Time to tweak the TTO: results from a comparison of alternative specifications of the TTO

Abstract This article examines the effect that different specifications of the time trade-off (TTO) valuation task may have on values for EQ-5D-5L health states. The new variants of the TTO, namely lead-time TTO and lag-time TTO, along with the classic approach to TTO were compared using two durations for the health states (15 and 20 years). The study tested whether these methods yield comparable health-state values. TTO tasks were administered online. It was found that lag-time TTO produced lower values than lead-time TTO and that the difference was larger in the longer time frame. Classic TTO values most resembled those of the lag-time TTO in a 20-year time frame in terms of mean absolute difference. The relative importance of different domains of health was systematically affected by the duration of the health state. In the tasks with a 10-year health-state duration, anxiety/ depression had the largest negative impact on health-state values; in the tasks with a 5-year duration, the pain/discomfort domain had the largest negative impact

The human neonatal small intestine has the potential for arginine synthesis; developmental changes in the expression of arginine-synthesizing and -catabolizing enzymes

BACKGROUND: Milk contains too little arginine for normal growth, but its precursors proline and glutamine are abundant; the small intestine of rodents and piglets produces arginine from proline during the suckling period; and parenterally fed premature human neonates frequently suffer from hypoargininemia. These findings raise the question whether the neonatal human small intestine also expresses the enzymes that enable the synthesis of arginine from proline and/or glutamine. Carbamoylphosphate synthetase (CPS), ornithine aminotransferase (OAT), argininosuccinate synthetase (ASS), arginase-1 (ARG1), arginase-2 (ARG2), and nitric-oxide synthase (NOS) were visualized by semiquantitative immunohistochemistry in 89 small-intestinal specimens. RESULTS: Between 23 weeks of gestation and 3 years after birth, CPS- and ASS-protein content in enterocytes was high and then declined to reach adult levels at 5 years. OAT levels declined more gradually, whereas ARG-1 was not expressed. ARG-2 expression increased neonatally to adult levels. Neurons in the enteric plexus strongly expressed ASS, OAT, NOS1 and ARG2, while varicose nerve fibers in the circular layer of the muscularis propria stained for ASS and NOS1 only. The endothelium of small arterioles expressed ASS and NOS3, while their smooth-muscle layer expressed OAT and ARG2. CONCLUSION: The human small intestine acquires the potential to produce arginine well before fetuses become viable outside the uterus. The perinatal human intestine therefore resembles that of rodents and pigs. Enteral ASS behaves as a typical suckling enzyme because its expression all but disappears in the putative weaning period of human infants

Introducing the composite time trade-off: a test of feasibility and face validity

__Abstract__ __Introduction__ This study was designed to test the feasibility and face validity of the composite time trade-off (composite TTO), a new approach to TTO allowing for a more consistent elicitation of negative health state values. __Methods__ The new instrument combines a conventional TTO to elicit values for states regarded better than dead and a lead-time TTO for states worse than dead. __Results__ A total of 121 participants completed the composite TTO for ten EQ-5D-5L health states. Mean values ranged from −0.104 for health state 53555 to 0.946 for 21111. The instructions were clear to 98 % of the respondents, and 95 % found the task easy to understand, indicating feasibility. Further, the average number of steps taken in the iteration procedure to achieve the point of indifference in the TTO and the average duration of each task were indicative of a deliberate cognitive process. __Conclusion__ Face validity was confirmed by the high mean values for the mild health states (>0.90) and low mean values for the severe states (<0.42). In conclusion, this study demonstrates the feasibility and face validity of the composite TTO in a face-to-face standardized computer-assisted interview setting

Pharmaceutical Cost Management in an Ambulatory Setting Using a Risk Adjustment Tool

© 2014 Vivas-Consuelo et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background Pharmaceutical expenditure is undergoing very high growth, and accounts for 30% of overall healthcare expenditure in Spain. In this paper we present a prediction model for primary health care pharmaceutical expenditure based on Clinical Risk Groups (CRG), a system that classifies individuals into mutually exclusive categories and assigns each person to a severity level if s/he has a chronic health condition. This model may be used to draw up budgets and control health spending. Methods Descriptive study, cross-sectional. The study used a database of 4,700,000 population, with the following information: age, gender, assigned CRG group, chronic conditions and pharmaceutical expenditure. The predictive model for pharmaceutical expenditure was developed using CRG with 9 core groups and estimated by means of ordinary least squares (OLS). The weights obtained in the regression model were used to establish a case mix system to assign a prospective budget to health districts. Results The risk adjustment tool proved to have an acceptable level of prediction (R2 0.55) to explain pharmaceutical expenditure. Significant differences were observed between the predictive budget using the model developed and real spending in some health districts. For evaluation of pharmaceutical spending of pediatricians, other models have to be established. Conclusion The model is a valid tool to implement rational measures of cost containment in pharmaceutical expenditure, though it requires specific weights to adjust and forecast budgets.This study was financed by a grant from the Fondo de Investigaciones de la Seguridad Social Instituto de Salud Carlos III, the Spanish Ministry of Health (FIS PI12/0037). The authors would like to thank members (Juan Bru and Inma Saurf) of the Pharmacoeconomics Office of the Valencian Health Department. The opinions expressed in this paper are those of the authors and do not necessary reflect those of the afore-named. Any errors are the authors' responsibility. We would also like to thank John Wright for the English editing.Vivas Consuelo, DJJ.; Usó Talamantes, R.; Guadalajara Olmeda, MN.; Trillo Mata, JL.; Sancho Mestre, C.; Buigues Pastor, L. (2014). Pharmaceutical Cost Management in an Ambulatory Setting Using a Risk Adjustment Tool. 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Dealing with the health state ‘dead’ when using discrete choice experiments to obtain values for EQ-5D-5L heath states - Springer

__Abstract__ __Objective__ : To evaluate two different methods to obtain a dead (0)—full health (1) scale for EQ-5D-5L valuation studies when using discrete choice (DC) modeling. __Method__ : The study was carried out among 400 respondents from Barcelona who were representative of the Spanish population in terms of age, sex, and level of education. The DC design included 50 pairs of health states in five blocks. Participants were forced to choose between two EQ-5D-5L states (A and B). Two extra questions concerned whether A and B were considered worse than dead. Each participant performed ten choice exercises. In addition, values were collected using lead-time trade-off (lead-time TTO), for which 100 states in ten blocks were selected. Each participant performed five lead-time TTO exercises. These consisted of DC models offering the health state ‘dead’ as one of the choices—for which all participants’ responses were used (DCdead)—and a model that included only the responses of participants who chose at least one state as worse than dead (WTD) (DCWTD). The study also estimated DC models rescaled with lead-time TTO data and a lead-time TTO linear model. __Results__ : The DCdead and DCWTD models produced relatively similar results, although the coefficients in the DCdead model were slightly lower. The DC model rescaled with lead-time TTO data produced higher utility decrements. Lead-time TTO produced the highest utility decrements. __Conclusions__: The incorporation of the state ‘dead’ in the DC models produces results in concordance with DC models that do not include ‘dead’

Canadian Valuation of EQ-5D Health States: Preliminary Value Set and Considerations for Future Valuation Studies

Background The EQ-5D is a preference based instrument which provides a description of a respondent's health status, and an empirically derived value for that health state often from a representative sample of the general population. It is commonly used to derive Quality Adjusted Life Year calculations (QALY) in economic evaluations. However, values for health states have been found to differ between countries. The objective of this study was to develop a set of values for the EQ-5D health states for use in Canada. Methods Values for 48 different EQ-5D health states were elicited using the Time Trade Off (TTO) via a web survey in English. A random effect model was fitted to the data to estimate values for all 243 health states of the EQ-5D. Various model specifications were explored. Comparisons with EQ-5D values from the UK and US were made. Sensitivity analysis explored different transformations of values worse than dead, and exclusion criteria of subjects. Results The final model was estimated from the values of 1145 subjects with socio-demographics broadly representative of Canadian general population with the exception of Quebec. This yielded a good fit with observed TTO values, with an overall R2 of 0.403 and a mean absolute error of 0.044. Conclusion A preference-weight algorithm for Canadian studies that include the EQ-5D is developed. The primary limitations regarded the representativeness of the final sample, given the language used (English only), the method of recruitment, and the difficulty in the task. Insights into potential issues for conducting valuation studies in countries as large and diverse as Canada are gained

Outpatient costs in pharmaceutically treated diabetes patients with and without a diagnosis of depression in a Dutch primary care setting

<p>Abstract</p> <p>Background</p> <p>To assess differences in outpatient costs among pharmaceutically treated diabetes patients with and without a diagnosis of depression in a Dutch primary care setting.</p> <p>Methods</p> <p>A retrospective case control study over 3 years (2002-2004). Data on 7128 depressed patients and 23772 non-depressed matched controls were available from the electronic medical record system of 20 general practices organized in one large primary care organization in the Netherlands. A total of 393 depressed patients with diabetes and 494 non-depressed patients with diabetes were identified in these records. The data that were extracted from the medical record system concerned only outpatient costs, which included GP care, referrals, and medication.</p> <p>Results</p> <p>Mean total outpatient costs per year in depressed diabetes patients were €1039 (SD 743) in the period 2002-2004, which was more than two times as high as in non-depressed diabetes patients (€492, SD 434). After correction for age, sex, type of insurance, diabetes treatment, and comorbidity, the difference in total annual costs between depressed and non-depressed diabetes patients changed from €408 (uncorrected) to €463 (corrected) in multilevel analyses. Correction for comorbidity had the largest impact on the difference in costs between both groups.</p> <p>Conclusions</p> <p>Outpatient costs in depressed patients with diabetes are substantially higher than in non-depressed patients with diabetes even after adjusting for confounders. Future research should investigate whether effective treatment of depression among diabetes patients can reduce health care costs in the long term.</p