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.

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.

Economic evaluation of allogeneic bone marrow transplantation: a rudimentary model to generate estimates for the timely formulation of clinical policy.

PURPOSE: To provide an evidence-based approach to the formulation of clinical policy with respect to allogeneic bone marrow transplantation (BMT) that involves perceived trade offs between two major factors: costs and consequences. The report also highlights key informational deficiencies. PATIENTS AND METHODS: Adults with acute myeloid leukemia (AML) in second complete remission (2CR) and those with acute lymphoblastic leukemia (ALL) in first complete remission (1CR) were assigned to BMT or control groups solely on the availability of a suitable donor. All hospital-borne costs were estimated, based on services used according to manual chart review, in four categories: diagnostic and therapeutic costs, professional fees, drug costs, and ward costs. Incremental costs and incremental life-years were calculated, and the quotient determined a cost per life-year gained by BMT for AML (2CR) and ALL (1CR). RESULTS: The incremental cost (in 1992 Canadian dollars) per life-year gained by BMT (cost-effectiveness) for AML (2CR) was $29,200; and for ALL (1CR) it was minus $29,200. CONCLUSION: For AML (2CR), allogeneic BMT creates better outcomes than standard treatment, but is more costly. For ALL (1CR), both the costs and outcomes are similar for BMT and standard therapy. Quality adjustments made to life-years gained did not change these conclusions.

A comprehensive multiattribute system for classifying the health status of survivors of childhood cancer.

PURPOSE: A multiattribute health status classification system was devised to describe comprehensively the health status of survivors of childhood cancer. METHODS: The system consists of seven attributes: sensation, mobility, emotion, cognition, self-care, pain, and fertility. Three to five levels of functioning are defined for each attribute. Any specific combination of seven attribute levels constitutes a health state. In the first survey, the system was used to classify the health status of 20 children currently undergoing therapy for high-risk acute lymphoblastic leukemia (ALL), Wilms' tumor, or neuroblastoma, and eight who had completed treatment. A second survey consisted of 13 children with brain tumors on active treatment. RESULTS: In general, independent ratings by clinicians were in agreement, and consensus was readily achieved in 1 to 2 minutes per patient. Children on therapy experienced a higher burden of morbidity than those off treatment. Brain tumor patients experienced more morbidity than patients in the first survey. CONCLUSION: The multiattribute system provides a compact but comprehensive tool for long-term follow-up of survivors of childhood cancer. It captures both multiple sequelae and varying levels of severity. By using a mathematical utility function, a single summary score of health-related quality of life may be assigned to each health state. Additional studies to establish reproducibility, validity, responsiveness, and generalizability are indicated.

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).

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.

Economic evaluation of cardiac rehabilitation soon after acute myocardial infarction.

Although there are extensive clinical evaluations of cardiac rehabilitation after acute myocardial infarction (AMI), no full economic evaluation is available. Patients with AMI and mild to moderate anxiety or depression, or both, while still in hospital were randomized to either an 8-week rehabilitation intervention (n = 99) or usual care (n = 102). Comprehensive costs and health-related quality of life, measured with the time trade-off preference score, were obtained in a 12-month trial, and together with survival data derived from published meta-analyses, cost-utility and cost-effectiveness of early cardiac rehabilitation were estimated. The best estimate of the incremental net direct 12-month costs for patients randomized to rehabilitation was $480 (United States, 1991)/patient. During 1-year follow-up, rehabilitation patients had fewer "other rehabilitation visits" (p < 0.0001) and gained 0.052 quality-adjusted life-year more than did the group with usual care. The cost-utility ratio was $9,200/quality-adjusted life-year gained with cardiac rehabilitation during the year of follow-up. This economic evaluation of cardiac rehabilitation does not consider the important distinctions between affordability and worth of alternative health-care services. The data provide evidence that brief cardiac rehabilitation initiated soon after AMI for patients with mild to moderate anxiety or depression, or both, is an efficient use of health-care resources and may be economically justified.

Health-related quality of life during post-induction chemotherapy in children with acute lymphoblastic leukemia in remission.

Using a multi-attribute approach, we and others have reported on the comprehensive health status of survivors of cancer in childhood, after completion of therapy. However, there is a dearth of information about health status and associated health-related quality of life (HRQL) in children and adults with cancer, during the treatment process; a deficit which this study was intended to redress. All children (n=18) receiving 'maintenance' chemotherapy for acute lymphoblastic leukemia (ALL) at a single institution were assessed prospectively through a single cycle of therapy. Patients, family members and health care professionals used global ratings, the health utilities index mark 2 (HUI2) and mark 3 (HUI3) classification systems, and detailed descriptions of temporary states of health, to provide independent assessments of health status at weekly intervals. Utility scores were derived for each comprehensive health state and for single attribute levels of the HUI2 system, and for the temporary health state descriptions. The classification of the subjects into the most appropriate temporary health states was challenging even for older children and some of the parents. The HUI instruments were used much more easily and produced highly comparable information. The most frequently affected attributes were pain, emotion and mobility/ambulation; in that order. The global (p=0.005) and specific morbidity burdens were, as predicted, greatest in the middle of the cycle of chemotherapy, reflecting the toxicity of steroid use. HUI2 global utility scores demonstrated moderate responsiveness with an intra-class correlation coefficient of 0.43. Cyclical administration of therapy, in particular corticosteroids, produces important changes in health status and HRQL in children with ALL. The HUI are valid and responsive systems for quantifying the burden of morbidity during the treatment of cancer in childhood. These are sensitive tools which can be used in a wide array of other circumstances to quantify changes in health status.

A multiattribute approach to health-status measurement and clinical management illustrated by an application to brain-tumors in childhood.

A comprehensive multi-attribute system was devised to assess global morbidity burden. The system was used to obtain qualitative and quantitative measures of health-status for a case series of survivors of brain tumors in childhood. Health-related quality-of-life scores for each global health-state were calculated from a utility function derived from measures of preferences collected during surveys of a random sample of parents of school age children in the general public (n=194). Global multi-attribute health status (MAHS) utility scores revealed a wide range of severity in morbidity burden. We suggest that the assessment of health-related quality-of-life should become an integral part of clinical management.

The monetary costs of childhood cancer to the families of patients.

The medical costs of cancer treatment are well described, but there are few reports of expenses incurred by families of children with malignant disease. The objective of this study was to describe the monetary costs borne by families of patients with childhood cancer and to determine whether these costs represent an important component of the burden of illness. Families completed a prospective diary survey about daily expenses incurred during each sample week of therapy. We also undertook a retrospective, cross-sectional questionnaire survey about expenses, incurred during the entire duration of treatment, associated with major or one-time cost items. Seventy families of children treated for high risk acute lymphoblastic leukemia, 19 families of children treated for Wilms' tumor stages 2-5, and 16 families of children treated for neuroblastoma stages 3 and 4 completed diaries or questionnaires detailing the costs resulting from the diseases and their treatment. The mean total expenses (in 1986 Canadian dollars) incurred by families of childhood cancer patients over the entire course of therapy are $26,070 for acute lymphoblastic leukemia? $20,074 for Wilms' tumour, and $10,376 for neuroblastoma. On-going weekly costs rather than major one-time purchases account for the largest share of expenses. Overall, in spite of universal first dollar coverage for medical care in Canada, family-borne costs during the course of these illnesses are at least one-third of the average family's after-tax income.

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.

Does it matter whom and how you ask? inter- and intra-rater agreement in the Ontario Health Survey.

A large amount of information in the 1990 Ontario Health Survey (OHS) was collected from proxy respondents using questions administered in face-to-face interviews. Can this type of information represent candid self-reported measures of health status? Inter-rater agreement was assessed using Cohen's kappa statistic for responses to questions that were answered both by individuals about themselves and by proxies on their behalf. Intra-rater agreement, assessing the effect of mode of survey administration (in-person interviews versus self-completed written questionnaires) on the responses, was also investigated using the kappa statistic. We conclude that: (1) proxy responses in the OHS for impairments of emotion and pain are not reliable indicators of self-response (kappa < 0.32) because proxy respondents consistently under-report the burden of morbidity; (2) levels of morbidity reported by subjects to interviewer-administered questionnaires may underestimate morbidity, relative to morbidity reported by subjects using self-administered questionnaires completed in privacy. We also hypothesize that the relative magnitudes of inaccuracy introduced by interviewer administration relative to proxy reporting depends on the phenomenon being measured. When assessing pain, mode of administration is quantitatively a more important source of disagreement than type of respondent.

Effectiveness of infection control program in controlling nosocomial Clostridium difficile.

OBJECTIVE: To report the effectiveness of use of comprehensive infection control measures to reduce the incidence of Clostridium difficile (CD) in an acute-care teaching hospital. METHODS: All CD infections were reviewed by the infection control coordinator from 1987 to 1996. The Centers for Disease Control and Prevention's nosocomial infection definition was used. CD-inclusion criteria remained unchanged during the study period. Interventions were started in 1990. INTERVENTIONS: The interventions used were: (1) Isolation policy-revision and enforcement, which included universal precautions policy, (2) educational program-monthly to all health care workers, (3) phenolic disinfectant for environmental cleaning, (4) triclosan (0.03%) soap for handwashing, (5) centralization of sterilization department, (6) cart-washer installation, and (7) aggressive surveillance activity. RESULTS: From 1987 to 1989, before the interventions, a total of 466 CD infections (mean 155 per year) occurred. From 1990 to 1996, after the interventions, 475 infections (mean 67 per year) occurred. Incidence of CD decreased by 60% from 1990 to 1996. CONCLUSION: The sustained decrease of nosocomial CD during the 7-year period demonstrated the effectiveness of aggressive infection control measures that involve multiple disciplines.

Penfluridol, a peroral long-acting neuroleptic, for the maintenance treatment of schizophrenic patients who relapse.

In a multicenter collaborative study, 28 newly readmitted schizophrenic patients, stabilized for one week on short-acting neuroleptic drugs, had their medication abruptly changed to penfluridol given once a week on an outpatient basis. The average dose required for maintenance was approximately 40 mg weekly. Analysis of BPRS evaluations carried out during the 16-week trial revealed a significant linear trend toward further improvement. Social functioning, as measured by the KAS questionnaire in the outpatient period of the trial, also revealed a significant linear trend toward improvement. Significant worsening was not found with any psychometric evaluation. Side effects, when observed, were neither frequent nor severe. Three laboratory and vital sign values showed significant changes: increase in BUN concentrations, decrease in pulse rate, and increase in body weight. The changes in weight and pulse appeared to be within relatively normal ranges, and the increase in BUN concentrations did not appear to be clinically significant. During the first part of a long-term study, penfluridol received a high degree of patient acceptability and is a welcome addition to the maintenance treatment of schizophrenia.

Multi-attribute preference functions. Health Utilities Index.

Multi-attribute utility theory, an extension of conventional utility theory, can be applied to model preference scores for health states defined by multi-attribute health status classification systems. The type of preference independence among the attributes determines the type of preference function required: additive, multiplicative or multilinear. In addition, the type of measurement instrument used determines the type of preference score obtained: value or utility. Multi-attribute utility theory has been applied to 2 recently developed multi-attribute health status classification systems, the Health Utilities Index (HUI) Mark II and Mark III systems. Results are presented for the Mark II system, and ongoing research is described for the Mark III system. The theory is also discussed in the context of other well known multi-attribute systems. The HUI system is an efficient method of determining a general public-based utility score for a specified health outcome or for the health status of an individual. In clinical populations, the scores can be used to provide a single summary measure of health-related quality of life. In cost-utility analyses, the scores can be used as quality weights for calculating quality-adjusted life years. In general populations, the measure can be used as quality weights for determining population health expectancy.

Multi-attribute health status classification systems. Health Utilities Index.

In this article, multi-attribute approaches to the assessment of health status are reviewed with a special focus on 2 recently developed systems, the Health Utilities Index (HUI) Mark II and Mark III systems. The Mark II system consists of 7 attributes: sensation, mobility, emotion, cognition, self-care, pain and fertility. The Mark III system contains 8 attributes: vision, hearing, speech, ambulation, dexterity, emotion, cognition and pain. Each attribute consists of multiple levels of functioning. A combination of levels across the attributes constitutes a health state. The HUI systems are deliberately focused on the fundamental core attributes of health status, and on the capacity of individuals to function with respect to these attributes. Thus, the measure obtained constitutes a pure description of health status, uncontaminated by differential opportunity or preference. Multi-attribute systems provide a compact but comprehensive framework for describing health status for use in population health and programme evaluation studies. An important advantage of such systems is their ability to simultaneously provide detail on an attribute-by-attribute basis and to capture combinations of deficits among attributes. An additional advantage is their compatibility with multi-attribute preference functions, which provide a method for computing a summary health-related quality-of-life score for each health state.

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.

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.