Generic Health-Related Quality of Life Utility Measure for Preschool Children (Health Utilities Preschool): Design, Development, and Properties.

OBJECTIVES: Health Utilities Preschool (HuPS) was developed to fill the need for a generic preference-based measure (GPM) applicable in early childhood. A GPM has all the properties for higher-order summary measures, such as quality-adjusted life-years, required to inform important policy decisions regarding health and healthcare services. METHODS: Development was in accordance with published standards for a GPM, statistical procedures, and modeling. HuPS incorporates key components of 2 existing measurement systems: Health Status Classification System for Preschool Children and Health Utilities Index Mark 3 (HUI3). The study included a series of 4 measurement surveys: definitional, adaptational, quantificational, and evaluational health-related quality of life (HRQL). HuPS measurements were evaluated for reliability, validity, interpretability, and acceptability. RESULTS: Definitional measurements identified 8 Health Status Classification System for Preschool Children attributes in common with HUI3 (vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain and discomfort), making the HUI3 scoring equation commensurate with HuPS health states. Adaptational measurements informed the content of attribute-level descriptions (n = 35). Quantificational measurements determined level scoring coefficients. HRQL scoring inter-rater reliability (intraclass correlation coefficient = 0.79) was excellent. Continuity of HRQL scoring with HUI3 was reliable (intraclass correlation coefficient = 0.80, P < .001) and valid (mean absolute difference = 0.016, P = .396). CONCLUSIONS: HuPS is an acceptable, reliable, and valid GPM. HRQL scoring is continuous with HUI3. Continuity expands the applicability of GPM (HUI3) scoring to include subjects as young as 2 years of age. Widespread applications of HuPS would inform important health policy and management decisions as HUI3 does for older subjects.

Canadian French translation and linguistic validation of the health-related quality of life utility measure for pre-school children.

BACKGROUND: There is a need to perform a Canadian French translation and linguistic validation of the health-related quality of life utility measure for pre-school children (HuPS) conceptually equivalent to the original Canadian English version. RESEARCH DESIGN AND METHODS: The translation process consisted of forward and back translations. The linguistic validation was performed with the parents of preschool children during face-to-face cognitive debriefing interviews. The whole process was done in accordance with academic standards and the guidance of the Food and Drug Administration (FDA) for patient-reported outcome instruments. RESULTS: The results of back translations indicated that 89% of the sentences were identical or almost identical to the original English-language wording. The review of the back translations led to a change in 13 sentences out of 91 from the reconciled forward translation, while the linguistic validation process with 13 parents led to 14 additional changes. Preliminary reliability validation results indicate a Cronbach's alpha of 0.73. CONCLUSION: The translation and linguistic testing processes were successful in creating a valid HuPS in Canadian French (HuPS-CF). This translation should be the subject of reliability and validity studies in a wide variety of clinical and general populations before to use in research projects.

Commentary. In Praise of Studies That Use More Than One Generic Preference-Based Measure.

OBJECTIVES AND BACKGROUND: Generic preference-based (GPB) measures of health-related quality of life (HRQL) are widely used as outcome measures in cost-effectiveness and cost-utility analyses (CEA, CUA). Health technology assessment agencies favor GPB measures because they facilitate comparisons among conditions and because the scoring functions for these measures are based on community preferences. However, there is no gold standard HRQL measure, scores generated by GPB measures may differ importantly, and changes in scores may fail to detect important changes in HRQL. Therefore, to enhance the accumulation of empirical evidence on how well GPB measures perform, we advocate that investigators routinely use two (or more) GPB measures in each study. METHODS: We discuss key measurement properties and present examples to illustrate differences in responsiveness for several major GPB measures across a wide variety of health contexts. We highlight the contributions of longitudinal head-to-head studies. RESULTS: There is substantial evidence that the performance of GPB measures varies importantly among diseases and health conditions. Scores are often not interchangeable. There are numerous examples of studies in which one GPB measure was responsive while another was not. CONCLUSIONS: Investigators should use two (or more) GPB measures. Study protocols should designate one measure as the primary outcome measure; the other measure(s) would be used in secondary analyses. As evidence accumulates it will better inform the relative strengths and weaknesses of alternative GPB measures in various clinical conditions. This will facilitate the selection and interpretation of GPB measures in future studies.

What were they thinking when providing preference measurements for generic health states? The evidence for HUI3.

BACKGROUND: Multi-attribute generic preference-based measures of health-related quality of life are used as comprehensive outcome measures. Typically preferences for health states defined by these systems are elicited from a representative sample of the general population. An important element in that elicitation process is the information that respondents were instructed to consider in providing their responses. METHODS: A random sample of community-dwelling respondents in Canada was surveyed in face-to-face interviews. Respondents provided preference scores for selected Health Utilities Index Mark 3 (HUI3) health states. Respondents also answered questions about the most important attributes and the importance of various impacts of the health states in providing their preference scores. RESULTS: Fifty per cent of respondents reported that they focussed on two, and 21% on three, attributes of the eight HUI3 attributes. Each of the eight attributes was identified as important; pain (49%), vision (37%), cognition (34%), emotion (28%), and ambulation (28%) were the most important. The null hypothesis that all of the attributes were equally important was rejected (p < 0.001). With respect to the impacts, 89% of respondents indicated that the ability to take care of oneself was quite or very important; similarly 76% reported the same for impact on family life, 69% for impact on the happiness of others, 61% for the impact on their ability to work, and 42% for the impact on their leisure activities. The null hypothesis that all of the impacts were equally important was rejected (p < 0.001). CONCLUSIONS: In providing preference scores for HUI3 health states, respondents thoughtfully examined the implications of the health states for their ability to live, work, socialize, and function.

Health Status and Health-related Quality of Life Measurement in Pediatric Cancer Clinical Trials: An Examination of the DFCI 00-01 Acute Lymphoblastic Leukemia Protocol.

Health-related quality of life (HRQL) improved progressively during therapy and beyond in children treated for acute lymphoblastic leukemia on the Dana-Farber Cancer Institute (DFCI) 95-01 protocol. This study aimed to validate that trajectory in a successor study (DFCI 00-01) and to compare the HRQL of patients in the 2 studies. Children aged above 5 years were assessed during each phase of treatment (N=4) and 2 years after completion of therapy. Health status and HRQL were measured using Health Utilities Index (HUI) instruments, HUI2 and HUI3. Quality-adjusted life years (QALYs) were calculated and compared with the general population, and patients treated on DFCI 95-01. Over 5 intervals and 758 HUI assessments, mean HRQL increased progressively from remission induction to the time after treatment (P<0.001). During intensification, high-risk patients had lower HRQL than standard-risk patients (P<0.001). During remission induction, patients on DFCI 95-01 had lower HRQL than patients on DFCI 00-01. Patients on DFCI 00-01 had ~0.2 and 0.3 fewer QALYs than controls, measured by HUI2 and HUI3, respectively. QALYs for DFCI 00-01 patients during treatment were similar to those for DFCI 95-01 patients. The trajectory of improvement in HRQL during the treatment of acute lymphoblastic leukemia in children was confirmed.

Health-related Quality of Life in Long-term Survivors of Brain Tumors in Childhood and Adolescence: A Serial Study Spanning a Decade.

Survivors of brain tumors in childhood experience adverse sequelae that are greater in prevalence and severity than those encountered by survivors of all other forms of cancer in early life, reflected in a burden of morbidity by instruments measuring health-related quality of life (HRQL). However, there are few studies of the change in HRQL over time in such populations. Patients who were above 5 years of age, at least 2 years from completion of therapy, and able to communicate in English were eligible for study of HRQL by the Health Utilities Index HUI2 and HUI3 at study entry, and again 5 and 10 years later. An initial cohort of 40 patients was reduced to 37 and 25 at the second and third time points, respectively, although only 1 death occurred during the study. HRQL showed a progressive decline over the decade, reaching conventional levels of clinical significance for the sizes of the changes. Median scores for HUI2 were 0.93, 0.90, and 0.88; and for HUI3 were 0.88, 0.85, and 0.77 at baseline, 5, and 10 years, respectively. The serial decline in HRQL demands further examination and an exploration of potential targets for therapeutic intervention.

Exploration of Morbidity in a Serial Study of Long-Term Brain Tumor Survivors: A Focus on Pain.

PURPOSE: Children surviving brain tumors are frequently identified as having substantially decreased health-related quality of life (HRQL) in cross-sectional studies. This study explored the HRQL of a cohort of such survivors, who were recruited as adolescents and followed for a decade, in order to determine the trajectory of their morbidities. METHOD: Children diagnosed between January 1, 1985, and December 31, 1998, more than 2 years from diagnosis (N = 40), were recruited in 2000/2001 (T1) aged 16.74 ± 4.23 years. Health Utilities Index questionnaires (HUI2/3) were completed in 2000/2001 and again at 5 years (T2) and 10 years (T3), with 37 and 25 participants then aged 21.54 ± 4.29 and 27.97 ± 4.07 years, respectively. In addition to study subjects, parental proxies completed questionnaires at T1 and T2, while study subjects selected proxies at T3. Single attributes (domains/dimensions) of HRQL and details of pain were analyzed. RESULTS: Cognition was the attribute compromised most often (T1 = 66.7% of participants, T2 = 62.2%, T3 = 60.0%). Pain was also reported frequently (T1 = 35%, T2 = 25%, T3 = 52%), and at T3 correlated moderately with HUI2 sensation (0.77) and HUI3 vision (0.44), speech (0.51), and ambulation (0.50). The lower median utility score for pain at T3 than at T1/T2 was a clinically important difference. Severe pain was identified in the lower extremities, back, upper extremities, and abdomen. Morbidity was observed also in emotion (worry HUI2 and unhappiness HUI3), sensation, and vision. CONCLUSION: Decreased HRQL in survivors of brain tumors in childhood is multifaceted. Pain is a prominent burden, along with morbidity in cognition, emotion, sensation, and vision. Further studies should explore pain and neurologic deficits, and potential opportunities for therapeutic intervention.

Surveillance and survival among adolescents and young adults with cancer in Ontario, Canada.

Gains in survival rates among adolescents and young adults (AYA) are reported from the USA to be lower than in both younger and older patients. Limiting factors include low accrual to clinical trials related to the type of institutional care. This study aimed to determine the incidence of cancer in the 15-29 age group in Ontario, and the 5-year survival of these cases by disease class, age at diagnosis group and highest level of institutional complexity of care. The primary data source was Cancer Care Ontario (CCO). Diseases were classified according to an AYA-specific system. Age at diagnosis was grouped as 15-19, 20-24 and 25-29 years; and institutional site of care was categorized as pediatric oncology group of Ontario (POGO) centers, regional cancer centers (RCC-tertiary care centers associated with CCO), RCC affiliate and satellite institutions and other institutions having no specialized cancer services. More than 10,000 incident cases were identified during 1990-2001. Carcinomas and lymphomas each accounted for > 20% of the total. Overall 5-year survival rate was 83%; significantly higher for lymphomas at POGO centers and RCC than elsewhere. About 40% of eligible AYA cases were treated at a POGO center and 25% of those were accrued to clinical trials. The low proportion of adolescents referred to pediatric cancer centers may result in a survival disadvantage for this group. All AYA, especially with lymphomas, should be referred to specialized centers. Accrual of AYA to clinical trials must be improved substantially.

Health-related quality of life among children with acute lymphoblastic leukemia.

BACKGROUND: The objective was to quantify the health-related quality of life (HRQL) of children treated for acute lymphoblastic leukemia (ALL) and identify specific disabilities for remediation. PROCEDURE: Two types of subjects were included: ALL patients 5 plus years old in a multi-center clinical trial and general population control groups. Patients were assessed during all four major phases of active treatment and approximately 2 years after treatment. Health status and HRQL were measured using HEALTH UTILITIES INDEX® (HUI®) Mark 2 (HUI2) and Mark 3 (HUI3). HRQL scores were used to calculate quality-adjusted life years (QALYs). Excess disability rates identified attributes for remediation. RESULTS: HUI assessments (n = 749) were collected during the five phases. Mean HRQL increased from induction through the post-treatment phase (P < 0.001). There were no significant demographic or treatment effects on HRQL, except for type of asparaginase during continuation therapy (P = 0.005 for HUI2 and P = 0.007 for HUI3). Differences in mean HRQL scores between patients and controls were important (P < 0.001) during the active treatment phases but not during the post-treatment phase. Relative to controls, patients lost approximately 0.2 QALYs during active treatment. Disability was evident in mobility/ambulation, emotion, self-care and pain, and declined over time. CONCLUSIONS: Patients with ALL experienced important but declining deficits in HRQL during active treatment phases: Equivalent to losing approximately 2 months of life in perfect health. HRQL within the 2-years post-treatment phase was similar to controls. The policy challenge is to develop new treatment protocols producing fewer disabilities in mobility/ambulation, emotion, self-care, and pain without compromising survival.

Translation and cultural adaptation of health utilities index with application to pediatric oncology patients during neutropenia and recovery in Turkey.

BACKGROUND: This is a report on the translation and cultural adaptation from English to Turkish languages of a standard HEALTH UTILITIES INDEX® (HUI®) questionnaire for interviewer-administration and proxy assessment of patients' health status, and its use for assessing 50 consecutive pediatric oncology patients during periods of and subsequent recovery from neutropenia. PROCEDURE: Preparation of the Turkish-language questionnaire was a collaborative effort by physician-researchers in Turkey, senior Health Utilities, Inc. staff with extensive experience in the development and translation of HUI questionnaires, and Turkish-born residents of Canada. Standard HUI questionnaires cover both HUI Mark 2 (HUI2) and HUI Mark 3 (HUI3). RESULTS: The mean improvement in overall health-related quality of life (HRQL) scores between neutropenic and non-neutropenic phases was clinically important according to both HUI2 and HUI3 instruments. Single-attribute utility scores showed clinically important size improvements between phases for HUI2 mobility, emotion, and HUI2 self-care. Significant reductions in disability rates between phases were also detected for pain (HUI2 and HUI3 rate decreases of 30%, P < 0.001) and HUI3 ambulation (rate decline of 14%, P = 0.020). CONCLUSIONS: The study results provide evidence that the Turkish-language questionnaire is acceptable, valid and useful for collecting parental assessments of health-status among young cancer patients in Turkey. Neutropenia was associated with important deficits in overall HRQL and disabilities in ambulation/mobility, emotion, self-care, and pain. Treatment plans should include strategies for addressing emotion and pain problems to improve the HRQL of neutropenic patients.

Effect of preventive primary care outreach on health related quality of life among older adults at risk of functional decline: randomised controlled trial.

OBJECTIVE: To evaluate the impact of a provider initiated primary care outreach intervention compared with usual care among older adults at risk of functional decline. DESIGN: Randomised controlled trial. SETTING: Patients enrolled with 35 family physicians in five primary care networks in Hamilton, Ontario, Canada. PARTICIPANTS: Patients were eligible if they were 75 years of age or older and were not receiving home care services. Of 3166 potentially eligible patients, 2662 (84%) completed the validated postal questionnaire used to determine risk of functional decline. Of 1724 patients who met the risk criteria, 769 (45%) agreed to participate and 719 were randomised. INTERVENTION: The 12 month intervention, provided by experienced home care nurses in 2004-6, consisted of a comprehensive initial assessment using the resident assessment instrument for home care; collaborative care planning with patients, their families, and family physicians; health promotion; and referral to community health and social support services. MAIN OUTCOME MEASURES: Quality adjusted life years (QALYs), use and costs of health and social services, functional status, self rated health, and mortality. RESULTS: The mean difference in QALYs between intervention and control patients during the study period was not statistically significant (0.017, 95% confidence interval -0.022 to 0.056; P=0.388). The mean difference in overall cost of prescription drugs and services between the intervention and control groups was not statistically significant, (-$C165 ( pound107; euro118; $162), 95% confidence interval -$C16 545 to $C16 214; P=0.984). Changes over 12 months in functional status and self rated health were not significantly different between the intervention and control groups. Ten patients died in each group. CONCLUSIONS: The results of this study do not support adoption of this preventive primary care intervention for this target population of high risk older adults. Trial registration Clinical trials NCT00134836.

Community or patient preferences for cost-effectiveness of cardiac rehabilitation: does it matter?

BACKGROUND: Few healthcare economic evaluations, and none in cardiac rehabilitation, report results based on both community and patient preferences for health outcomes. We published the results of a randomized trial of cardiac rehabilitation after myocardial infarction in 1994 in which preferences were measured using both perspectives but only patient preferences were reported. This secondary analysis uses both types of preference measurements. METHODS: We collected community Quality of Well-Being (QWB) and patient Time Trade-off (TTO) preference scores from 188 patients (rehabilitation, n=93; usual care, n=95) on entry into the trial, at 2 months (end of the intervention) and again at 4, 8, and 12 months. Mean preference scores over the 12-month follow-up study period, estimates of quality-adjusted life years (QALYs) gained per patient, incremental cost-effectiveness ratios [costs inflated to 2006 US dollars] and probabilities of the cost-effectiveness of rehabilitation for costs per QALY up to USD100,000 are reported. RESULTS: Mean QWB preference scores were lower (P<0.01) than the corresponding mean TTO preference scores at each assessment point. The 12-month changes in mean QWB and TTO preference scores were large and positive (P<0.001) with rehabilitation patients gaining a mean of 0.011 (95% confidence interval, -0.030 to +0.052) more QWB-derived QALYs, and 0.040 (-0.026, 0.107) more TTO-derived QALYs, per patient than usual care patients. The incremental cost-effectiveness ratio for QWB-derived QALYs was estimated at $60 270/QALY (about euro50 600/QALY) and at $16 580/QALY (about euro13 900/QALY) with TTO-derived QALYs. With a willingness to spend $100 000/QALY, the probability of rehabilitation being cost-effective is 0.58 for QWB-derived QALYs and 0.83 for TTO-derived QALYs. CONCLUSION: This secondary analysis of data from a randomized trial indicates that cardiac rehabilitation is cost-effective from a community perspective and highly cost-effective from the perspective of patients.

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.

Self and proxy-reported health status and health-related quality of life in survivors of childhood cancer in Uruguay.

BACKGROUND: The incidence of cancer in children in Uruguay is similar to that in industrialized societies but the survival rate is half as great. This study assesses another important measure of treatment effectiveness: the health-related quality of life (HRQL) of survivors. METHODS: All new patients diagnosed in a 3-year period were eligible if free of disease for at least 2 years after therapy and at least 7 years of age at the time of study. A sample of convenient subjects for comparison was obtained from schools and clinics for well children. During a 7-month period, Spanish language interviewer-administered questionnaires were used to collect Health Utilities Index data from survivors and the comparison group (self-reports), and from proxies (parents, physicians, and teachers). RESULTS: Of 113 eligible survivors, 95 (84%) participated together with 96 "control" subjects. Control subjects have a higher mean HRQL utility score than survivors (P < 0.001). The mean score for survivors of acute lymphoblastic leukemia (ALL): 0.72 (n = 49) is higher than the score for survivors of brain tumors: 0.60 (n = 20), as expected. Inter-rater agreement is highest between survivors and parents, and lowest between controls and physicians or teachers. CONCLUSIONS: The burden of morbidity in survivors of childhood cancer in Uruguay is considerable and greater than that in a comparative group of healthy children. Survivors of ALL have better HRQL than survivors of brain tumors, mirroring experience elsewhere. The level of inter-rater agreement is related to the degree of familiarity of the pair-members of respondents with each other.

A prospective study of patients undergoing breast reduction surgery: health-related quality of life and clinical outcomes.

BACKGROUND: This study assessed the health-related quality of life experienced by breast reduction patients using four reliable and validated health-related quality-of-life measures. METHODS: Consecutive patients with breast hypertrophy completed the Health Utilities Index Mark 2, the Health Utilities Index Mark 3, and the Breast Reduction Assessment Value and Outcomes instruments (the Short Form 36, the Multidimensional Body-Self Rating Questionnaire Appearance Assessment, and the Breast-Related Symptom Questionnaire) at 1 week and 1 day before surgery and at 1, 6, and 12 months after surgery. RESULTS: For the 52 patients in the study, mean scores for all quality-of-life instruments increased from the preoperative assessments to the postoperative assessments. The mean quality-adjusted life years gained per patient because of the surgery was 0.12 during the 1-year follow-up period. There was a positive relationship (p < 0.001) between breast resection weight and body mass index. However, body mass index and tissue resection weight were not significantly associated with Health Utilities Index Mark 3 change scores (p > 0.05). CONCLUSIONS: Patients who undergo breast reduction experience an important improvement in health-related quality of life according to four established measures. The improvement is most noticeable between 1 day before surgery and 1 month after surgery, after which it stabilizes for up to 1 year. The health-related quality-of-life effect of the surgery translates into an expected lifetime gain of 5.32 quality-adjusted life years, which is equivalent to each patient living an additional 5.32 years in perfect health. The authors conclude that there is no justification for the ongoing restriction or denials of third-party payments based on body mass index.

Commentary on Cox CL, Lensing S, Rai SN et al. Proxy assessment of quality of life in pediatric clinical trials: application of the Health Utilities Index 3. Qual Life Res 2005; 14: 1045-1056.

The paper by Cox et al. offers an important potential for informing designs of future studies. The rates of missing measurements in the study are much greater than those reported by other investigators. This is not surprising because the nurse assessors were restricted explicitly by the study protocol from collecting required information, had little contact with many of the patients, and some had a poor understanding of the measurement system. Standard multi-attribute system questionnaires, such as the one used in the Cox et al. study, have been designed carefully and require assessments of aspects of health that are not always readily observable (e.g. emotional status). There is an abundance of published evidence, from studies conducted around the world, of acceptable measurement properties for these instruments. However, the published evidence also indicates that measurement properties are compromised with the use of proxy assessors who have little day-to-day knowledge of patients. We conclude that the Cox et al. study results provide evidence that multi-attribute system assessments should be elicited from patients themselves or, failing that, from proxy assessors known to be well-informed about the patients' capacity on all relevant attributes.

Health status measurements at diagnosis as predictors of survival among adults with brain tumors.

PURPOSE: The intent of this study was to determine whether baseline measures of functional capacity and performance could be used to predict survival in adults following the diagnosis of brain tumors. PATIENTS AND METHODS: Comprehensive health status and health-related quality of life (HRQL) were measured using the Health Utilities Index (HUI; McMaster University, Hamilton, Canada) system by a self-assessment questionnaire in a survey of 100 consecutive patients. The Karnofsky Performance Score (KPS) and Folstein's Mini-Mental State Examination (MMSE) scores were measured by a physician blinded to the HUI results. The patients were observed for up to 5 years to recorded dates of death. RESULTS: An HUI questionnaire was completed for 93% of the patients and 69% died within 5 years of assessment. The HUI revealed a burden of morbidity and complexity of disability that far exceeded that reported for the general population. KPS and MMSE correlated strongly with each other (r = 0.52; P < .001). A decrease of 0.1 units in HUI Mark 2 (HUI2) self-care single-attribute utility score was associated with an increased hazard of death of 30% (P = .023) for patients with low-grade tumors (n=25). For patients with high-grade tumors (n=56), a 10 unit decrease in the KPS, a 5 unit decrease in MMSE, and a 0.1 decrease in HUI Mark 3 (HUI3) speech and dexterity single-attribute scores were associated with an increased hazard of death of 20% (P = .022), 26% (P = .015), 36% (P = .021), and 18% (P = .035), respectively. CONCLUSION: Scores derived from the measurement of HRQL following diagnosis can predict survival in adults with brain tumors.