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John E Brazier

Publications and source records attributed to John E Brazier.

17 recordsLinked to original sources

Modelling covariates for the SF-6D standard gamble health state preference data using a nonparametric Bayesian method.

It has long been recognised that respondent characteristics can impact on the values they give to health states. This paper reports on the findings from applying a non-parametric approach to estimate the covariates in a model of SF-6D health state values using Bayesian methods. The data set is the UK SF-6D valuation study, where a sample of 249 states defined by the SF-6D (a derivate of the SF-36) was valued by a sample of the UK general population using standard gamble. Advantages of the nonparametric model are that it can be used to predict scores in populations with different distributions of characteristics and that it allows for an impact to vary by health state (whilst ensuring that full health passes through unity). The results suggest an important age effect, with sex, class, education, employment and physical functioning probably having some effect, but the remaining covariates having no discernable effect. Adjusting for covariates in the UK sample made little difference to mean health state values. The paper discusses the implications of these results for policy.

Adult↗

Modelling SF-6D health state preference data using a nonparametric Bayesian method.

This paper reports on the findings from applying a new approach to modelling health state valuation data. The approach applies a nonparametric model to estimate SF-6D health state utility values using Bayesian methods. The data set is the UK SF-6D valuation study where a sample of 249 states defined by the SF-6D (a derivative of the SF-36) was valued by a representative sample of the UK general population using standard gamble. The paper presents the results from applying the nonparametric model and comparing it to the original model estimated using a conventional parametric random effects model. The two models are compared theoretically and in terms of empirical performance. The paper discusses the implications of these results for future applications of the SF-6D and further work in this field.

Bayes Theorem↗

Impact of discussion on preferences elicited in a group setting.

BACKGROUND: The completeness of preferences is assumed as one of the axioms of expected utility theory but has been subject to little empirical study. METHODS: Fifteen non-health professionals was recruited and familiarised with the standard gamble technique. The group then met five times over six months and preferences were elicited independently on 41 scenarios. After individual valuation, the group discussed the scenarios, following which preferences could be changed. Changes made were described and summary measures (mean and median) before and after discussion compared using paired t test and Wilcoxon Signed Rank Test. Semi-structured telephone interviews were carried out to explore attitudes to discussing preferences. These were transcribed, read by two investigators and emergent themes described. RESULTS: Sixteen changes (3.6%) were made to preferences by seven (47%) of the fifteen members. The difference between individual preference values before and after discussion ranged from -0.025 to 0.45. The average effect on the group mean was 0.0053. No differences before and after discussion were statistically significant. The group valued discussion highly and suggested it brought four main benefits: reassurance; improved procedural performance; increased group cohesion; satisfying curiosity. CONCLUSION: The hypothesis that preferences are incomplete cannot be rejected for a proportion of respondents. However, brief discussion did not result in substantial number of changes to preferences and these did not have significant impact on summary values for the group, suggesting that incompleteness, if present, may not have an important effect on cost-utility analyses.

Aged↗

Mapping between Visual Analogue Scale and Standard Gamble data; results from the UK Health Utilities Index 2 valuation survey.

We examine the relationship between Visual Analogue Scale (VAS) and Standard Gamble (SG) assumed in the development of the multiplicative multi-attribute utility functions (M-MAUFs) for the Health Utilities Index (HUI) Mark 2 and Mark 3, using data from a UK valuation study of the HUI2. A range of functional forms are considered, and are compared on the basis of their explanatory power and predictive ability.A restricted cubic function fits the data better than a power curve with a mean absolute error (MAE) of 0.025 and root mean square error (RMSE) of 0.029 compared to a MAE of 0.135 and RMSE of 0.135 for the power curve. The use of a cubic mapping function instead of a power function leads to different predicted health state values. We question the reliance on the assumption of a power curve relationship between VAS and SG data, in the Health Utilities Index valuation framework. Our results demonstrate that further work is required to examine the appropriateness of the published M-MAUFs for the Health Utilities Indices.

Data Collection↗

Estimating a preference-based index for a menopause specific health quality of life questionnaire.

BACKGROUND: The aim of the study was to develop a menopause-specific, preference-based health-related quality-of-life (HRQoL) index reflecting both menopausal symptoms and potential side-effects of Hormone Replacement Therapy (HRT). METHODS: The study had three phases: the development of a health state classification, a prospective valuation survey and the estimation of a model to interpolate HRQoL indices for all remaining health states as defined by the classification. A menopausal health state classification was developed with seven dimensions: hot flushes, aching joints/muscles, anxious/frightened feelings, breast tenderness, bleeding, vaginal dryness and undesirable androgenic signs. Each dimension contains between three and five levels and defines a total of 6,075 health states. A sample of 96 health states was selected for the valuation survey. These states were valued by a sample of 229 women aged 45 to 60, randomly selected from 6 general practice lists in Sheffield, UK. Respondents were asked to complete a time trade-off (TTO) task for nine health states, resulting in an average of 16.5 values for each health state. RESULTS: Mean health states valued range from 0.48 to 0.98 (where 1.0 is full health and zero is for states regarded as equivalent to death). Symptoms, as described by the classification system, can be rank-ordered in terms of their impact (from high to low) on menopausal HRQoL as follows: aching joints and muscles, bleeding, breast tenderness, anxious or frightened feelings, vaginal dryness, androgenic signs. Hot flushes did not significantly contribute to model fit. The preferred model produced a mean absolute error of 0.053, but suffered from bias at both ends of the scale. CONCLUSION: This article presents an attempt to directly value a condition specific health state classification. The overall fit was disappointing, but the results demonstrate that menopausal symptoms are perceived by patients to have a significant impact on utility. The overall effect is modest compared to the more generic health state descriptions such as the EQ-5D. The resultant algorithm generates a preference-based index that can be used economic evaluation and that reflects the impact of this condition.

Female↗

Are indirect utility measures reliable and responsive in rheumatoid arthritis patients?

BACKGROUND: Preference-based, generic measures are increasingly being used to measure quality of life and as sources for quality weights in the estimation of Quality Adjusted Life Years (QALYs) in rheumatoid arthritis (RA). However, among the most commonly used instruments (the Health Utilities Index 2 and 3 [HUI2 and HUI3], the EuroQoL-5D [EQ-5D], and the Short Form-6D [SF-6D], there has been little comparative research. Therefore, we examined the reliability and responsiveness of these measures and the Rheumatoid Arthritis Quality of Life (RAQoL) and the Health Assessment Questionnaire (HAQ) in a sample of RA patients. MAJOR FINDINGS: Test-retest reliability was acceptable for all of the instruments with the exception of the EQ-5D. Using two external criteria to define change (a patient transition question and categories of the patient global assessment of disease activity VAS), the RAQoL was the most responsive of the instruments. For the indirect utility instruments, the HUI3 and the SF-6D were the most responsive for measuring positive change. On average, for patients whose RA improved, the absolute change was highest for the HUI3. CONCLUSIONS: The HUI3 and the SF-6D appear to be the most responsive of the preference-based instruments in RA. However, differences in the magnitude of the absolute change scores have important implications for cost-effectiveness analyses.

Arthritis, Rheumatoid↗

Comparison of the minimally important difference for two health state utility measures: EQ-5D and SF-6D.

BACKGROUND: The SF-6D and EQ-5D are both preference-based measures of health. Empirical work is required to determine what the smallest change is in utility scores that can be regarded as important and whether this change in utility value is constant across measures and conditions. OBJECTIVES: To use distribution and anchor-based methods to determine and compare the minimally important difference (MID) for the SF-6D and EQ-5D for various datasets. METHODS: The SF-6D is scored on a 0.29-1.00 scale and the EQ-5D on a -0.59-1.00 scale, with a score of 1.00 on both, indicating 'full health'. Patients were followed for a period of time, then asked, using question 2 of the SF-36 as our anchor, if their general health is much better (5), somewhat better (4), stayed the same (3), somewhat worse (2) or much worse (1) compared to the last time they were assessed. We considered patients whose global rating score was 4 or 2 as having experienced some change equivalent to the MID. This paper describes and compares the MID and standardised response mean (SRM) for the SF-6D and EQ-5D from eight longitudinal studies in 11 patient groups that used both instruments. RESULTS: From the 11 reviewed studies, the MID for the SF-6D ranged from 0.011 to 0.097, mean 0.041. The corresponding SRMs ranged from 0.12 to 0.87, mean 0.39 and were mainly in the 'small to moderate' range using Cohen's criteria, supporting the MID results. The mean MID for the EQ-5D was 0.074 (range -0.011-0.140) and the SRMs ranged from -0.05 to 0.43, mean 0.24. The mean MID for the EQ-SD was almost double that of the mean MID for the SF-6D. CONCLUSIONS: There is evidence that the MID for these two utility measures are not equal and differ in absolute values. The EQ-5D scale has approximately twice the range of the SF-6D scale. Therefore, the estimates of the MID for each scale appear to be proportionally equivalent in the context of the range of utility scores for each scale. Further empirical work is required to see whether or not this holds true for other utility measures, patient groups and populations.

Attitude to Health↗

A comparison of generic, indirect utility measures (the HUI2, HUI3, SF-6D, and the EQ-5D) and disease-specific instruments (the RAQoL and the HAQ) in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a common, chronic disease where health-related quality of life (HRQL) is one of the main goals of therapy. As such, instruments used to measure HRQL in RA must be able to discriminate across RA severity. The two basic categories of instruments used to measure HRQL are generic instruments and disease-specific instruments. Generic instruments can be further subdivided into preference-based measures which yield both single and multi-attribute utility values anchored at zero (death) and 1.00 (perfect health) as a measure of HRQL. The scores from these types of instruments can be integrated into cost-utility analyses as the weightings for quality adjusted life years. We assessed the construct validity of utility scores from four generic preference-based measures (the Health Utilities Index 2 and 3 (HUI2, HUI3), the EuroQol 5D (EQ-5D), and the Short Form 6-D (SF-6D) and disease specific measures (the Rheumatoid Arthritis Quality of Life Questionnaire (RAQoL) and the Health Assessment Questionnaire (HAQ)) in a sample of 313 RA patients in British Columbia, Canada. We also estimated the minimally important differences (MID) for each of the measures. Generally, as anticipated, the disease-specific measures were better able to discriminate across groups with higher RA severity; however, utility scores from each of the scales also appeared to discriminate well across RA severity categories. The MID values agreed with those previously reported in the literature for the HUI2, SF-6D and the HAQ and provided new information for the HUI3, EQ-5D and the RAQoL. We conclude that the all of the preference-based utility measures that were evaluated appear to adequately discriminate across levels of RA severity.

Adult↗

Utility scores for the Health Utilities Index Mark 2: an empirical assessment of alternative mapping functions.

INTRODUCTION: The Health Utilities Index is one of the most widely used generic health status classification systems. The valuation algorithm rests upon a power transformation between visual analog scale (VAS) and standard gamble (SG) data. This transformation has been the subject of much debate. To date, the literature has concentrated upon the mapping functions themselves. We examine whether alternative mapping functions produce more accurate utility predictions. METHODS: We undertook valuation interviews with 201 members of the UK general population, following the methods of the original Health Utilities Index-2 valuation survey. We estimated a cubic and a power mapping function using the mean VAS and SG data from the survey and calculated 2 alternative Multiplicative Multi Attribute Utility Functions (MAUFs). Using a validation sample, we assessed the predictive precision of the models in terms of accuracy (root mean square error and mean absolute error); clinical importance of the prediction error (% states with prediction error greater than 0.03); bias (t test); and whether the prediction error was related to the health state severity (Ljung Box Q statistic). RESULTS: The power MAUF was an extremely poor predictive model, mean absolute error = 0.18, root mean square error = 0.206. The predictions were biased (t = -12.92). The errors were not related to the severity of the health state, (Liung Box = 10.87). The Cubic MAUF was a better predictive model than the Power MAUF (mean absolute error = 0.084, root mean square error = 0.101). The Cubic MAUF also produced biased predictions (t = -3.57). The prediction errors were not related to the severity of the health state (Liung Box = 5.242). DISCUSSION: The Power MAUF is considerably worse than the Cubic MAUF. Our results suggest that the problems with the power function can translate into significant problems with predictive performance of the MAUF.

Activities of Daily Living↗

The impact of age-related macular degeneration on health status utility values.

PURPOSE: To estimate health status utility values in patients with age-related macular degeneration (ARMD) associated with visual impairments, by using preference-based measures of health. METHOD: This was a cross-sectional study involving patients with unilateral or bilateral ARMD who attended a large teaching hospital. Patients underwent visual tests (near and distant visual acuity [VA] and contrast sensitivity [CS]) and completed health status questionnaires including the Index of Visual Function (VF)-14 and three preference-based measures (the Health Utilities Index Mark III [HUI-3], the EuroQoL Health Questionnaire [EQ-5D], and the Short Form 6D Health Status Questionnaire [SF-6D]) and the time tradeoff (TTO). The mean health status is presented for five groups, defined according to the VA in the better-seeing eye and for four CS groups. RESULTS: Two hundred nine patients were recruited with substantial loss of visual function as obtained by visual tests (mean decimal VA in the better-seeing eye: 0.2) and self-report (mean VF-14 score: 41.5). The mean (+/-SD) utilities were 0.34 +/- 0.28 for HUI-3, 0.66 +/- 0.14 for SF-6D, 0.72 +/- 0.22 for EQ-5D, and 0.64 +/- 0.31 for TTO. The HUI-3 had the highest correlation with VA and CS (0.40 and -0.34), followed by TTO (0.25 and -0.21). Across the VA and CS groups, only HUI3 and TTO had a significant linear trend (P < 0.05). In a regression model with CS and VA as explanatory variables, only the coefficient on CS was statistically significant. CONCLUSIONS: ARMD is associated with a substantial impact on patients' health status, but this was not reflected in two of the generic preference-based measures used. The HUI-3 seems to be the instrument of choice for use in economic evaluations in which community data are needed. It may be more appropriate to base economic models on CS or some combination of CS and VA rather than on VA alone.

Aged↗

A comparison of four indirect methods of assessing utility values in rheumatoid arthritis.

OBJECTIVES: Utility scores can be assessed indirectly using preference-based instruments and used as weightings for quality-adjusted life years in economic analyses. It is not clear whether available instruments yield similar results or what domains of health are contributing to the overall score in a sample of patients with rheumatoid arthritis (RA). SUBJECTS: Our study included 313 individuals with rheumatologist-confirmed RA. MEASURES: A self-completed survey that permitted scoring of 4 indirect utility instruments (the Health Utilities Index Mark 2 and 3 (HUI-2 and HUI-3), the EuroQoL (EQ-5D), and the Short Form 6D (SF-6D) was the basis of our study. RESULTS: Mean (standard deviation) global utility scores were 0.63 (0.24) for the SF-6D, 0.66 (0.13) for the EQ-5D, 0.71 (0.19) for the HUI-2, and 0.53 (0.29) for the HUI-3 (P = 0.02 by repeated-measures analysis of variance). The intraclass correlation across all the indices was 0.67 (95% confidence interval 0.62-0.71). Bland-Altman plots revealed that agreement among instruments was poor at lower utility values. In this elderly RA sample, all of the global utilities mostly measured functional ability and pain. CONCLUSIONS: There are significant differences in utilities obtained from different indirect methods. Agreement among the instruments was moderate but poorer at lower utilities. It is unlikely that these utility values, if used as the weightings for quality-adjusted life years, would result in comparable estimates.

Activities of Daily Living↗

The estimation of a preference-based measure of health from the SF-12.

BACKGROUND: The SF-12 is a multidimensional generic measure of health-related quality of life. It has become widely used in clinical trials and routine outcome assessment because of its brevity and psychometric performance, but it cannot be used in economic evaluation in its current form. OBJECTIVES: We sought to derive a preference-based measure of health from the SF-12 for use in economic evaluation and to compare it with the original SF-36 preference-based index. RESEARCH DESIGN: The SF-12 was revised into a 6-dimensional health state classification (SF-6D [SF-12]) based on an item selection process designed to ensure the minimum loss of descriptive information. SUBJECTS: A sample of 241 states defined by the SF-6D (of 7500) have been valued by a representative sample of 611 members of the UK general population using the standard gamble (SG) technique. ANALYSIS: Models are estimated of the relationship between the SF-6D (SF-12) and SG values and evaluated in terms of their coefficients, overall fit, and the ability to predict SG values for all health states. RESULTS: The models have produced significant coefficients for levels of the SF-6D (SF-12), which are robust across model specification. The coefficients are similar to those of the SF-36 version and achieve similar levels of fit. There are concerns with some inconsistent estimates and these have been merged to produce the final recommended model. As for the SF-36 model, there is evidence of over prediction of the value of the poorest health states. CONCLUSIONS: The SF-12 index provides a useful tool for researchers and policy makers wishing to assess the cost-effectiveness of interventions.

Aged↗

Cost effectiveness of a community based exercise programme in over 65 year olds: cluster randomised trial.

OBJECTIVE: To assess the cost effectiveness of a community based exercise programme as a population wide public health intervention for older adults. DESIGN: Pragmatic, cluster randomised community intervention trial. SETTING: 12 general practices in Sheffield; four randomly selected as intervention populations, and eight as control populations. PARTICIPANTS: All those aged 65 and over in the least active four fifths of the population responding to a baseline survey. There were 2283 eligible participants from intervention practices and 4137 from control practices. INTERVENTION: Eligible subjects were invited to free locally held exercise classes, made available for two years. MAIN OUTCOME MEASURES: All cause and exercise related cause specific mortality and hospital service use at two years, and health status assessed at baseline, one, and two years using the SF-36. A cost utility analysis was also undertaken. RESULTS: Twenty six per cent of the eligible intervention practice population attended one or more exercise sessions. There were no significant differences in mortality rates, survival times, or admissions. After adjusting for baseline characteristics, patients in intervention practices had a lower decline in health status, although this reached significance only for the energy dimension and two composite scores (p<0.05). The incremental average QALY gain of 0.011 per person in the intervention population resulted in an incremental cost per QALY ratio of 17 174 (95% CI = 8300 to 87 120). CONCLUSIONS: Despite a low level of adherence to the exercise programme, there were significant gains in health related quality of life. The programme was more cost effective than many existing medical interventions, and would be practical for primary care commissioning agencies to implement.

Aged↗

What is the relationship between the minimally important difference and health state utility values? The case of the SF-6D.

BACKGROUND: The SF-6D is a new single summary preference-based measure of health derived from the SF-36. Empirical work is required to determine what is the smallest change in SF-6D scores that can be regarded as important and meaningful for health professionals, patients and other stakeholders. OBJECTIVES: To use anchor-based methods to determine the minimally important difference (MID) for the SF-6D for various datasets. METHODS: All responders to the original SF-36 questionnaire can be assigned an SF-6D score provided the 11 items used in the SF-6D have been completed. The SF-6D can be regarded as a continuous outcome scored on a 0.29 to 1.00 scale, with 1.00 indicating "full health". Anchor-based methods examine the relationship between an health-related quality of life (HRQoL) measure and an independent measure (or anchor) to elucidate the meaning of a particular degree of change. One anchor-based approach uses an estimate of the MID, the difference in the QoL scale corresponding to a self-reported small but important change on a global scale. Patients were followed for a period of time, then asked, using question 2 of the SF-36 as our global rating scale, (which is not part of the SF-6D), if there general health is much better (5), somewhat better (4), stayed the same (3), somewhat worse (2) or much worse (1) compared to the last time they were assessed. We considered patients whose global rating score was 4 or 2 as having experienced some change equivalent to the MID. In patients who reported a worsening of health (global change of 1 or 2) the sign of the change in the SF-6D score was reversed (i.e. multiplied by minus one). The MID was then taken as the mean change on the SF-6D scale of the patients who scored (2 or 4). RESULTS: This paper describes the MID for the SF-6D from seven longitudinal studies that had previously used the SF-36. CONCLUSIONS: From the seven reviewed studies (with nine patient groups) the MID for the SF-6D ranged from 0.010 to 0.048, with a weighted mean estimate of 0.033 (95% CI: 0.029 to 0.037). The corresponding Standardised Response Means (SRMs) ranged from 0.11 to 0.48, with a mean of 0.30 and were mainly in the "small to moderate" range using Cohen's criteria, supporting the MID results. Using the half-standard deviation (of change) approach the mean effect size was 0.051 (range 0.033 to 0.066). Further empirical work is required to see whether or not this holds true for other patient groups and populations.

Aged↗

Health-related quality of life and cost impact of irritable bowel syndrome in a UK primary care setting.

OBJECTIVES: To identify the impact of irritable bowel syndrome (IBS) on health-related quality of life (HR-QOL), time off work and the utilisation and cost of health services. DESIGN: A case-control study was undertaken matching patients with IBS and controls. Quality-of-life information was collected using the Medical Outcomes Study 36-item Short Form (SF-36) health survey, EuroQOL instrument (EQ-5D) and IBS Quality-of-Life (IBS-QOL) instruments. Data on time off work was also collected. National Health Service (NHS) resource use in primary and secondary care was estimated by review of general practitioner (GP) and hospital records over a 12-month period. SETTING: Recruitment was from six GPs' surgeries in the Trent Region of the United Kingdom. PARTICIPANTS: 161 patients with IBS, as defined by the Rome Criteria I were recruited. These were compared with 213 controls matched for age, sex and social characteristics. MAIN OUTCOME MEASURES: SF-36 and EQ-5D scores; mean number of days off work; mean NHS costs per person during the 12-month study period. RESULTS: Patients with IBS had considerably lower HR-QOL than controls. They scored worse in all dimensions of the SF-36 and the EQ-5D and they had more time off work. On average patients with IBS cost the NHS 123 UK pounds (95% confidence interval: 35 UK pounds to 221 UK pounds, 1999 values) more per year than individuals in the control group (p = 0.04). CONCLUSIONS: IBS affects patients through reduced quality of life, more time off work and greater healthcare utilisation than a control group of patients without IBS. The difference in quality of life was pronounced and unusual in that it was influential in every dimension of both the SF-36 and the EQ-5D.

Adult↗

Estimating a preference-based single index for the Impact of Weight on Quality of Life-Lite (IWQOL-Lite) instrument from the SF-6D.

OBJECTIVE: To facilitate economic evaluations of interventions for treating obesity, we estimated a preference-based single index for the Impact of Weight on Quality of Life-Lite (IWQOL-lite) instrument by mapping it onto the SF-6D preference-based index. METHODS: A heterogeneous sample of 1972 individuals, composed of community volunteers and participants in weight loss programs, clinical trials, and gastric bypass studies, completed the IWQOL-lite, an obesity-specific measure of health-related quality of life (HRQOL), and the SF-36, a generic measure of HRQOL converted into the preference-based SF-6D. Models of the relationship between the IWQOL-lite and SF-6D of increasing complexity were estimated by regression analyses. RESULTS: The best fitting model for predicting SF-6D index scores entered levels for each item as independent variables (R2 =0.530 in the cross-validation sample, with a mean absolute error of 0.0976). This model (1) makes fewer assumptions than those using total score, dimension scores or item scores as dependent variables and (2) provides a robust unbiased estimate of a preference-based index from IWQOL-Lite data where a preference-based measure was not used. The addition of age and body mass index (BMI) led to a slight improvement in the model. CONCLUSIONS: It is possible to facilitate economic evaluations using results obtained from disease-specific instruments using this approach. A weakness of this approach is that there may be aspects of the condition that have not been properly reflected in the SF-6D index. It is, however, useful when a preference-based measure has not been administered and when it would be impractical to conduct a full valuation survey.

Adolescent↗

Comparison of the HUI3 with the SF-36 preference based SF-6D in a clinical trial setting.

OBJECTIVE: To test the hypothesis that the Health Utilities Index Mark III (HUI3) and the SF-6D, based on the SF-36, generate similar health state values, and to test and compare their discriminant validity and responsiveness. METHODS: The HUI3 and SF-36 were administered to 331 patients enrolled in a double-blind, multinational phase III clinical trial in patients undergoing percutaneous coronary intervention before hospital discharge and 6 months thereafter. RESULTS: The mean SF-6D baseline health state score was 0.67 compared to the HUI3 of 0.63 with r of 0.616 and intraclass correlation coefficient of 0.40. The relationship was nonlinear with greatest divergence found at the lower levels of health. Both measures were found to agree with known differences in health and to be responsive to changes over time. Nevertheless, disagreement resulted in different estimates of change from baseline (0.08 vs. 0.154). CONCLUSION: Both measures deployed in the present study were found to have discriminant validity, and to be responsive to changes over time in coronary artery disease conditions. Nevertheless, the measures generated different estimates of health state values for this patient population. These differences might in part be the consequence of the health status descriptive system for the HUI that may have been more in line with the hospitalized state than that for the SF-6D. These findings seemed to indicate that measures deployed are not interchangeable for use in cost-utility analysis. More head-to-head comparisons between these two measures are needed to further define and compare relationships in different patient populations.

Adult↗