Comparison of four value sets derived using different TTO and DCE approaches: application to the new region-specific PBM, AP-7D.

BACKGROUND: AP-7D is a newly developed preference-based measure (PBM) in East and Southeast Asia. However, no value set has been established yet. Comparison of the characteristics of value sets obtained by different methods is necessary to consider the most appropriate methodology for valuation survey of AP-7D. METHOD: We surveyed the general population's preference of AP-7D health states by four valuation methods (a) composite time trade-off (cTTO); (b) simple discrete choice experiment (DCE); (c) DCE with duration; and (d) ternary DCE. In Japan, we collected approximately 1,000 samples for cTTO tasks through a face-to-face survey and 2,500 samples for each of the three DCE tasks. Respondents were selected through quota sampling based on the sex and age. The cTTO data were analyzed using a linear mixed and tobit model; the DCE data were analyzed using a simple and panel conditional logit model. Where the results of the analysis showed inconsistencies, a constrained model was used. RESULTS: Since all the unconstrained models, except simple DCE, showed one or more inconsistencies, the constrained model was used for the analyses. The minimum values for the models were as follows: TTO model, -0.101; simple DCE model, -0.106; DCE with duration model, -0.706; ternary DCE model, -0.306. The score for the DCE with the duration model was much lower than that for the other models. Although the value sets for AP-7D differed among the four valuation methods, the ternary DCE model showed intermediate characteristics between those of the cTTO and DCE with duration models. As compared with to EQ-5D-5L, the distributions of all the scores on the Japanese AP-7D moved to the left. Although "Energy" was one of the domains with the least influence on the AP-7D score in all four models, "Burden to others" had the largest impact on the preferences. CONCLUSION: We constructed four value sets using different TTO and DCE methods. Our findings are expected not only to contribute to the development of AP-7D, but also other preference-based measures.

Is anchoring at 'dead' a theoretical requirement for health state valuation?

Values that accompany generic health measures are typically anchored at 1 = full health and 0 = dead. Some health states may then be considered 'worse than dead' (WTD) and assigned negative values, which causes fundamental measurement problems. In this paper, we challenge the assumption that anchoring values at 'dead = 0' is necessary for quality-adjusted life year (QALY) estimation. We summarise the role of 'dead' in health state valuation and consider three critical questions: (i) whether the measurement properties of health state values require 'dead'; (ii) whether 'dead' needs to be valued relative to health states; and (iii) whether values for states WTD are meaningful or useful. We conclude that anchoring 0 at dead is not a requirement of health status measurement or cost-effectiveness analysis. This results from reframing QALYs as the relevant unit of measurement and reframing values as being derived from QALYs rather than the reverse.

Sulcus-deepening trochleoplasty grants satisfactory results with minimal patellofemoral arthritis at 23-30 years of follow-up.

PURPOSE: The purpose of this study was to evaluate the radiographic and clinical outcomes of sulcus-deepening trochleoplasty at a minimum follow-up of 23 years. METHODS: The authors evaluated a retrospective series of 10 patients (11 knees) who underwent trochleoplasty between 1993 and 2000. All patients were assessed at a minimum follow-up of 23 years by an independent clinician who noted any patellar redislocations and collected the International Knee Documentation Committee (IKDC), Kujala scores and range of motion. Radiographic examination was performed to assess patellofemoral arthritis using the Iwano classification. RESULTS: A total of 11 knees, from five women and five men aged 25.6 ± 6.9 years (range, 15-47 years) underwent trochleoplasty during the inclusion period. All 11 knees underwent adjuvant procedures during trochleoplasty (100%): 10 had tibial tuberosity osteotomy (TTO) and vastus medialis plasty and 1 had only vastus medialis plasty (had prior TTO). At a follow-up of 24.4 ± 2.1 years (range, 23-30 years), two patients were lost to follow-up (18%). The Iwano classification was Grade 1 in three patients (33%), Grade 2 in four patients (44%) and Grade 4 in two patients (22%). The flexion range was 130 ± 8.7° and satisfaction was 9.2 ± 0.7, Kujala was 76.9 ± 8.5 and IKDC was 65.5 ± 13.8. CONCLUSION: At 23-30 years following sulcus-deepening trochleoplasty in this small series of 10 patients (11 knees), patients had satisfactory clinical scores, only 1 patient reported an episode of traumatic patellar dislocation, and two knees had patellofemoral arthritis of Iwano Grade >2 (22%). LEVEL OF EVIDENCE: Level IV.

Increased tibial tuberosity torsion has the greatest predictive value in patients with patellofemoral instability compared to other commonly assessed parameters.

PURPOSE: The multifactorial nature of patellofemoral instability requires a comprehensive assessment of the affected patients. While an association between tibial tuberosity (TT) torsion and patellofemoral instability is known, its specific effect has not yet been investigated. This study investigated the effect of TT torsion on patellofemoral instability. METHODS: This retrospective cohort study compared patients who underwent surgical intervention for patellofemoral instability and asymptomatic controls. TT torsion was measured in addition to other commonly assessed risk factors for patellofemoral instability using standardised computed tomography (CT) data of the lower extremities. The diagnostic performances of the assessed parameters were evaluated using receiver operating characteristic curve analysis and odds ratios (ORs) were calculated. RESULTS: The patellofemoral instability group consisted of 79 knees, compared to 72 knees in the asymptomatic control group. Both groups differed significantly in all assessed parameters (p < 0.001), except for tibial torsion (n.s.). Among all parameters, TT torsion presented the best diagnostic performance for predicting patellar instability with an area under the curve of 0.95 (95% confidence interval [CI], 0.91-0.98; p < 0.001). A cut-off value of 17.7° yielded a 0.87 sensitivity and 0.89 specificity to predict patellar instability (OR, 55.2; 95% CI, 20.5-148.6; p < 0.001). CONCLUSION: Among the evaluated risk factors, TT torsion had the highest predictive value for patellofemoral instability. Patients with TT torsions ≥ 17.7° showed a 55-fold increased probability of patellofemoral instability. Therefore, TT torsion should be included in the assessment of patients with patellofemoral instability. LEVEL OF EVIDENCE: Level III.

Censoring Time Trade-off Values at 0 Versus at -1: How Does the Assumption for Worse-Than-Dead Time Trade-off Values Affect the Modeling of EQ-5D-5L Valuation Data?

OBJECTIVES: A recent study found that negative utility values elicited using composite time trade-off (TTO) were barely associated with the severity of EQ-5D-5L health states, suggesting poor discriminative ability. Assuming negative values provide limited information, this study aimed to explore the usefulness of censoring negative TTO values at 0 in modeling EQ-5D-5L valuation data. METHODS: We analyzed EQ-5D-5L valuation data from China, The Netherlands, Canada, Singapore, and Thailand. For each data set, we estimated value sets using 2 Tobit models, one left-censored at -1 (current practice) and one left-censored at 0 (our proposed method), and compared the model performances. We hypothesized that censoring at 0 and censoring at -1 would produce similar values, though on slightly different scales. RESULTS: When censoring at 0, logical inconsistencies and statistical significance were improved but the value range was compressed. In the cross-attribute level effects model, the 3-level parameters were similar between the models censored at 0 and -1, but the rank order of some dimension parameters was altered. Health state values predicted by the 2 censoring models approximated a perfect agreement after rescaling. CONCLUSIONS: Censoring TTO values at 0 improved model estimation and fit but produced higher utility values than models censoring at -1. Investigators of future EQ-5D value set studies using the composite TTO method are advised to examine the validity of negative TTO values before choosing modeling strategies.

Isolated medial patellofemoral ligament reconstruction results in similar postoperative outcomes as medial patellofemoral ligament reconstruction and tibial-tubercle osteotomy: a systematic review and meta-analysis.

PURPOSE: To determine the effect of isolated medial patellofemoral ligament reconstruction (MPFLR) versus concomitant MPFLR and tibial-tubercle osteotomy (TTO) on patient-reported functional outcomes, rate of patellar redislocation, and rate of return to sport in skeletally mature patients with recurrent patellar instability and lateralization as defined by elevated tibial-tubercle trochlear groove (TT-TG) distance. METHODS: Three databases MEDLINE, PubMed and EMBASE were searched from inception to July 10th, 2022 for literature outlining the management of patients with TT-TG indices greater than 15 mm with either isolated MPFLR or concomitant MPFLR and TTO procedures. The authors adhered to the PRISMA and R-AMSTAR guidelines as well as the Cochrane Handbook for Systematic Reviews of Interventions. Data on functional outcomes via the Kujala anterior knee pain score, redislocation rates, return to sport rates, and complications were recorded. The MINORS score was used for all studies to perform a quality assessment of included studies. RESULTS: A total of 31 studies comprising 1405 patients (1452 knees) were included in this review. The mean Kujala score in 13 studies comprising 848 total patients in the isolated MPFLR group was 85.0 (range 80.9-97.5) compared to a score of 83.7 (range 77.2-94.0) in 14 studies comprising 459 patients in the concomitant group. The mean pooled redislocation rate in 19 studies examining isolated MPFLR procedures comprising 948 patients was 3.1% (95% CI 2.1-4.4%, I2 = 7%) as opposed to 3.2% (95% CI 1.9-5.0%, I2 = 0%) in 15 studies comprising 486 patients in the concomitant group. The mean pooled return to sport rate in seven studies with 472 total patients in the isolated MPFLR group was 82% (95% CI 78-86%, I2 = 16%) compared to a score of 92% (95% CI 78-99%, I2 = 58%) in four studies comprising 54 patients in the concomitant group. There were similar complication rates between both treatment groups, including range of motion deficits, fractures, infections, and graft failures. CONCLUSION: Isolated MPFLR leads to similar anterior knee pain, similar redislocation rates and lower return to sport rates than concomitant MPFLR and TTO procedures in patients with TT-TG distances greater than 15 mm. Information from this review can aid surgeons in their decision to choose MPFLR versus concomitant procedures for this patient population, and can also guide future studies on this topic. LEVEL OF EVIDENCE: Level IV.

Valuing EQ-5D-Y: the current state of play.

BACKGROUND: For nearly a decade, value sets for the EQ-5D-Y were not available, reflecting challenges in valuing child HRQoL. A methodological research programme led to publication of a valuation protocol in 2020, which was rapidly taken up by local study teams. By the end of 2022, between 11 and 17 EQ-5D-Y value sets will be available, more than for any other child HRQoL measure. It is timely to review the experience of those using the protocol to identify early learnings and remaining issues where more research is needed. METHODS: In June 2021, the EuroQol Group organised a three-day workshop, bringing together all those involved in EQ-5D-Y value set studies and related methodological research concerning EQ-5D-Y and valuation. Workshop discussions were captured by note taking and recording all sessions and online chat. A narrative summary of all sessions was produced and synthesised to identify points of agreement and aspects of methods where uncertainty remains. RESULTS: There was broad agreement that DCE is working well as the principal valuation method. However, the most appropriate means of anchoring the latent scale values produced by DCE remains unclear. Some studies have deviated from the protocol by extending the number of states included in TTO tasks, to better support modelling of DCE and TTO. There is ongoing discussion about the relative merits of alternative variants of TTO and other methods for anchoring. Very few studies have consulted with local end-users to gauge the acceptability of methods used to value EQ-5D-Y. CONCLUSIONS: Priority areas for research include testing alternative methods for anchoring DCE data; exploring the preferences of adolescents; and scale differences in values for EQ-5D-Y and adult EQ-5D states, and implications of such differences for the use of EQ-5D-Y values in HTA. Given the normative elements of the protocol, engaging with HTA bodies and other local users should be the first step for all future value set studies. Value sets undertaken to date are for the three-level EQ-5D-Y. However, the issues discussed in this paper are equally relevant to valuation of the five-level version of EQ-5D-Y; indeed, similar challenges are encountered valuing any measure of child HRQoL.

Japanese preference weights of the Adult Social Care Outcomes Toolkit for Carers (ASCOT-Carer).

PURPOSE: We developed preference weights of the Adult Social Care Outcomes Toolkit for Carers (ASCOT-Carer) in Japan. METHODS: We used best-worst scaling (BWS) and composite time trade-off (cTTO) to determine the preference weights for ASCOT-Carer states in the general population. TTO values were applied to convert the BWS scores to utilities. The sample number was approximately 1000 for the BWS survey and 200 for the TTO survey. Whereas face-to-face surveys by computer-assisted interviewing were adopted for the TTO tasks, a web-based survey was used for the BWS tasks. In the BWS tasks, the ASCOT-Carer states were presented, and the "best," "worst," "second best," and "second worst" domains in a profile were selected. A mixed logit model was applied to the BWS data. RESULTS: The respondents' background was similar to that of the general population, although the number of people in the age and sex categories was equal. The preference weights for calculating the utilities of the ASCOT-Carer states were estimated. The estimated utilities of the ASCOT-Carer states were distributed between 1 and 0.02. All preference weights were consistent. The item with the highest preference weight was level 1 in the "space and time to be yourself." The least preferred item was level 4 in the "space and time to be yourself" and "control over daily life" domains. CONCLUSION: We established Japanese preference weights for ASCOT-Carer states, the first weights of an Asian country. The estimated utilities can contribute to the measurement of caregivers' social care-related QoL and perform of cost-effectiveness analyses.

Immune checkpoint inhibitors and potential risk of thromboembolic events: Analysis of the WHO global database of individual case safety reports.

Introduction: Thromboembolic events with the use of immune checkpoint inhibitors (ICIs) in patients with cancer have been reported in few studies. However, the detailed profile of these cases remains mostly uncertain. Method: A descriptive analysis of Thromboembolic events associated with ICIs retrieved from the VigiBase, between 1967 to November 2020. We extracted the data using the terms of 'pulmonary embolism' OR 'deep vein thrombosis' OR 'acute coronary syndrome' OR 'myocardial infarction' OR 'ischemic stroke' (preferred term (PT) (MedDRA). Results: We included 161 cases from 26 countries in our descriptive analysis. Patients' ages were reported in 141 (87.6%) cases, with a median of 68 years (interquartile range 61-74), and 63.4% of the patients were male. Indications for ICIs were reported in 151 (93.8%) cases, as follows: lung cancer (n = 85, 52.8%), renal cell carcinoma (n = 24, 14.9%), melanoma (n = 20, 12.4%), urethral carcinoma (n = 12, 7.45%), breast cancer (n = 4, 2.48%), adenocarcinoma of the gastroesophageal junction (n = 3, 1.9%), gastric cancer (n = 2, 1.24%), and skin cancer (n = 1, 0.62%). Nivolumab was reported as a suspected drug in 76 cases (47%), pembrolizumab in 46 cases (28.5%), atezolizumab in 21 cases (13%), durvalumab in 14 cases (8.6%), and avelumab in four cases (2.4%).The time to onset of thromboembolic events was reported in 127 (78.8%) cases. Most of these patients (n = 109, 85.8%) reported thromboembolic events within the first six months. The causality assessment of included cases showed that 50.3% of reported thromboembolic events were possibly related to the suspected reported medication, 13.7% were probably related, 13% were unlikely to be related, and 23% were not assessable due to insufficient information. Conclusion: This study demonstrates a possible association between the use of ICIs and thromboembolic events. Further epidemiological studies are needed to assess this association and to elucidate the underlying mechanism.

Rosin modified aminated mesoporous silica adsorbed tea tree oil sustained-release system for improve synergistic antibacterial and long-term antibacterial effects.

Tea tree oil, a natural antibacterial compound, cannot be used effectively because of its volatile nature. In this work, a biocompatible carrier was prepared and loaded with tea tree essential oil. The carrier was prepared via the electrostatic or chemical action of aminated mesoporous silica and sodium rosin for achieving a low volatilization rate of tea tree essential oil. A synergistic antibacterial effect was observed between sodium rosin and tea tree essential oil. This method utilized the positive charge of the amino group and the condensation reaction with the carboxyl group to achieve physical and chemical interactions with sodium rosin. Fourier Transform Infrared, Brunauer-Emmet-Teller, Zeta potential, SEM, TEM, and TG were performed to characterize the structure and properties of the samples. Compared to the electrostatic effect, the chemically modified system exhibited a longer sustained release, and the sustained release curve followed the Korsmeyer-Peppas release model. Also, the antibacterial properties of the chemically modified system exhibited better minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) respectively, the MIC and MBC forE. coliwere 0.3 mg ml-1and 0.6 mg ml-1respectively, forS. aureuswere 0.15 mg ml-1and 0.3 mg ml-1respectively. More strikingly, the sample also demonstrated long-term antibacterial performance. Therefore, this work provides a new way for the delivery of volatile antibacterial drugs to achieve sustained-release and long-lasting antibacterial effects.

Using the Choice Sequence in Time Trade-Off as Discrete Choices: Do the Two Stories Match?

OBJECTIVES: The EQ-5D-5L valuation protocol recommends combining time trade-off (TTO) and discrete choice experiments (DCEs). DCEs that include a duration attribute (DCETTO) allow modeling on the quality-adjusted life-year scale. Because the choice sequence in a TTO can be construed as a series of DCETTO, we used data from a single TTO study to investigate the extent to which DCE values match TTO values when based on identical preferences. METHODS: In a TTO design in which a fixed set of choices were administered without termination at preference indifference, 202 individuals each valued 10 EQ-5D health states. From identified indifference points, we estimated three sets of TTO values: (i) plotting means and (ii) applying censored regressions at -1 and 1. Using all strict preferences, we (iii) estimated DCETTO values with a logit model and a bootstrap procedure. RESULTS: Estimated DCETTO and TTO values agreed well at the severe end of the quality-adjusted life-year scale, but with decreasing severity, DCETTO values were higher than TTO-values, with the difference peaking at 0.37 for the mildest health state. Left-censoring TTO values at -1 worsen the agreement for the worst health states and did not affect health states. Right censoring at 1 improved the agreement for mild states. CONCLUSIONS: TTO and the DCETTO values estimated from the same preference data diverged, with increasing difference for milder health states. Although the values converged when applying censored regression at +1, we question the validity of this adjustment.

Similar responses to EQ-5D-3L by two elicitation methods: visual analogue scale and time trade-off.

BACKGROUND: Health-related quality of life (HRQoL) is often measured using EQ-5D-3L by the elicitation methods of visual analogue scale (VAS) and time trade-off (TTO). Although many countries have constructed both national VAS and TTO value sets, the fact that VAS and TTO value sets produces different values bewilders researchers and policymakers. The aim of this study is to explore certain conditions which could yield similar value sets using VAS and TTO. METHODS: A homogeneous sample of medical school students was selected to value 18 hypothetical health states using VAS and TTO methods. The 18 hypothetical health states were produced by orthogonal design (L18, 2*3^7). The range of rescaled values was transformed into - 1 ~ 0 ~ 1. The investigations via different methods were carried out by computer-assisted personal interviewing with a wash-time interval of 72 h. Value sets for VAS and TTO were constructed using general least square regression models. Independent variables were composed of 10 dummy variables from 5 dimensions and including or omitting both constant and N3 terms. RESULTS: Three hundred thirteen medical students participated. The mean age was 21.03 ± 0.44 years and 56.2% were female. The four regression models (for each method with and without constant and N3 terms) were all statistically significant (P < 0.05) with high goodness-of-fit (Adj. R2 > 0.94 and MAE < 0.033). Differences between the coefficients of the 10 dummy variables corresponding to each model were all less than 0.059. Pearson correlation coefficients between observed means and predicted values exceeded 0.981. Fitted curves of VAS and TTO largely coincided. CONCLUSIONS: VAS and TTO can generate similar responses under certain conditions, suggesting that the two valuation methods could be equivalent intrinsically. The VAS method appears a more valid approach for valuation in the general population due to its greater simplicity and feasibility.

Influence of elicitation procedure and phrasing on health state valuations in experience-based time trade-off tasks among diabetes patients in China.

PURPOSE: Open-ended and iteration-based time trade-off (TTO) tasks can both be used for valuation of health states. It has so far not been examined how the elicitation procedure affects the valuation of experience-based health states. The purpose of this study is to investigate the influence of elicitation procedure on experience-based health state values elicited by the TTO method. METHODS: 156 Chinese adults with type 2 diabetes participated in face-to-face interviews with an open-ended or an iteration-based TTO task. The association between the type of TTO task and the valuation of health states was investigated through multiple linear regression analyses. A modified open-ended TTO task was also developed (n = 33) to test whether different phrasings of open-ended TTO tasks influence TTO values. RESULTS: Higher TTO values were observed in the original open-ended TTO task compared to the iteration-based task, which indicates that the elicitation procedure influences the valuation of health states. When the modified open-ended task was introduced, the difference between the two elicitation procedures was no longer statistically significant, suggesting that the phrasing and/or visual presentation of the TTO task may influence the valuation of health states. CONCLUSIONS: The choice of elicitation procedure as well as the description of experience-based TTO tasks may influence the valuation of health states. Further research is warranted, also in other cultural contexts, to further explore these findings.

Development of Japanese utility weights for the Adult Social Care Outcomes Toolkit (ASCOT) SCT4.

PURPOSE: In developed countries, progressive rapid aging is increasing the need for social care. This study aimed to determine Japanese utility weights for the Adult Social Care Outcomes Toolkit (ASCOT) four-level self-completion questionnaire (SCT4). METHODS: We recruited 1050 Japanese respondents from the general population, stratified by sex and age, from five major cities. In the best-worst scaling (BWS) phase, respondents ranked various social care-related quality of life (SCRQoL) states as "best," "worst," "second-best," or "second-worst," as per the ASCOT. Then, respondents were asked to evaluate eight different SCRQOL states by composite time-trade off (cTTO). A mixed logit model was used to analyze BWS data. The association between cTTO and latent BWS scores was used to estimate a scoring formula that would convert BWS scores to SC-QALY (social care quality-adjusted life year) scores. RESULTS: Japanese BWS weightings for ASCOT-SCT4 were successfully estimated and found generally consistent with the UK utility weights. However, coefficients on level 3 of "Control over daily life" and "Occupation" domains differed markedly between Japan and the UK. The worst Japanese SCRQoL state was lower than that for the UK, as Japanese cTTO results showed more negative valuations. In general, Japanese SC-QALY score (for more than 90% of health states) was lower than that for the UK. CONCLUSIONS: We successfully obtained Japanese utility weights for ASCOT SCT4. This will contribute to the measurement and understanding of social care outcomes.

A detaching, V-shaped tibial tubercle osteotomy is a safe procedure with a low complication rate.

INTRODUCTION: In patients with recurrent patellar dislocations, a tibial tubercle osteotomy (TTO) can be indicated to correct patella alta or an increased trochlear groove-tibial tubercle distance. Several surgical techniques are described. Previous studies emphasize that detaching osteotomies results in devascularisation, which can lead to non-union and tibial shaft fractures. The aim of this study was to report the complication rates directly related to the surgical technique of a V-shaped TTO, where the tubercle is completely released from its periosteum using a step-cut osteotomy. METHODS: The retrospective case series comprised a large cohort of 263 knees with patella alta in 203 patients who underwent a V-shaped TTO, with or without additional realignment procedures, between March 2004 and October 2017. Data were obtained from available patient files. Complications were defined as minor or major. RESULTS: Thirteen major complications were registered (4.9%) including two tibial fractures (0.75%) and one non-union (0.37%). Five complications (1.9%) were defined as minor. Removal of the screws because of irritation or pain was seen in 22 cases (8.2%). CONCLUSION: A V-shaped TTO is a safe procedure. The presumed higher risk for tibial fractures or pseudo-arthrosis could not be confirmed.

Valuation of Health States Considered to Be Worse Than Death-An Analysis of Composite Time Trade-Off Data From 5 EQ-5D-5L Valuation Studies.

OBJECTIVES: To evaluate the discriminative ability of negative values measured in 5-level EuroQol 5-dimensional questionnaire (EQ-5D-5L) value set studies. METHODS: This is a secondary analysis of EQ-5D-5L value set studies from Singapore, the Netherlands, China, Thailand, and Canada in which health state values were elicited from a general population sample using a composite time trade-off (TTO) method. Mean values were calculated for health states with same severity. The association between the mean values and severity was evaluated using Pearson correlation (r). A linear mixed model using severity as the fixed effect was fitted for values. The analyses were performed separately for positive values (from a conventional TTO for health states considered "better than death") and negative values (from a lead time TTO for health states considered "worse than death"). RESULTS: In Singapore (N = 1000; negative values 32.6%), the mean decreased with severity from 0.89 to 0.21 for positive values and increased with severity from -0.98 to -0.89 for negative values. The correlation between values and severity was much lower for negative values (r = -0.016) than for positive values (r = -0.614). The coefficient of severity in the linear mixed model for negative values was much smaller (coefficient = -0.009; pseudo-R2 < 0.001) compared with the model for positive values (coefficient = -0.041; pseudo-R2 = 0.337). Results using data sets from the other countries were similar. CONCLUSIONS: Negative values are not associated with severity of health states in EQ-5D-5L valuation studies, suggesting poor discriminative ability of the lead time TTO method in valuing health states considered worse than death.

Toward a Smaller Design for EQ-5D-5L Valuation Studies.

BACKGROUND: To construct an EQ-5D-5L value set, the EuroQol Group developed a standard protocol named EuroQol Valuation Technology (EQ-VT), prescribing the valuation of 86 health states utilizing the composite time trade-off (cTTO) approach, and subsequently modeled the observed values to yield values for all 3125 states. OBJECTIVE: A recent study demonstrated that a 25-state orthogonal design could provide as accurate predictions as the EQ-VT design applying visual analogue scale data. We aimed to test that design using time trade-off (TTO) data. METHOD: We collected TTO values utilizing EQ-VT, orthogonal, and D-efficient designs. The EQ-VT design included 86 health states distributed over 3 blocks of 30 states with some duplicates. The orthogonal and D-efficient designs each comprised 1 block of 30 states. A total of 525 university students were asked to value a random block of health states using EQ-PVT (a PowerPoint replica of EQ-VT software), which generated 100 observations per health state in all 3 designs. We modeled data by design and compared the root mean square error (RMSE) between observed and predicted values within and across the designs. RESULTS: The EQ-VT design had the lowest RMSE of 0.052; the RMSEs for the orthogonal and the D-efficient designs were 0.066 and 0.063, respectively. RMSE results between designs differed for more severe health states. Some coefficients differed between designs. CONCLUSION: Smaller designs did not lead to significant increases in prediction errors when modeling TTO data (measuring 0.01 on a utility scale). Resource-constrained countries may use small designs for valuation studies, especially when other types of preference data, such as those from discrete choice experiments, are collected and modeled jointly.

Sequence effects in time trade-off valuation of hypothetical health states.

Choice-based stated preference methods, such as time trade-offs (TTOs), are used to establish health state utilities informing healthcare allocation. However, little is known about the presence of (position-dependent and precedent-dependent) sequence effects in the valuation of health states, despite techniques requiring respondents to evaluate several health states in a sequence. This paper is the first to explicitly test for the presence of sequence effects in the health domain using a new explanation based on contrast effects and preference imprecision; the implication being that randomisation cannot avoid sequence effects. Six TTO questions were designed using the EQ-5D-3L descriptive system. These were grouped into two blocks of three and within each block four sequences were used. In an online survey, 1,197 Spanish respondents answered one grouping of three TTO questions. Results indicate that sequence effects can affect preferences as utilities of health states are biased downwards if preceded by a better health state and biased upwards if preceded by a worse health state. This study informs our understanding of how context effects interact with preference elicitation methods, which is essential for interpreting survey results used to inform policy.

Enhanced Killing of Candida krusei by Polymorphonuclear Leucocytes in the Presence of Subinhibitory Concentrations of Melaleuca alternifolia and "Mentha of Pancalieri" Essential Oils.

The aim of this study was to evaluate the influence of tea tree oil (TTO) and "Mentha of Pancalieri" essential oil (MPP) on intracellular killing of Candida krusei, often resistant to conventional drugs, by polymorphonuclear leucocytes (PMNs). Intracellular killing was investigated by incubating yeasts and PMNs with essential oils (EOs) at 1/4 and 1/8 × MIC (Minimal Inhibitory Concentration), in comparison with anidulafungin, used as a reference drug. Killing values were expressed as Survival Index (SI) values. The cytotoxicity of EOs was evaluated by 3-[4,-5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Both EOs were more efficaceous at 1/8 × MIC than 1/4 × MIC, with killing values higher than observed in EO-free systems and in presence of anidulafungin, indicating that the decreasing concentrations did not cause lower candidacidal activity. This better activity at 1/8 × MIC is probably due to the EOs' toxicity at 1/4 × MIC, suggesting that at higher concentrations EOs might interfere with PMNs functionality. TTO and MPP at 1/8 × MIC significantly increased intracellular killing by PMNs through their direct action on the yeasts (both EOs) or on phagocytic cells (MPP), suggesting a positive interaction between EOs and PMNs to eradicate intracellular C. krusei. These data showed a promising potential application of TTO and "Mentha of Pancalieri" EO as natural adjuvants in C. krusei infection management.

Valuing health states: is the MACBETH approach useful for valuing EQ-5D-3L health states?

BACKGROUND: Quality Adjusted Life Years (QALYs) are a key outcome measure widely used within health technology assessment and health service research studies. QALYs combine quantity and quality of life, with quality of life calculations relying on the value of distinct health states. Such health states' values capture the preferences of a population and have been typically built through numerical elicitation methods. Evidence points to these value scores being influenced by methods in use and individuals reporting cognitive difficulties in eliciting their preferences. Evidence from other areas has further suggested that individuals may prefer using distinct elicitation techniques and that this preference can be influenced by their numeracy. In this study we explore the use of the MACBETH (Measuring Attractiveness by a Categorical Based Evaluation Technique) non-numerical preference elicitation approach for health states' evaluation. METHODS: A new protocol for preference elicitation based on MACBETH (only requiring qualitative judgments) was developed and tested within a web survey format. A sample of the Portuguese general population (n=243) valued 25 EQ-5D-3L health states with the MACBETH protocol and with a variant of the time trade-off (TTO) protocol, for comparison purposes and for understanding respondents' preference for distinct protocols and differences in inconsistent evaluations. Respondents answered to a short numeracy test, and basic socio-economic information collected. RESULTS: Results show that the mean values derived from MACBETH and the TTO variant are strongly correlated; however, there are substantial differences for several health states' values. Large and similar numbers of logical inconsistencies were found in respondents' answers with both methods. Participants with higher levels of numeracy according to the test preferred expressing value judgments with MACBETH, while participants with lower levels were mostly indifferent to both methods. Higher correlations between MACBETH and TTO variant evaluations were observed for individuals with higher numeracy. CONCLUSION: Results suggest that it is worth researching the use of non-numerical preference elicitation methods. Numeracy tests more appropriate for preference elicitation when no explicit considerations of uncertainty are made need to be explored and used. Further behavioural research is needed to fully understand the potential for using these methods in distinct settings (e.g. in different evaluation contexts and in face-to-face and non-face-to-face environments), as well as to explore the effect of literacy on assessments and on respondents' preferences.