Small differences in EQ-5D-5L health utility scores were interpreted differently between and within respondents.

OBJECTIVES: This study aims to determine how population-based health-utility score (HUS) differences reflect individuals' health preferences using responses from the Canadian EQ-5D-5L Valuation Study, including time trade-off (TTO) and discrete-choice experiment (DCE) tasks (n = 1073). STUDY DESIGN AND SETTING: Cardinal TTO responses were transformed into pairwise comparisons to yield ordinal TTO responses. We investigated how EQ-5D-5L HUS differences differ from participants' stated cardinal preferences, and determined the smallest HUS difference that may be expected to represent participants' ordinal preferences. RESULTS: HUS differences near zero have 30.6% (95% confidence interval: 29.1-31.9%) probability of representing a tie in individuals' TTO values. Differences in EQ-5D-5L HUS of -0.054 (-0.071 to -0.029) and 0.047 (0.026-0.076) maximized the sensitivity and specificity of discriminating transitions to worse/better health states. For small HUS differences of ±0.03 to ±0.07, the magnitude of respondents' average TTO difference on the cardinal scale was 0.17 and 0.35 whether ties were included or excluded, respectively. Absolute HUS differences between 0.042 and 0.062 had a 50% probability of representing respondents' ordinal preferences. CONCLUSION: A HUS needs to be large enough to reflect individuals' stated health preferences, which may lend support to the application of a minimally important difference for decision-making.

Modifying the quality-adjusted life year calculation to account for meaningful change in health-related quality of life: insights from a pragmatic clinical trial.

BACKGROUND: We propose a modified quality-adjusted life year (QALY) calculation that aims to be consistent with guidance for interpreting change in patient-reported outcomes. This calculation incorporates the minimally important difference (MID) in generic preference-based health-related quality of life (HRQL) change scores to reflect what might be considered meaningful HRQL improvement/deterioration. In doing so, we review common issues in QALY calculations such as adjustment for baseline scores and standardizing for between-group differences. METHODS: Using EQ-5D-5L outcome data from the Alberta TEAMCare-Primary Care Network trial in the management of depression for patients with type 2 diabetes (n = 98), this study compared results from different QALY calculation methods to investigate the impact of (i) adjusting for baseline HRQL score, (ii) standardizing between-group differences at baseline, and (iii) adjusting for 'meaningful' HRQL changes. The following QALY calculation methods are examined: area under curve (QALY-AUC), change from baseline (QALY-CFB), regression modelling (QALY-R), and incorporating an MID for HRQL changes from baseline (QALY-MID). RESULTS: The incremental QALY-AUC estimate favoured the Collaborative Care group (0.031) while the incremental QALY-CFB (-0.028) estimate favoured Enhanced Care. Adjusting for meaningful HRQL changes resulted in a crude incremental QALY-MID of -0.023; however, after adjusting for between-group differences at baseline, QALY-R and adjusted incremental QALY-MID estimates were -0.007 and -0.001, respectively. In addition, recursive regression analyses showed that very low baseline HRQL scores impact incremental QALY estimates. CONCLUSIONS: Uncertainty in incremental QALY estimates reflects uncertainty in the value of small within-individual change as well as the impact of small differences between groups at baseline. Applying a responder-definition approach yielded crude and adjusted QALY-MID estimates that were more in favour of Collaborative Care than QALY-CFB and QALY-R estimates, respectively, suggesting that ambiguous small changes in HRQL scores have the potential to influence QALY outcomes used in economic or non-economic applications.

Estimation of an Instrument-Defined Minimally Important Difference in EQ-5D-5L Index Scores Based on Scoring Algorithms Derived Using the EQ-VT Version 2 Valuation Protocols.

OBJECTIVES: To estimate and compare the minimally important difference (MID) in index score of country-specific EQ-5D-5L scoring algorithms developed using EuroQol Valuation Technology protocol version 2, including algorithms from Germany, Indonesia, Ireland, Malaysia, Poland, Portugal, Taiwan, and the United States. METHODS: A simulation-based approach contingent on all single-level transitions defined by the EQ-5D-5L descriptive system was used to estimate the MID for each algorithm. RESULTS: The resulting mean (and standard deviation) instrument-defined MID estimates were Germany, 0.083 (0.022); Indonesia, 0.093 (0.012); Ireland, 0.098 (0.023); Malaysia, 0.072 (0.010); Poland, 0.080 (0.030); Portugal, 0.080 (0.018); Taiwan, 0.101 (0.010); and the United States, 0.078 (0.014). CONCLUSIONS: These population preference-based MID estimates and accompanying evidence of how such values vary as a function of baseline index score can be used to aid interpretation of index score change. The marked consistency in the relationship between the calculated MID estimate and the range of the EQ-5D-5L index score, represented by a ratio of 1:20, might substantiate a rule of thumb allowing for MID approximation in EQ-5D-5L index score warranting further investigation.

A Longitudinal Study on the Association Between Diabetic Foot Disease and Health-Related Quality of Life in Adults With Type 2 Diabetes.

OBJECTIVES: The aim of this study was to assess the association between diabetic foot disease and health-related quality of life (HRQOL) during a 2-year follow up among people with type 2 diabetes in Alberta. METHODS: A type 2 diabetes cohort was established (2011‒2013); those with self-reported diabetic foot disease were identified. HRQOL was assessed at baseline and 1 and 2 years. Scores from the 12-item Short Form Physical Component Summary (PCS) and Mental Component Summary (MCS) and the EuroQol 5-Dimension 5-Level (EQ-5D-5L) instrument were collected. The association between diabetic foot disease and changes in HRQOL was assessed using the general linear mixed model after adjustment for sociodemographics, previous health-care use, Elixhauser comorbidities index, baseline health status and diabetes-specific behaviours. RESULTS: Among the cohort (n=969), average age was 64.3 (standard deviation, 10.0) years and 55% were male. Overall, 265 (27.4%) participants reported having diabetic foot disease. Those with diabetic foot disease reported lower HRQOL in comparison to those without diabetic foot disease at baseline: PCS, 8.44 (95% confidence interval [CI], 7.06 to 9.82); MCS, 4.33 (95% CI, 2.99 to 5.67) and EQ-5D-5L index score, 0.12 (95% CI, 0.09 to 0.14). After adjustment, no differences were observed in the score changes at year 2 (PCS, 0.16 [95% CI, -0.88 to 1.21]; MCS, 0.36 [95% CI, -0.77 to 1.50]; EQ-5D-5L index score, 0.004 [95% CI, -0.01 to 0.02]). CONCLUSIONS: Although participants with diabetic foot disease reported lower HRQOL at baseline, they had similar changes compared to those without diabetic foot disease during the 2-year follow up. Efforts to maintain general health and early intervention to prevent diabetic foot disease may help to avoid initial deterioration of physical health and HRQOL.

Minimally Important Difference of the EQ-5D-5L Index Score in Adults with Type 2 Diabetes.

BACKGROUND: The EuroQol five-dimensional questionnaire (EQ-5D) is a generic preference-based measure of health-related quality of life, and several studies have made attempts to estimate the minimally important difference (MID) for the EQ-5D index score. OBJECTIVES: To estimate the MID of the five-level EQ-5D (EQ-5D-5L) index score in a population-based sample of adults with type 2 diabetes and to explore whether the MID estimate varies by baseline index score and the direction of change in health status. METHODS: We used longitudinal survey data of adults with type 2 diabetes in Alberta, Canada. The EQ-5D-5L MID was estimated first by the instrument-defined approach, which used the difference between the baseline index scores and the index scores of simulated single-level transitions, and then by the anchor-based approach, which categorized 1-year changes in depressive symptoms, diabetes-related distress, as well as physical and mental health functioning into no change, small change, and large change groups, wherein the MID was estimated as the average change in index score of the small change group. RESULTS: Using the instrument-defined approach, MID estimates were 0.043, 0.040, and 0.045, whereas anchor-based MID estimates were 0.042, 0.034, and 0.049 for all change, improvement, and deterioration, respectively. Larger MID estimates were observed for lower baseline index scores and for deterioration in health status. CONCLUSIONS: MID estimates of the EQ-5D-5L index score were consistent between instrument-defined and anchor-based approaches and ranged between 0.03 and 0.05. Estimates varied by baseline index score and the direction of change, with similar results for patient subgroups.

Instrument-Defined Estimates of the Minimally Important Difference for EQ-5D-5L Index Scores.

BACKGROUND: The five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) is a preference-based measure of health-related quality of life (HRQOL), which yields an index score anchored at 0 (dead) and 1 (full health). We lack evidence on estimates for the minimally important difference (MID) of the EQ-5D-5L that will help in interpreting differences or changes in HRQOL measured by this scale score. OBJECTIVES: To estimate the MID of the EQ-5D-5L index score for available scoring algorithms including algorithms from Canada, China, Spain, Japan, England, and Uruguay. METHODS: A simulation-based approach based on instrument-defined single-level transitions was used to estimate the MID values of the EQ-5D-5L for each country-specific scoring algorithm. RESULTS: The simulation-based instrument-defined MID estimates (mean ± SD) for each country-specific scoring algorithm were as follows: Canada, 0.056 ± 0.011; China, 0.069 ± 0.007; Spain, 0.061 ± 0.008; Japan, 0.048 ± 0.004; England, 0.063 ± 0.013; and Uruguay, 0.063 ± 0.019. Differences in MID estimates reflect differences in population preferences, in valuation techniques used, as well as in modeling strategies. After excluding the maximum-valued scoring parameters, the MID estimates (mean ± SD) were as follows: Canada, 0.037 ± 0.001; China, 0.058 ± 0.005; Spain, 0.045 ± 0.009; Japan, 0.044 ± 0.004; England, 0.037 ± 0.008; and Uruguay, 0.040 ± 0.010. CONCLUSIONS: Simulation-based estimates of the MID of the EQ-5D-5L index score were generally between 0.037 and 0.069, which are similar to the MID estimates of other preference-based HRQOL measures.

A theoretical examination of the relative importance of evolution management and drug development for managing resistance.

Drug resistance is a serious public health problem that threatens to thwart our ability to treat many infectious diseases. Repeatedly, the introduction of new drugs has been followed by the evolution of resistance. In principle, there are two complementary ways to address this problem: (i) enhancing drug development and (ii) slowing the evolution of drug resistance through evolutionary management. Although these two strategies are not mutually exclusive, it is nevertheless worthwhile considering whether one might be inherently more effective than the other. We present a simple mathematical model that explores how interventions aimed at these two approaches affect the availability of effective drugs. Our results identify an interesting feature of evolution management that, all else equal, tends to make it more effective than enhancing drug development. Thus, although enhancing drug development will necessarily be a central part of addressing the problem of resistance, our results lend support to the idea that evolution management is probably a very significant component of the solution as well.