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.

Bleeding disorders, menorrhagia and iron deficiency: impacts on health-related quality of life.

von Willebrand disease (VWD) is a bleeding disorder that occurs in up to 1% of the general population. The great majority of females with VWD experience menorrhagia. The morbidity burden in females with VWD may relate to iron deficiency resulting from menorrhagia. To explore relationships between bleeding disorders, menorrhagia, iron deficiency and the outcomes of health-related quality of life (HRQL) and educational attainment. All subjects with VWD, and females with other bleeding disorders, in the Canadian national registry who were more than 12 years of age were eligible for survey. Survey measures included the HEALTH UTILITIES INDEX(®); abridged Clinical History Assessment Tool; socio-demographic questions and serum ferritin. Statistical analyses included testing differences among groups of means using analysis of variance and of proportions using chi-squared test. Significant size differences in mean HRQL scores were detected between VWD females and both females with other bleeding disorders [diff = (-0.08); P = 0.017] and VWD males [diff = (-0.07); P = 0.039]. Mean HRQL scores differed between females with and without menorrhagia (P < 0.001). Mean HRQL scores were not significantly different between females with and without iron deficiency. Educational attainment was not associated with disease group, menorrhagia status or iron status. Females with VWD have a greater morbidity burden than females in the general population, females with other bleeding disorders and males with VWD. Menorrhagia is associated with low HRQL scores in females with bleeding disorders, including VWD. Further investigation should assess how menorrhagia impacts HRQL in females with bleeding disorders.

Disability and health-related Quality of Life in Long-term Survivors of Cancer in Childhood in Brazil

There is limited experience with patient-reported measurements of health status and health-related quality of life (HRQL) in survivors of cancer in childhood in low-income countries. The purposes of this study were to collect such measurements in Brazil, to test hypotheses about differences among diagnostic groups, and to compare results with those from other countries. Survivors were eligible if diagnosed with cancer in childhood, attending a long-term follow-up clinic, cancer free, literate, and at least 13 years of age. Health status measurements were collected using a Brazilian Portuguese Health Utilities Index questionnaire. Questionnaire responses were converted to scores for morbidity in individual health attributes and for overall HRQL. More than one-third of the 138 consecutive survivors who participated reported some cognitive disability or pain. Approximately one-quarter reported problems with vision, speech, or emotion. Mean HRQL was similar (P>0.05) among countries for survivors of acute lymphoblastic leukemia and Hodgkin disease. The results support the hypotheses that Brazilian survivors of cancer in childhood experience a wide range of disabilities and impaired HRQL, are similar to those in other countries, and should be assessed in long-term follow-up clinics.

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.

Translation and cultural adaptation of Health Utilities Index (HUI) Mark 2 (HUI2) and Mark 3 (HUI3) with application to survivors of childhood cancer in Brazil

There are few publications reporting health-related quality of life (HRQL) in developing nations. Most instruments measuring HRQL have been developed in English-speaking countries. These instruments need to be culturally adapted for use in non-English-speaking countries. The HUI2 and HUI3 are generic, preference-based systems for describing health status and HRQL. Developed in Canada, the systems have been translated into more than a dozen languages and used worldwide in hundreds of studies of clinical and general populations. The Brazilian-Portuguese translation of the HUI systems was supervised by senior HUInc staff having experience with both the HUI systems and translations. The process included two independent forward translations of the multi-attribute health status classification systems and related questionnaires, consensus between translators on a forward translation, back-translation by two independent translators of the forward translation, and review of the back-translations by original developers of the HUI. The final questionnaires were tested by surveying a sample of convenience of 50 patients recruited at the Centro de Tratamento e Pesquisa-Hospital do Cancer in São Paulo, Brazil. Fifty patients were enrolled in the study. No assessor, patient or nurse or physician, reported problems answering the HUI questionnaires. No significant differences were found in mean overall HUI2 or HUI3 utility scores among types of assessors. Variability in scores are similar to those from other studies in Latin America and Canada. Test results provide preliminary evidence that the Brazilian-Portuguese translation is acceptable, understandable, reliable and valid for assessing health-status and HRQL among survivors of cancer in childhood in Brazil

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.

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.

Health status and health-related quality of life in survivors of cancer in childhood in Latin America: a MISPHO feasibility study.

Cancer is an increasing cause of disease-related death in childhood within developing countries, where the great majority of the world's children reside. The improving prospects for survival in such children, and the corresponding challenge of undertaking economic evaluations of related health interventions, provide a stimulus to study the health-status and health-related quality of life in survivors of cancer in childhood in Latin America. Spanish language versions of questionnaires for proxy assessors, based on the Health Utilities Index (HUI), were used to elicit responses from parents and physicians. The HUI is a family of multi-attribute, generic, preference-linked measures of health status and health-related quality of life that are reliable, responsive and valid, and have been used previously in pediatric oncology. Valid responses were received from 178 parents and 144 physicians in 6 centres in 4 countries (Cuba, Honduras, Colombia and Uruguay). For children with acute lymphoblastic leukemia the major morbidity burdens were in the attributes of emotion, cognition and pain. The overall burden of morbidity was greater in children with non-Hodgkin's lymphoma. In survivors of Hodgkin's disease and Wilms' tumor the attributes most affected were emotion and pain. In general, there was considerable agreement between the assessments provided independently by parents and physicians. This study demonstrates the feasibility of conducting such measurements in developing countries, and reveals similarities in health status and health-related quality of life to comparable populations in more privileged societies.

Venous disease treatment and compliance: the nursing role.

This article explores the numerous factors that influence compliance in the management of venous disease. The nurse's/health practitioner's role is highlighted as being pivotal in promoting compliance or non-compliance. The literature suggests there are many components that influence compliance, varying from impersonal relationships, treatment regimes and psychosocial influences. This implies that compliance is a shared responsibility between the healthcare practitioner/nurse and the patient. Holistic assessment incorporating negotiated care plans will provide the foundation of a partnership in care. Nurses have a responsibility to empower the patients with the necessary knowledge and skills to enable them to be an active participant in their own treatment/life regimes. Nurse education is key to effective, tolerable treatments that are acceptable to patients.

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.

Chronic pain in a family of 6 in the context of litigation.

We describe a family of 6 (2 parents and 4 children), evaluated 6 and 8 years after a minor car accident for chronic pain. A near identical complex of multiple physical, constitutional, and psychological symptoms were shared by all family members, all of whom bore the diagnosis of fibromyalgia. The case was brought to court after nearly a decade of symptomatology and extensive use of the health care system. The minor compensation awarded was consumed ultimately by legal fees. Psychosocial/personality issues and iatrogenic and medico-legal contributions in the evolution and resolution of the legal claim are discussed.

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.

Health Utilities Index Mark 3: evidence of construct validity for stroke and arthritis in a population health survey.

BACKGROUND: The Health Utilities Index Mark 3 (HUI3) is a comprehensive, compact health status classification and health state preference system. The HUI3 system has been included in 4 Canadian population health surveys and numerous clinical trials. OBJECTIVES: To evaluate the construct validity of the HUI3 for the measurement of health-related quality of life (HRQL) and attribute-specific morbidity in respondents to the 1990 Ontario Health Survey reported to have arthritis or stroke. The authors assessed (1) whether those with stroke, arthritis, and both conditions had lower HRQL scores than those with neither condition and (2) whether HUI3 detects morbidity in specific health attributes affected by arthritis and stroke. Stroke (but not arthritis) were expected to affect speech and cognition; arthritis (but not stroke) to affect pain; both to affect mobility, dexterity, and emotion; and neither to affect vision and hearing. RESEARCH DESIGN: Linear regression models of HRQL and attribute-specific utilities were estimated as a function of 3 indicator variables of health problem (stroke only, arthritis only, both) and variables included to reduce confounding. RESULTS: Subjects with stroke, arthritis, and both conditions had substantially lower HRQL than those with neither condition. Stroke subjects had greater morbidity in speech and cognition than arthritis subjects; somewhat surprisingly, pain morbidity was only slightly higher among arthritis subjects; neither condition affected vision or hearing. These associations were robust to various model specifications. CONCLUSIONS: The HUI3 system appears valid for measuring health status and HRQL for stroke and arthritis in the context of a noninstitutionalized population health survey.

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).

Differences in preferences for neonatal outcomes among health care professionals, parents, and adolescents.

CONTEXT: In neonatal intensive care, parents make important clinical management decisions in conjunction with health care professionals. Yet little information is available on whether preferences of health care professionals and parents for the resulting health outcomes differ. OBJECTIVE: To measure and compare preferences for selected health states from the perspectives of health care professionals (ie, neonatologists and neonatal nurses), parents of extremely low-birth-weight (ELBW) or normal birth-weight infants, and adolescents who were either ELBW or normal birth-weight infants. DESIGN: Cross-sectional cohort study. SETTING AND PARTICIPANTS: A total of 742 participants were recruited and interviewed between 1993 and 1995, including 100 neonatologists from hospitals throughout Canada; 103 neonatal nurses from 3 regional neonatal intensive care units; 264 adolescents (aged 12-16 years), including 140 who were ELBW infants and 124 sociodemographically matched term controls; and 275 parents of the recruited adolescents. MAIN OUTCOME MEASURE: Preferences (utilities) for 4 to 5 hypothetical health states of children were obtained by direct interviews using the standard gamble method. RESULTS: Overall, neonatologists and nurses had similar preferences for the 5 health states, and a similar proportion rated some health states as worse than death (59% of neonatologists and 68% of nurses; P=.20). Health care professionals rated the health states lower than did parents of ELBW and term infants (P<.001). Overall, 64% of health care professionals and 45% of parents rated 1 or more health states to be worse than death (P<.001). Differences in mean utility scores between health care professionals and parents and adolescent respondents were most pronounced for the 2 most severely disabled health states (P<.001). CONCLUSIONS: When asked to rate the health-related quality of life for the hypothetical conditions of children, health care professionals tend to provide lower utility scores than do adolescents and their parents. These findings have implications for decision making in the neonatal intensive care unit.