agreement about levels within individual domains, and by an intraclass correlation coefficient (ICC) for agreement of overall disability scores. Twenty-four parent/nurse pairs of assessments were collected. Agreement was almost perfect for mobility and self-care, substantial for emotion and pain, and slight for speech. There was high percent agreement for vision, hearing, dexterity, learning and remembering, and thinking and problem solving, but insufficient variability in responses to calculate a kappa statistic. The ICC for overall disability scores between observers was 0.86, indicating strong agreement. Given the need for, and paucity of, instruments for the measurement of health-related quality of life in very young children, these results strongly support further evaluation of the CHSCS-PS.

The Health Utilities Index (HUI) system for assessing health-related quality of life in clinical studies.

This paper reviews the Health Utilities Index (HUI) systems as means to describe health status and obtain utility scores reflecting health-related quality of life (HRQoL). The HUI Mark 2 (HUI2) and Mark 3 (HUI3) classification and scoring systems are described. The methods used to estimate multiattribute utility functions for HUI2 and HUI3 are reviewed. The use of HUI in clinical studies for a wide variety of conditions in a large number of countries is illustrated. HUI provides a comprehensive description of the health status of subjects in clinical studies. HUI has been shown to be a reliable, responsive and valid measure in a wide variety of clinical studies. Utility scores provide an overall assessment of the HRQoL of patients. Utility scores are also useful in cost-utility analyses and related studies. General population norm data are available. The widespread use of HUI facilitates the interpretation of results and permits comparisons. HUI is a useful tool for assessing health status and HRQoL in clinical studies.

Visual analog scales: do they have a role in the measurement of preferences for health states?

Visual analog scales (VASs) have long been used as a method of measuring preferences for health outcomes. They are easy and inexpensive to implement, can be administered quickly, and lend themselves to self-completion. Over time, however, disturbing questions have emerged concerning the validity of the VAS approach. This article reviews briefly the history, theory, practice, problems, and advantages of VASs; presents some suggestions to improve the validity of VASs; and recommends a limited but useful role for VASs in the process of measuring preferences for health states.

The role of permanent income and family structure in the determination of child health in Canada.

We use data from the Ontario Child Health Study (OCHS) to provide the first Canadian estimates of how the empirical association between child health and both low-income and family status (lone-mother versus two-parent) changes when we re-estimate the model with pooled data. Two waves of data provide a better indication of the family's long-run level of economic resources than does one wave. Our measures of health status include categorical indicators and the health utility score derived from the Health Utilities Index Mark 2 (HUI2) system. Consistent with findings from other countries, we find that most outcomes are more strongly related to low-average income (in 1982 and 1986) than to low-current income in either year. Unlike some previous research, we find the quantitative impact of low-income on child health to be modest to large. Lone-mother status is negatively associated with most outcomes, but the lone-mother coefficients did not change significantly when we switched from low-current income to low-average income. This implies that the lone-mother coefficient in single cross-sections is not just a proxy for low-permanent income.

Decision analysis of prenatal testing for chromosomal disorders: what do the preferences of pregnant women tell us?

Current guidelines recommend offering invasive testing for chromosomal disorders only to women who are aged 35 or older, or who are at similarly elevated risk (as determined by maternal serum and/or ultrasonographic screening). We conducted a decision analysis, using preference scores obtained from pregnant women, to determine whether current guidelines maximize the health-related quality of life of these women. If only miscarriage and chromosomal abnormalities are considered, the expected value of testing exceeds that of not testing for women 30 years of age or older. However, if a comprehensive range of relevant testing outcomes is considered, testing offers a higher expected value than not testing, regardless of age. Furthermore, patient preferences for specific testing outcomes play a much more substantial role in determining the course of action with the highest expected value than does the probability of any of the possible testing outcomes. The current age- and risk-based guideline for prenatal diagnosis does not maximize expected value and fails to appropriately consider individual patient preferences. For counseling purposes, how an individual values the presence and timing of fetal chromosomal information should be carefully understood.

A comparison of HUI2 and HUI3 utility scores in Alzheimer's disease.

PURPOSE: The Health Utilities Index (HUI) is a generic, multiattribute, preference-based health-status classification system. The HUI Mark 3 (HUI3) differs from the earlier HUI2 by modifying attributes and allowing more flexibility for capturing high levels of impairment. The authors compared HUI2 and HUI3 scores of patients with Alzheimer's disease (AD) and caregivers, and contrasted results of a cost-effectiveness analysis of new drugs for AD using the two systems. METHODS: In a cross-sectional study of 679 AD patient/caregiver pairs, stratified by patient's disease stage (questionable/mild/moderate/severe/profound/terminal) and setting (community/assisted living/nursing home), caregivers completed the combined HUI2/HUI3 questionnaire as proxy respondents for patients and for themselves. RESULTS: Mean (SD) global utility scores for patients were lower on the HUI3 (0.22[0.26]) than on the HUI2 (0.53 [0.21]). Patient HUI3 utility scores ranged from 0.47(0.24) for questionable AD to -0.23 (0.08) for terminal AD, compared with a range of 0.73 (0.15) to 0.14 (0.07) for the HUI2. Among the 203 patients in the severe, profound, and terminal stages, 96 (48%) had negative global HUI3 utility scores, while none had a negative HUI2 score. The utility scores for caregivers were similar on the HUI3 (0.87 [0.14]) and HUI2 (0.87 [0.11]). Cost-effectiveness analysis of a new medication to treat AD showed somewhat more favorable results using the HUI3. CONCLUSIONS: The HUI2 and HUI3 discriminate well across AD stages. Compared with the HUI2, the HUI3 yields lower global utility scores for patients with AD, and more scores for states judged worse than dead. The HUI3 may yield substantially different results from the HUI2, particularly for persons who have serious cognitive impairments such as AD.

Health-related quality of life in survivors of Wilms' tumor and advanced neuroblastoma: aA cross-sectional study.

PURPOSE: In pediatric oncology, Wilms' tumor and advanced neuroblastoma represent opposite ends of the spectra of survival probability and therapeutic intensity. Consequently, it was envisaged that survivors of Wilms' tumor would enjoy better health status and health-related quality of life (HRQL) than survivors of advanced neuroblastoma. PATIENTS AND METHODS: Health status questionnaires were sent to the parents of all eligible children and to the children themselves if they were > or = 8 years of age. Responses were received from 84% of 93 eligible families. Responses were converted by established algorithms into levels of two multiattribute health status classification systems known as Health Utilities Index Mark 2 and Mark 3. These systems are linked to measures of preference, in the form of multiattribute utility functions, which provide scores of morbidity for single-attribute levels and of global HRQL for comprehensive health states. RESULTS: A greater burden of morbidity was identified in the survivors of advanced neuroblastoma than in survivors of Wilms' tumor based on the assessments of the parents of these children. In particular, survivors of advanced neuroblastoma exhibited deficits in hearing and speech. It is possible that this morbidity burden reflects the prevalent use of platinum compounds (causing ototoxicity) in this group. Within parent-child dyads there was a high level of percentage agreement on responses in all attributes except cognition. CONCLUSION: Extension of this study to a larger sample size of patients will provide clarification of these observations.

German cross-cultural adaptation of the Health Utilities Index and its application to a sample of childhood cancer survivors.

UNLABELLED: Steady progress in developing effective treatments for childhood cancer and other severe pediatric diseases has established the need to consider the nature and frequency of late physical and psychological effects. The Health Utilities Index Mark 2 and Mark 3 (HUI2/3) systems were developed by Feeny, Furlong, Torrance et al. in Canada. These systems are generic multi-attribute measures of a person's health status and health-related quality of life. The first German version of the Canadian HUI2/3 questionnaire was created in our clinic, following recommended guidelines for cross-cultural adaptation of health-related quality of life measures. The usefulness of the resultant version was investigated using a sample of 142 patients who presented to our oncological outpatients' department for a routine health care visit after completion of treatment. The 15 items of the HUI2/3-questionnaire were answered independently by three groups of assessors--nurses, physicians, and parents or patients. Two additional questions covered ratings of the severity of treatment effects and the specification of these effects. The questionnaire was both easy to use and acceptable to the assessors. Percentage agreement between observers about levels for individual attributes ranged from 56% to 100%, with the lowest agreement on the subjective attributes of emotion, pain and cognition. These results are in accordance with previous studies using the original instrument. HUI2 global utility scores were significantly related to ratings of treatment sequelae, giving support to the discriminant validity of the measure. CONCLUSION: The German version of HUI2/3 is a useful instrument with generally high inter-observer agreement and good suitability for outcome measurement in childhood cancer patients. Further research is needed to assess the usefulness of the instrument in other clinical populations and its sensitivity in longitudinal studies.

Parental perspectives of the health status and health-related quality of life of teen-aged children who were extremely low birth weight and term controls.

OBJECTIVES: To compare the health status and health-related quality of life of teen-aged children who were extremely low birth weight (ELBW) with matched controls from the perspective of their parents. STUDY DESIGN: Geographically defined cohort; longitudinal follow-up; cross-sectional interviews. PARTICIPANTS: parents of 149/169 (88%) ELBW children between 12 and 16 years of age (including 41 children with neurosensory impairments) and 126/145 (87%) parents of term controls. Health status of the teenagers was classified according to the 6 attributes of the Health Utilities Index Mark 2, based on information obtained during parent interviews. Parents were asked to imagine themselves living in their own child's health state and 4 preselected hypothetical health states when providing directly measured standard gamble utility scores. RESULTS: Parents of ELBW children reported a higher frequency and more complex functional limitations than parents of controls for their own children's health status. Also, the mean utilities were lower (ELBW =.91 vs controls =. 97) and the variability in their scores was greater. There were no differences in the valuation of the hypothetical health states provided by parents of ELBW and control children. CONCLUSIONS: ELBW children were reported to have a greater burden of disability than were control children based on parental descriptions. Nonetheless, parents of ELBW children, on average, rated the health-related quality of life of their children fairly high. Thus, differences in reported functional status are not necessarily associated with lower utility scores.