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.

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 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.

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.

Health-related quality of life in survivors of tumours of the central nervous system in childhood--a preference-based approach to measurement in a cross-sectional study.

There is an evident need to measure the comprehensive burden of morbidity experienced by survivors of brain tumours in childhood. To this end, a questionnaire based on the Health Utilities Index mark 2 (HUI2) and mark 3 (HUI3) systems was completed independently for a cohort of such children by their parents, by a nurse, by physicians and by a selected group of the children themselves. Each of the HUI2 and HUI3 systems consists of a multi-attribute health status classification scheme linked to a preference function which provides utility scores for levels within single attributes (domains of health) and for global health states. All eligible families (n = 44) participated. Even cognitively impaired children of at least 9.5 years of age could complete the questionnaire. The greatest burden of morbidity, occurring in two-thirds of children, was in the attribute of cognition. Surprisingly, almost one-third of children experienced pain. Global health status was lowest in children who underwent radiotherapy before the age of 5 years and the corresponding utility scores were related inversely to the volume irradiated. Children with demonstrable disease had lower scores than those in whom disease was not evident. There was a high level of agreement (intraclass correlation coefficients > 0.5) on formal assessment of inter-rater reliability for global health-related quality of life utility scores. The usefulness of measures of health status and health-related quality of life, in children surviving brain tumours, has been demonstrated by this study.

Applicability of the Health Utilities Index to a population of childhood survivors of central nervous system tumours in the U.K.

This paper describes the application of a multi-attribute, preference-linked health status and health-related quality of life measurement system--the Health Utilities Index (developed in Canada)--to a group of subjects in the U.K. Children who had survived tumours of the central nervous system (n = 30, age 6-16 years) formed the study group. Respondents (children, parents, physicians and physiotherapists) found the activity (completion of a 15-item questionnaire) to be acceptable and not burdensome (it was accomplished easily by all children > or = 10 years of age). Instrumental reliability was established by acceptable intra- and interobserver agreement and construct validity was supported by strong similarities between the results obtained in this study and those reported from a similar group of children in Canada. The greatest burden of morbidity was reported for the attributes of emotion and cognition (each affected in > 50% of the children). Pain was surprisingly prevalent (affected in approximately one-third of children). The finding of a large number of unique health states emphasises the complex morbidity burden experienced by these children who self-reported poorer overall health (as reflected in utility scores) than did the proxy respondents. The information obtained from this study is readily interpretable and clinically useful. The results of this study also illustrate that extreme caution must be exercised in undertaking linguistic modifications to established instruments for, in this instance, these resulted in a loss of the ability to detect the most severe emotional morbidity and reduced the comparability of results between studies. With this provision, the Health Utilities Index is evidently applicable in the U.K. and the original version has been recommended for use in brain tumour studies by the U.K. CCSG (the U.K. Children's Cancer Study Group).

Assessment of health status and health-related quality of life in survivors of Hodgkin's disease in childhood.

Although the great majority of children with Hodgkin's disease survive with modern treatment strategies, the list of late sequelae is long, yet there is no published information on the comprehensive health status and health-related quality of life (HRQL) in this population. In the experience of a single institution, survivors of Hodgkin's disease in childhood were invited to self-report on their health status using a 15-item questionnaire connected to the Health Utilities Index, a series of multi-attribute health status classification systems that, in turn, are linked to preference functions which provide single-attribute and global utility scores for HRQL. The mean global utility score was 0.85 (on a 0 = dead to 1. 0 = perfect health scale), a figure less than that in survivors of acute lymphoblastic leukemia (ALL) but comparable to that in survivors of brain tumors (0.84) or extremely low birthweight (ELBW 0.82). The burden of morbidity is emphasized by the ratio of the numbers of health states per patient:0.67 for survivors of Hodgkin's disease, 0.66 for survivors of brain tumors, 0.39 for survivors of ELBW, 0.47 for survivors of high-risk ALL and 0.28 for survivors of standard-risk ALL. In Hodgkin's disease survivors, the attributes affected most commonly and severely were pain, cognition and emotion. This experience demands exploration of the health status and HRQL in a much larger cohort of such survivors, perhaps in the context of co-operative group studies.

Mutual concurrent validity of the child health questionnaire and the health utilities index: an exploratory analysis using survivors of childhood cancer.

Mutual concurrent validity of 2 generic measures of health-related quality of life (HRQL), the Child Health Questionnaire (CHQ) and the Health Utilities Index Mark 2 (HUI2) and HUI3, was assessed. Data were from 3 centers participating in a Canadian multi-center retrospective cohort study currently in progress to assess psycho-social and physical late effects in children surviving >/=5 years after cancer diagnosis between 1981 and 1990. Exploratory results are from 244 parent reports on HRQL in children <16 years old when studied. Spearman rank-order correlations between sub-scale scores for the CHQ and single-attribute utility scores for the corresponding attribute from the HUI2 and HUI3 were used. As predicted, the correlation between CHQ bodily pain and HUI2 and HUI3 pain was strong, 0.58 and 0.60, respectively, while correlations between CHQ physical functioning and HUI2 mobility and HUI3 ambulation were moderate, both 0.45. Correlations between CHQ mental health and HUI2 and HUI3 emotion were strong, 0.64 and 0.54, respectively, rather than moderate, as predicted. Both the CHQ general health scale and the general health single item were moderately correlated with the HUI2 and HUI3 global utility scores rather than weakly, as predicted (CHQ general health scale and HUI2 and HUI3 global utility were 0.43 and 0.44, respectively; CHQ general health single item and HUI2 and HUI3 global utility were 0. 38 and 0.42, respectively). The CHQ and HUI, which are based on different methodologies (summative Likert scaling and utility analysis, respectively), appear to capture similar constructs in childhood cancer survivors.

Preliminary translation and cultural adaptation of Health Utilities Index questionnaires for application in Argentina.

Quality-of-life assessment is being used increasingly in clinical research. This is true particularly in the case of survivors of cancer in childhood, where improving survival rates have raised concern regarding the long-term effects of medical cure. Health-status assessment and quality-of-life instruments have been developed for the most part in the English language, thus necessitating their translation and cultural adaptation for use in non-English-speaking countries. Our purpose was to develop a set of Spanish-language questionnaires for application with a population of children with cancer in a tertiary-care center in Buenos Aires, Argentina. The Health Utilities Index (HUI), a conceptual framework for assessing health status, was chosen for this study. Three distinct questionnaires, based on the HUI, were used: a self-completed one for health professionals and teachers (15Q) to report assessments of children and 2 interviewer-administered ones, for child survivors (42Q) to report assessments about their own health status and parents (45Q) to report assessments about their children's health status. The original translations and reviews were accomplished with direct oversight by members of the HUI Group, to ensure conceptual equivalence. The instruments were then tested in Buenos Aires by application to staff of the hematology-oncology service, childhood cancer patients and the parents of childhood cancer patients. Several modifications were made based on these tests. We concluded that the translation and cultural adaptation of these instruments was adequate for use with the groups tested in a pilot survey of survivors of childhood cancer in Argentina.

Predictors of health-related quality of life with cardiac rehabilitation after acute myocardial infarction.

BACKGROUND: Health-related quality of life (HRQL) instruments provide valid and responsive outcome measures to assess the impact of disease and the response to interventions. However, they have not been applied widely to studies of rehabilitation after myocardial infarction. PURPOSE: To examine the extent to which baseline sociodemographic and clinical characteristics predict baseline and change in generic and specific HRQL. METHODS: A randomized controlled trial of an 8-week cardiac rehabilitation intervention or usual care, with follow-up for 12 months, in 201 patients with acute myocardial infarction (MI). Multiple regression analysis was used to identify predictors of HRQL. RESULTS: Specific HRQL scores and exercise tolerance improved significantly more in rehabilitation patients than usual care patients by the end of the 8-week intervention. All HRQL measures and exercise tolerance in both groups improved significantly during the 12 month follow-up period but the differences between the groups were trivial. A poor baseline HRQL was the predominant predictor of improved generic and specific HRQL. Furthermore, greater improvement in HRQL consistently was associated with lower levels of cardiovascular risks such as absence of a previous MI or coronary artery bypass surgery, absence of angina, less smoking, and higher exercise tolerance. CONCLUSIONS: Improved generic and specific HRQL was associated with poorer baseline HRQL and less baseline cardiovascular risk. This reinforces the importance of addressing health behavior changes as soon as possible after MI and the usefulness of assessing both generic and specific HRQL in evaluating treatment effectiveness.

Self-reported comprehensive health status of adult brain tumor patients using the Health Utilities Index.

BACKGROUND: The comprehensive health status of adult survivors of brain tumors is largely unexplored. METHODS: Using a multiattribute approach embodied in a 15-item self-assessment questionnaire, the overall burden of morbidity was measured in 50 brain tumor patients who were attending a neurooncology outpatient clinic. The comprehensive health status was accorded utility scores, and comparisons were made with health status measurements of the general population. RESULTS: The questionnaire was completed with ease by 90% of the respondents. Among the respondents, only 10% of the patients did not report some form of morbidity, and 80% reported multiple impairments. The most prevalent impairments occurred in the attributes of sensation, emotion, and cognition (in this predominantly ambulant group); each of these elements was limited in the majority of patients. A surprising finding was the self-report of pain by nearly 50% of the respondents. CONCLUSIONS: In this group of patients, the burden of morbidity and its complexity greatly exceeded that reported for the general population and were inadequately revealed by Karnofsky performance scores. The use of multiattribute health status measurement tools offers numerous advantages and should be employed in the routine clinical management of cancer patients.