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1.  Induction of labour versus expectant monitoring in women with pregnancy induced hypertension or mild preeclampsia at term: the HYPITAT trial 
Hypertensive disorders, i.e. pregnancy induced hypertension and preeclampsia, complicate 10 to15% of all pregnancies at term and are a major cause of maternal and perinatal morbidity and mortality. The only causal treatment is delivery. In case of preterm pregnancies conservative management is advocated if the risks for mother and child remain acceptable. In contrast, there is no consensus on how to manage mild hypertensive disease in pregnancies at term. Induction of labour might prevent maternal and neonatal complications at the expense of increased instrumental vaginal delivery rates and caesarean section rates.
Women with a pregnancy complicated by pregnancy induced hypertension or mild preeclampsia at a gestational age between 36+0 and 41+0 weeks will be asked to participate in a multi-centre randomised controlled trial. Women will be randomised to either induction of labour or expectant management for spontaneous delivery. The primary outcome of this study is severe maternal morbidity, which can be complicated by maternal mortality in rare cases. Secondary outcome measures are neonatal mortality and morbidity, caesarean and vaginal instrumental delivery rates, maternal quality of life and costs. Analysis will be by intention to treat. In total, 720 pregnant women have to be randomised to show a reduction in severe maternal complications of hypertensive disease from 12 to 6%.
This trial will provide evidence as to whether or not induction of labour in women with pregnancy induced hypertension or mild preeclampsia (nearly) at term is an effective treatment to prevent severe maternal complications.
Trial Registration
The protocol is registered in the clinical trial register number ISRCTN08132825.
PMCID: PMC1950708  PMID: 17662114
2.  Should cervical favourability play a role in the decision for labour induction in gestational hypertension or mild pre-eclampsia at term? An exploratory analysis of the HYPITAT trial 
Bjog  2012;119(9):1123-1130.
To examine whether cervical favourability (measured by cervical length and the Bishop score) should inform obstetricians’ decision regarding labour induction for women with gestational hypertension or mild pre-eclampsia at term.
A post hoc analysis of the Hypertension and Pre-eclampsia Intervention Trial At Term (HYPITAT).
Obstetric departments of six university and 32 teaching and district hospitals in the Netherlands.
A total of 756 women diagnosed with gestational hypertension or pre-eclampsia between 36 + 0 and 41 + 0 weeks of gestation randomly allocated to induction of labour or expectant management.
Data were analysed using logistic regression modelling.
Main outcome measures
The occurrence of a high-risk maternal situation defined as either maternal complications or progression to severe disease. Secondary outcomes were caesarean delivery and adverse neonatal outcomes.
The superiority of labour induction in preventing high-risk situations in women with gestational hypertension or mild pre-eclampsia at term varied significantly according to cervical favourability. In women who were managed expectantly, the longer the cervix the higher the risk of developing maternal high-risk situations, whereas in women in whom labour was induced, cervical length was not associated with a higher probability of maternal high-risk situations (test of interaction P = 0.03). Similarly, the beneficial effect of labour induction on reducing the caesarean section rate was stronger in women with an unfavourable cervix.
Against widely held opinion, our exploratory analysis showed that women with gestational hypertension or mild pre-eclampsia at term who have an unfavourable cervix benefited more from labour induction than other women.
Trial registration
The trial has been registered in the clinical trial register as ISRCTN08132825.
PMCID: PMC3440582  PMID: 22703475
Bishop score; cervical length; expectant management; gestational hypertension; induction of labour; pre-eclampsia
3.  Obstetrical outcome valuations by patients, professionals, and laypersons: differences within and between groups using three valuation methods 
Decision-making can be based on treatment preferences of the patient, the doctor, or by guidelines based on lay people's preferences. We compared valuations assigned by three groups: patients, obstetrical care professionals, and laypersons, for health states involving both mother and (unborn) child. Our aim was to compare the valuations of different groups using different valuation methods and complex obstetric health outcome vignettes that involve both maternal and neonatal outcomes.
Patients (n = 24), professionals (n = 30), and laypersons (n = 27) valued the vignettes using three valuation methods: visual analogue scale (VAS), time trade-off (TTO), and discrete choice experimentation (DCE). Each vignette covered five health attributes: maternal health ante partum, time between diagnosis and delivery, process of delivery, maternal outcome, and neonatal outcome. We used feasibility questionnaires, Generalization theory, test-retest reliability and within-group reliability to compare the valuation patterns between groups and methods. We assessed relative weights from each valuation method to test for consistency across groups.
Test-retest reliability was equal across groups, but different across methods: highest for VAS (ICC = 0.61-0.73), intermediate for TTO (ICC = 0.24-0.74) and lowest for DCE (kappa = 0.15-0.37). Within-group reliability was highest in all groups with VAS (ICC = 0.70-0.73), intermediate with DCE (kappa = 0.56-0.76) and lowest with TTO (ICC = 0.20-0.66). Effects of groups were smaller than effects of methods. Differences between groups were largest for severe health states.
Based on our results, decision making among laypersons should use TTO or DCE; patients should use VAS or TTO.
PMCID: PMC3226638  PMID: 22078302
health outcome valuation; preference; vignettes; psychometrics; pregnancy; obstetrics
4.  Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia between 34 and 37 weeks' gestation (HYPITAT-II): a multicentre, open-label randomised controlled trial 
Gestational hypertension (GH) and pre-eclampsia (PE) can result in severe complications such as eclampsia, placental abruption, syndrome of Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) and ultimately even neonatal or maternal death. We recently showed that in women with GH or mild PE at term induction of labour reduces both high risk situations for mothers as well as the caesarean section rate. In view of this knowledge, one can raise the question whether women with severe hypertension, pre-eclampsia or deterioration chronic hypertension between 34 and 37 weeks of gestation should be delivered or monitored expectantly. Induction of labour might prevent maternal complications. However, induction of labour in late pre-term pregnancy might increase neonatal morbidity and mortality compared with delivery at term.
Pregnant women with severe gestational hypertension, mild pre-eclampsia or deteriorating chronic hypertension at a gestational age between 34+0 and 36+6 weeks will be asked to participate in a multi-centre randomised controlled trial. Women will be randomised to either induction of labour or expectant monitoring. In the expectant monitoring arm, women will be induced only when the maternal or fetal condition detoriates or at 37+0 weeks of gestation. The primary outcome measure is a composite endpoint of maternal mortality, severe maternal complications (eclampsia, HELLP syndrome, pulmonary oedema and thromboembolic disease) and progression to severe pre-eclampsia. Secondary outcomes measures are respiratory distress syndrome (RDS), neonatal morbidity and mortality, caesarean section and vaginal instrumental delivery rates, maternal quality of life and costs. Analysis will be intention to treat. The power calculation is based on an expectant reduction of the maternal composite endpoint from 5% to 1% for an expected increase in neonatal RDS from 1% at 37 weeks to 10% at 34 weeks. This implies that 680 women have to be randomised.
This trial will provide insight as to whether in women with hypertensive disorders late pre-term, induction of labour is an effective treatment to prevent severe maternal complications without compromising the neonatal morbidity.
Trial Registration
NTR1792 Clinical trial registration:
PMCID: PMC3161905  PMID: 21736705
5.  Overcoming inherent problems of preference-based techniques for measuring health benefits: An empirical study in the context of kidney transplantation 
Economic valuations of health care programs often require using patients as subjects, implying that research methodology should conform to the surrounding social, cultural and ethical context. The significance of patients' opinions in health care decisions has been well defined but in Greece, and perhaps elsewhere, clinicians remain skeptical. The purpose of this study was to investigate, for the first time in Greece, the feasibility of measuring preference-based health-state utilities and willingness to pay and to determine the context-based adaptations required to overcome inherent elicitation problems.
A survey including a time trade-off (TTO), a standard gamble (SG), and two willingness-to-pay (WTP) questions was self-administered to a homogenous group of 606 end stage renal disease patients in 24 dialysis facilities throughout Greece and the overall response rate was 78.5%. Typical elicitation methods were adapted to overcome methodological problems such as subjective life expectancy and question framing. Spearman's correlation coefficients were calculated between utilities and WTP and parametric tests (independent samples t-test and ANOVA) examined score differences as a result of demographic and clinical factors.
Mean health-state utilities were 72.56 (TTO) and 91.06 (SG) and these were statistically significantly different (P < 0.0005). Significant correlations, in the expected directions, were observed between TTO – SG, TTO – WTP and SG – WTP (P < 0.01). High ceiling effects were observed in the TTO and SG methods indicating patients' adversity to risk and unwillingness to trade-off life years. Higher WTP was observed from younger patients (P < 0.0005), males (P < 0.05), higher education levels (P < 0.01), single (P < 0.0005) and employed (P < 0.005).
This study demonstrated, to a fair extent, that adapting research methods to context-based particularities does not necessarily compromise results and should be considered in situations where standard methods cannot be applied. On the other hand, it is emphasized that the results from this study are preliminary and should be interpreted cautiously until further research demonstrates the practicality, reliability and validity of alternative measurement approaches.
PMCID: PMC1373617  PMID: 16412242
6.  A study of the user's perception of economic value in nursing visits to primary care by the method of contingent valuation 
BMC Family Practice  2011;12:109.
The identification of the attribution of economic value that users of a health system assign to a health service could be useful in planning these services. The method of contingent valuation can provide information about the user's perception of value in monetary terms, and therefore comparable between services of a very different nature. This study attempts to extract the economic value that the subject, user of primary care nursing services in a public health system, attributes to this service by the method of contingent valuation, based on the perspectives of Willingness to Pay (WTP) and Willingness to Accept [Compensation] (WTA).
This is an economic study with a transversal design. The contingent valuation method will be used to estimate the user's willingness to pay (WTP) for the care received from the primary care nurse and the willingness to accept [compensation] (WTA), were this service eliminated. A survey that meets the requisites of the contingent valuation method will be constructed and pilot-tested. Subsequently, 600 interviews will be performed with subjects chosen by systematic randomized sampling from among those who visit nursing at twenty health centers with different socioeconomic characteristics in the Community of Madrid. The characteristics of the subject and of the care received that can explain the variations in WTP, WTA and in the WTP/WTA ratio expressed will be studied. A theoretical validation of contingent valuation will be performed constructing two explanatory multivariate mixed models in which the dependent variable will be WTP, and the WTP/WTA relationship, respectively.
The identification of the attribution of economic value to a health service that does not have a direct price at the time of use, such as a visit to primary care nursing, and the definition of a profile of "loss aversion" in reference to the service evaluated, can be relevant elements in planning, enabling incorporating patient preferences to health policy decision-making.
PMCID: PMC3192666  PMID: 21967306
7.  Costing and Cost Analysis in Randomised Trials: Caveat Emptor 
PharmacoEconomics  2009;27(3):179-188.
The objective of this paper is to provide an overview of the central issues with respect to cost valuation and analysis for a decision maker’s evaluation of costing performed within randomized clinical trials. Costing involves specific choices for valuation and analysis that involve tradeoffs. Understanding these choices and their implications are necessary for proper evaluation of how costs are valued and analyzed within a randomized clinical trial that can not be assessed through a checklist of adherence to general principals..
The most common method of costing, resource costing, involves measuring medical service use in study case report forms and translating this use into a cost by multiplying the number of units of each medical service by price weights for those services. A choice must be made as to how detailed the measurement of resources will be. Micro-costing improves the specificity of the cost estimate, but it is often impractical to precisely measure resources at this level and the price weights for these micro units may not be available. Gross-costing may be more practical and price weights are often easier to find and are more reliable, but important resource differences between treatment groups may be lost in the bundling of resources. Price weights can be either nationally determined or they can be center-specific, but the appropriate price weight will depend on perspective, convenience, completeness, and accuracy. Identifying the resource types and the appropriate price weights for these resources are the essential elements to an accurate valuation of costs.
Once medical services are valued, the resulting individual patient cost estimates must be analyzed. The difference in the average cost between treatment groups is the important summary statistic for cost-effectiveness analysis both from the budgetary and social perspectives. The statistical challenges with cost data typically stem from its skewed distribution and the resulting possibility that the sample mean may be inefficient and possibly inappropriate for statistical inference. Multivariable analysis of cost is useful even if the data come from a randomized trial, but the same distributional problems that affect univariate tests of cost also affect use of cost as a dependent variable in a multivariable regression analysis. The Generalized Linear Model (GLM) overcomes many of the problems of more common cost models, but one must be cautious when applying this model because it is prone to misspecification and precision losses in data with a heavy-tailed log error term.
Attention to the appropriate cost valuation and analysis techniques reviewed here will help bring the same level of rigor and attention to the methodological issues in cost valuation as currently applied to clinical evidence within randomized trials.
PMCID: PMC2971527  PMID: 19354338
8.  Health-state valuations for pertussis: methods for valuing short-term health states 
The incidence of reported adolescent and adult pertussis continues to rise in the United States. Acellular pertussis vaccines for adolescents and adults have been developed and may be available soon for use in the U.S. Our objectives were: (1) to describe patient valuations of pertussis disease and vaccination; and (2) to compare valuations for short-term and long-term health states associated with pertussis.
We conducted telephone surveys with 515 adult patients and parents of adolescent patients with pertussis in Massachusetts to determine valuations of pertussis-related health states for disease and vaccination using time trade-off (TTO) and contingent valuation (CV) techniques. Respondents were randomized to complete either a short-term or long-term TTO exercise. Discrimination between health states for each valuation technique was assessed using Tukey's method, and valuations for short-term vs. long-term health states were compared using the Wilcoxon rank-sum test.
Three hundred three (59%) and 309 (60%) respondents completed and understood the TTO and CV exercises, respectively. Overall, respondents gave lower valuations (lower TTO and higher CV values) to avoid a given state for adolescent/adult disease compared to vaccine adverse events. Infant complications due to pertussis were considered worse than adolescent/adult disease, regardless of the method of valuation. The short-term TTO resulted in lower mean valuations and larger mean differences between health states than the long-term TTO exercise.
Pertussis was considered worse than adverse events due to vaccination. Short-term health-state valuation is better able to discriminate among health states, which is useful for cost-utility analysis.
PMCID: PMC555848  PMID: 15780145
pertussis; time trade-off; willingness-to-pay; short-term health-state
9.  Reconsidering the use of rankings in the valuation of health states: a model for estimating cardinal values from ordinal data 
In survey studies on health-state valuations, ordinal ranking exercises often are used as precursors to other elicitation methods such as the time trade-off (TTO) or standard gamble, but the ranking data have not been used in deriving cardinal valuations. This study reconsiders the role of ordinal ranks in valuing health and introduces a new approach to estimate interval-scaled valuations based on aggregate ranking data.
Analyses were undertaken on data from a previously published general population survey study in the United Kingdom that included rankings and TTO values for hypothetical states described using the EQ-5D classification system. The EQ-5D includes five domains (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) with three possible levels on each. Rank data were analysed using a random utility model, operationalized through conditional logit regression. In the statistical model, probabilities of observed rankings were related to the latent utilities of different health states, modeled as a linear function of EQ-5D domain scores, as in previously reported EQ-5D valuation functions. Predicted valuations based on the conditional logit model were compared to observed TTO values for the 42 states in the study and to predictions based on a model estimated directly from the TTO values. Models were evaluated using the intraclass correlation coefficient (ICC) between predictions and mean observations, and the root mean squared error of predictions at the individual level.
Agreement between predicted valuations from the rank model and observed TTO values was very high, with an ICC of 0.97, only marginally lower than for predictions based on the model estimated directly from TTO values (ICC = 0.99). Individual-level errors were also comparable in the two models, with root mean squared errors of 0.503 and 0.496 for the rank-based and TTO-based predictions, respectively.
Modeling health-state valuations based on ordinal ranks can provide results that are similar to those obtained from more widely analyzed valuation techniques such as the TTO. The information content in aggregate ranking data is not currently exploited to full advantage. The possibility of estimating cardinal valuations from ordinal ranks could also simplify future data collection dramatically and facilitate wider empirical study of health-state valuations in diverse settings and population groups.
PMCID: PMC344742  PMID: 14687419
10.  Measuring consumer preference for models of diabetes care delivered by pharmacists 
Pharmacy Practice  2009;7(4):195-204.
Evaluation of a community pharmacy disease management program for type 2 diabetes, ‘SugarCare’, was conducted. Compared with the standard care offered by pharmacists, this enhanced program offered patients closer monitoring of blood glucose levels, counselling about lifestyle, etc. The SugarCare study was funded by a grant but if the care is to continue some other method of financing must be found.
This study aimed to measure consumer preference for one of the two types of care offered in the SugarCare study, the control/standard and the intervention/enhanced service; the strength of that preference; and participants’ willingness to pay (WTP) for their preferred care.
SugarCare was a parallel groups, control versus intervention, repeated measures design conducted in three areas of NSW, Australia. Patients in the Intervention group (enhanced care) had one initial visit to the pharmacy with six follow up visits over approximately 9 months. At these visits blood glucose was downloaded and patient care issues addressed. At the end of the service, a survey instrument was mailed to the intervention and control participants who were asked to read it and then expect a telephone call within 2 weeks of receipt. Responses were requested over the phone and the survey instrument completed by the researcher. WTP data were collected using a modified payment card method.
Overall, 44/75 (59%; 47%-70% 95%CI) respondents expressed a preference for Scenario B (the enhanced care) while 31/75 (41%; 31%-52% 95%CI) preferred Scenario A (standard care) however, the difference was not statistically significant. The median maximum WTP was AUD10 for the enhanced care and AUD3.50 for the standard care (p<0.03).
While the WTP values expressed were significantly higher for the enhanced care they did not match with the cost providing that diabetes care. Discrete choice analysis has the potential to overcome some of the difficulties encountered with the contingent valuation technique used here. Further research is required before WTP values such as these could be used with confidence to determine funding policy.
PMCID: PMC4134837  PMID: 25136394
Patient Satisfaction; Community Pharmacy Services; Cost-Benefit Analysis; Australia
11.  An exploration of parents’ preferences for foot care in juvenile idiopathic arthritis: a possible role for the discrete choice experiment 
An increased awareness of patients’ and parents’ care preferences regarding foot care is desirable from a clinical perspective as such information may be utilised to optimise care delivery. The aim of this study was to examine parents’ preferences for, and valuations of foot care and foot-related outcomes in juvenile idiopathic arthritis (JIA).
A discrete choice experiment (DCE) incorporating willingness-to-pay (WTP) questions was conducted by surveying 42 parents of children with JIA who were enrolled in a randomised-controlled trial of multidisciplinary foot care at a single UK paediatric rheumatology outpatients department. Attributes explored were: levels of pain; mobility; ability to perform activities of daily living (ADL); waiting time; referral route; and footwear. The DCE was administered at trial baseline. DCE data were analysed using a multinomial-logit-regression model to estimate preferences and relative importance of attributes of foot care. A stated-preference WTP question was presented to estimate parents’ monetary valuation of health and service improvements.
Every attribute in the DCE was statistically significant (p < 0.01) except that of cost (p = 0.118), suggesting that all attributes, except cost, have an impact on parents’ preferences for foot care for their child. The magnitudes of the coefficients indicate that the strength of preference for each attribute was (in descending order): improved ability to perform ADL, reductions in foot pain, improved mobility, improved ability to wear desired footwear, multidisciplinary foot care route, and reduced waiting time. Parents’ estimated mean annual WTP for a multidisciplinary foot care service was £1,119.05.
In terms of foot care service provision for children with JIA, parents appear to prefer improvements in health outcomes over non-health outcomes and service process attributes. Cost was relatively less important than other attributes suggesting that it does not appear to impact on parents’ preferences.
PMCID: PMC3929162  PMID: 24502508
Juvenile idiopathic arthritis; Foot; Discrete choice experiment; Health economics; Podiatry
12.  Individual differences in the use of the response scale determine valuations of hypothetical health states: an empirical study 
The effects of socio-demographic characteristics of the respondent, including age, on valuation scores of hypothetical health states remain inconclusive. Therefore, we analyzed data from a study designed to discriminate between the effects of respondents' age and time preference on valuations of health states to gain insight in the contribution of individual response patterns to the variance in valuation scores.
A total of 212 respondents from three age groups valued the same six hypothetical health states using three different methods: a Visual Analogue Scale (VAS) and two variants of the Time trade-off (TTO). Analyses included a generalizability study, principal components analysis, and cluster analysis.
Valuation scores differed significantly, but not systematically, between valuation methods. A total of 36.8% of variance was explained by health states, 1.6% by the elicitation method, and 0.2% by age group. Individual differences in the use of the response scales (e.g. a tendency to give either high or low TTO scores, or a high or low scoring tendency on the VAS) were the main source of remaining variance. These response patterns were not related to age or other identifiable respondent characteristics.
Individual response patterns in this study were more important determinants of TTO or VAS valuations of health states than age or other respondent characteristics measured. Further valuation research should focus on explaining individual response patterns as a possible key to understanding the determinants of health state valuations.
PMCID: PMC1868724  PMID: 17466068
13.  Keep it simple 
Journal of clinical epidemiology  2008;62(3):296-305.
To examine the relationship between ordinal and cardinal valuation of health states.
Study Design and Setting
We analyzed rank, visual analog scale (VAS), and time trade-off (TTO) responses for 52 health states defined using the EQ-5D classification system developed by the EuroQol Group. We analyzed 179,431 responses from 11,483 subjects in eight countries: Slovenia, Argentina, Denmark, Japan, Netherlands, Spain, United Kingdom, and United States. We first compared responses across methods by frequency of ties and values below dead. Ordinal associations between methods were evaluated using Spearman’s correlation and Kendall’s tau. Next, we estimated numerical values from rank responses using country-specific conditional logit models. After anchoring predicted values on a common scale, we further investigated the cardinal relationships between rank, VAS, and TTO-based values using Pearson’s rho and quadratic regression.
For each country, rank responses are less likely than TTO responses to be tied and to indicate that states are worse than dead. In all countries, rank responses show a strong linear correlation with both TTO (Pearson’s rho = 0.88-0.99) and VAS (rho = 0.91-0.98) responses. However, rank-based values imply greater decrements in health for mild states than cardinal values.
Illiteracy and innumeracy can hinder implementation of complex preference elicitation techniques in diverse settings and populations. These results indicate that ranking exercises may provide an attractive alternative for health-state valuation.
PMCID: PMC2766172  PMID: 18945585
Rank; Quality of life; EQ-5D; Time trade-off; Visual Analog Scale; Ranking
14.  The episodic random utility model unifies time trade-off and discrete choice approaches in health state valuation 
To present an episodic random utility model that unifies time trade-off and discrete choice approaches in health state valuation.
First, we introduce two alternative random utility models (RUMs) for health preferences: the episodic RUM and the more common instant RUM. For the interpretation of time trade-off (TTO) responses, we show that the episodic model implies a coefficient estimator, and the instant model implies a mean slope estimator. Secondly, we demonstrate these estimators and the differences between the estimates for 42 health states using TTO responses from the seminal Measurement and Valuation in Health (MVH) study conducted in the United Kingdom. Mean slopes are estimates with and without Dolan's transformation of worse-than-death (WTD) responses. Finally, we demonstrate an exploded probit estimator, an extension of the coefficient estimator for discrete choice data that accommodates both TTO and rank responses.
By construction, mean slopes are less than or equal to coefficients, because slopes are fractions and, therefore, magnify downward errors in WTD responses. The Dolan transformation of WTD responses causes mean slopes to increase in similarity to coefficient estimates, yet they are not equivalent (i.e., absolute mean difference = 0.179). Unlike mean slopes, coefficient estimates demonstrate strong concordance with rank-based predictions (Lin's rho = 0.91). Combining TTO and rank responses under the exploded probit model improves the identification of health state values, decreasing the average width of confidence intervals from 0.057 to 0.041 compared to TTO only results.
The episodic RUM expands upon the theoretical framework underlying health state valuation and contributes to health econometrics by motivating the selection of coefficient and exploded probit estimators for the analysis of TTO and rank responses. In future MVH surveys, sample size requirements may be reduced through the incorporation of multiple responses under a single estimator.
PMCID: PMC2667164  PMID: 19144115
15.  Prioritising health service innovation investments using public preferences: a discrete choice experiment 
Prioritising scarce resources for investment in innovation by publically funded health systems is unavoidable. Many healthcare systems wish to foster transparency and accountability in the decisions they make by incorporating the public in decision-making processes. This paper presents a unique conceptual approach exploring the public’s preferences for health service innovations by viewing healthcare innovations as ‘bundles’ of characteristics. This decompositional approach allows policy-makers to compare numerous competing health service innovations without repeatedly administering surveys for specific innovation choices.
A Discrete Choice Experiment (DCE) was used to elicit preferences. Individuals chose from presented innovation options that they believe the UK National Health Service (NHS) should invest the most in. Innovations differed according to: (i) target population; (ii) target age; (iii) implementation time; (iv) uncertainty associated with their likely effects; (v) potential health benefits; and, (vi) cost to a taxpayer. This approach fosters multidimensional decision-making, rather than imposing a single decision criterion (e.g., cost, target age) in prioritisation. Choice data was then analysed using scale-adjusted Latent Class models to investigate variability in preferences and scale and valuations amongst respondents.
Three latent classes with considerable heterogeneity in the preferences were present. Each latent class is composed of two consumer subgroups varying in the level of certainty in their choices. All groups preferred scientifically proven innovations, those with potential health benefits that cost less. There were, however, some important differences in their preferences for innovation investment choices: Class-1 (54%) prefers innovations benefitting adults and young people and does not prefer innovations targeting people with ‘drug addiction’ and ‘obesity’. Class- 2 (34%) prefers innovations targeting ‘cancer’ patients only and has negative preferences for innovations targeting elderly, and Class-3 (12%) prefers spending on elderly and cancer patients the most.
DCE can help policy-makers incorporate public preferences for health service innovation investment choices into decision making. The findings provide useful information on the public’s valuation and acceptability of potential health service innovations. Such information can be used to guide innovation prioritisation decisions by comparing competing innovation options. The approach in this paper makes, these often implicit and opaque decisions, more transparent and explicit.
PMCID: PMC4166469  PMID: 25167926
16.  Disproportionate Intrauterine Growth Intervention Trial At Term: DIGITAT 
Around 80% of intrauterine growth restricted (IUGR) infants are born at term. They have an increase in perinatal mortality and morbidity including behavioral problems, minor developmental delay and spastic cerebral palsy. Management is controversial, in particular the decision whether to induce labour or await spontaneous delivery with strict fetal and maternal surveillance. We propose a randomised trial to compare effectiveness, costs and maternal quality of life for induction of labour versus expectant management in women with a suspected IUGR fetus at term.
The proposed trial is a multi-centre randomised study in pregnant women who are suspected on clinical grounds of having an IUGR child at a gestational age between 36+0 and 41+0 weeks. After informed consent women will be randomly allocated to either induction of labour or expectant management with maternal and fetal monitoring. Randomisation will be web-based. The primary outcome measure will be a composite neonatal morbidity and mortality. Secondary outcomes will be severe maternal morbidity, maternal quality of life and costs. Moreover, we aim to assess neurodevelopmental and neurobehavioral outcome at two years as assessed by a postal enquiry (Child Behavioral Check List-CBCL and Ages and Stages Questionnaire-ASQ). Analysis will be by intention to treat. Quality of life analysis and a preference study will also be performed in the same study population. Health technology assessment with an economic analysis is part of this so called Digitat trial (Disproportionate Intrauterine Growth Intervention Trial At Term). The study aims to include 325 patients per arm.
This trial will provide evidence for which strategy is superior in terms of neonatal and maternal morbidity and mortality, costs and maternal quality of life aspects. This will be the first randomised trial for IUGR at term.
Trial registration
Dutch Trial Register and ISRCTN-Register: ISRCTN10363217.
PMCID: PMC1933438  PMID: 17623077
17.  Swedish experience-based value sets for EQ-5D health states 
Quality of Life Research  2013;23(2):431-442.
To estimate Swedish experience-based value sets for EQ-5D health states using general population health survey data.
Approximately 45,000 individuals valued their current health status by means of time trade off (TTO) and visual analogue scale (VAS) methods and answered the EQ-5D questionnaire, making it possible to model the association between the experience-based TTO and VAS values and the EQ-5D dimensions and severity levels. The association between TTO and VAS values and the different severity levels of respondents’ answers on a self-rated health (SRH) question was assessed.
Almost all dimensions (except usual activity) and severity levels had less impact on TTO valuations compared with the UK study based on hypothetical values. Anxiety/depression had the greatest impact on both TTO and VAS values. TTO and VAS values were consistently related to SRH. The inclusion of age, sex, education and socioeconomic group affected the main effect coefficients and the explanatory power modestly.
A value set for EQ-5D health states based on Swedish valuations has been lacking. Several authors have recently advocated the normative standpoint of using experience-based values. Guidelines of economic evaluation for reimbursement decisions in Sweden recommend the use of experience-based values for QALY calculations. Our results that anxiety/depression had the greatest impact on both TTO and VAS values underline the importance of mental health for individuals’ overall HRQoL. Using population surveys is in line with recent thinking on valuing health states and could reduce some of the focusing effects potentially appearing in hypothetical valuation studies.
Electronic supplementary material
The online version of this article (doi:10.1007/s11136-013-0496-4) contains supplementary material, which is available to authorized users.
PMCID: PMC3967073  PMID: 23975375
EQ-5D; Experience-based value set; General population; Self-rated health; Time trade off; Visual analogue scale
18.  Evaluating patient values and preferences for thromboprophylaxis decision making during pregnancy: a study protocol 
Pregnant women with prior venous thromboembolism (VTE) are at risk of recurrence. Low molecular weight heparin (LWMH) reduces the risk of pregnancy-related VTE. LMWH prophylaxis is, however, inconvenient, uncomfortable, costly, medicalizes pregnancy, and may be associated with increased risks of obstetrical bleeding. Further, there is uncertainty in the estimates of both the baseline risk of pregnancy-related recurrent VTE and the effects of antepartum LMWH prophylaxis. The values and treatment preferences of pregnant women, crucial when making recommendations for prophylaxis, are currently unknown. The objective of this study is to address this gap in knowledge.
We will perform a multi-center cross-sectional interview study in Canada, USA, Norway and Finland. The study population will consist of 100 women with a history of lower extremity deep vein thrombosis (DVT) or pulmonary embolism (PE), and who are either pregnant, planning pregnancy, or may in the future consider pregnancy (women between 18 and 45 years). We will exclude individuals who are on full dose anticoagulation or thromboprophylaxis, who have undergone surgical sterilization, or whose partners have undergone vasectomy. We will determine each participant's willingness to receive LMWH prophylaxis during pregnancy through direct choice exercises based on real life and hypothetical scenarios, preference-elicitation using a visual analog scale (“feeling thermometer”), and a probability trade-off exercise. The primary outcome will be the minimum reduction (threshold) in VTE risk at which women change from declining to accepting LMWH prophylaxis. We will explore possible determinants of this choice, including educational attainment, the characteristics of the women’s prior VTE, and prior experience with LMWH. We will determine the utilities that women place on the burden of LMWH prophylaxis, pregnancy-related DVT, pregnancy-related PE and pregnancy-related hemorrhage. We will generate a “personalized decision analysis” using participants’ utilities and their personalized risk of recurrent VTE as inputs to a decision analytic model. We will compare the personalized decision analysis to the participant’s stated choice.
The preferences of pregnant women at risk of VTE with respect to the use of antithrombotic therapy remain unexplored. This research will provide explicit, quantitative expressions of women's valuations of health states related to recurrent VTE and its prevention with LMWH. This information will be crucial for both guideline developers and for clinicians.
PMCID: PMC3495041  PMID: 22646475
19.  Cross-national agreement on disability weights: the European Disability Weights Project 
Disability weights represent the relative severity of disease stages to be incorporated in summary measures of population health. The level of agreement on disability weights in Western European countries was investigated with different valuation methods.
Disability weights for fifteen disease stages were elicited empirically in panels of health care professionals or non-health care professionals with an academic background following a strictly standardised procedure. Three valuation methods were used: a visual analogue scale (VAS); the time trade-off technique (TTO); and the person trade-off technique (PTO). Agreement among England, France, the Netherlands, Spain, and Sweden on the three disability weight sets was analysed by means of an intraclass correlation coefficient (ICC) in the framework of generalisability theory. Agreement among the two types of panels was similarly assessed.
A total of 232 participants were included. Similar rankings of disease stages across countries were found with all valuation methods. The ICC of country agreement on disability weights ranged from 0.56 [95% CI, 0.52–0.62] with PTO to 0.72 [0.70–0.74] with VAS and 0.72 [0.69–0.75] with TTO. The ICC of agreement between health care professionals and non-health care professionals ranged from 0.64 [0.58–0.68] with PTO to 0.73 [0.71–0.75] with VAS and 0.74 [0.72–0.77] with TTO.
Overall, the study supports a reasonably high level of agreement on disability weights in Western European countries with VAS and TTO methods, which focus on individual preferences, but a lower level of agreement with the PTO method, which focuses more on societal values in resource allocation.
PMCID: PMC317384  PMID: 14633276
cross-national comparison; outcome measures; valuation methods; Disability-Adjusted Life Years; Quality-Adjusted Life Years
20.  Estimating the willingness to pay for a quality-adjusted life year in Thailand: does the context of health gain matter? 
This study aims to elicit the value of the willingness to pay (WTP) for a quality-adjusted life year (QALY) and to examine the factors associated with the WTP for a QALY (WTP/QALY) value under the Thai health care setting.
A community-based survey was conducted among 1191 randomly selected respondents. Each respondent was interviewed face-to-face to elicit his/her health state preference in each of three pairs of health conditions: (1) unilateral and bilateral blindness, (2) paraplegia and quadriplegia, and (3) mild and moderate allergies. A visual analog scale (VAS) and time trade off (TTO) were used as the eliciting methods. Subsequently, the respondents were asked about their WTP for the treatment and prevention of each pair of health conditions by using a bidding-game technique.
With regards to treatment, the mean WTP for a QALY value (WTP/QALYtreatment) estimated by the TTO method ranged from 59,000 to 285,000 baht (16.49 baht = US$1 purchasing power parity [PPP]). In contrast, the mean WTP for a QALY value in terms of prevention (WTP/QALYprevention) was significantly lower, ranging from 26,000 to 137,000 baht. Gender, household income, and hypothetical scenarios were also significant factors associated with the WTP/QALY values.
The WTP/QALY values elicited in this study were approximately 0.4 to 2 times Thailand’s 2008 GDP per capita. These values were in line with previous studies conducted in several different settings. This study’s findings clearly support the opinion that a single ceiling threshold should not be used for the resource allocation of all types of interventions.
PMCID: PMC3548562  PMID: 23345984
ceiling threshold; health resource allocation; time trade off; visual analog scale
21.  Willingness to pay for health care services in common cold, retinal detachment, and myocardiac infarction: an internet survey in Japan 
The application of Willingness To Pay (WTP) measurement with Contingent Valuation Method (CVM) to medical services is gradually increasing. Knowing what influences WTP is an important matter because validity of CVM in medical services remains controversial. The objective of this survey is to measure WTP for the treatment of typical acute illnesses and to analyze the factors affecting WTP.
A questionnaire survey was conducted over the Internet, in which 795 men and women between 40 and 59 years old responded to questions about WTP for medical expenses in three hypothetical scenarios: common cold (CC), retinal detachment (RD) and myocardiac infarction (MI).
Mean WTP was $29.9 for CC, $2,233 for RD, and $8,976 for MI. WTP for RD and MI was lower in the low-income group. While WTP for CC did not vary with income, WTP was higher in groups whose current subjective fitness levels were low.
Although WTP measurements are criticized frequently for their validity and reliability, they are still useful for determining the economic value of medical services. Based on the results of this study, it is deemed necessary to enhance safety nets for low-income earners in regards to serious illnesses that incur high medical expenses. Further, it is recommended that the rate of co-payments be set relatively high with respect to mild illnesses for which alternative services are available.
PMCID: PMC1395359  PMID: 16504017
22.  Health State Valuation in Mild to Moderate Cognitive Impairment: Feasibility of Computer-Based, Direct Patient Utility Assessment 
Most patients with dementia will, at some point, need a proxy health care decision maker. It is unknown whether persons with various degrees of cognitive impairment can reliably report their health related preferences.
Cross-sectional and retest study. We performed health state valuations (HSVs) of current and hypothetical future health states on 47 pairs of patients with mild to moderate cognitive impairment and their caregivers using computer-based standard gamble, time trade-off, and rating scale techniques.
Patients’ mean (SD) age was 74.6 (9.3) years. About half of the patients were women (48%) as were most caregivers (73%) who were on average younger (mean age = 66.2 years, SD = 12.2). Most participants were White (83%); 17% were African-American. The mean (SD) Mini-Mental State Examination (MMSE) score of patients was 24.2 (4.6) of 30. All caregivers and 77% of patients (36/47) completed all 18 components of the HSV exercise. Patients who completed the HSV exercise were slightly younger (mean age (SD) = 74.1 (8.5) vs. 75.9 (11.8); p = .569) and had significantly higher MMSE scores (mean score (SD) = 25.0 (4.3) vs. 21.4 (4.4); p = .018). Although MMSE scores below 20 did not preclude the completion of all 18 HSV ratings, being classified as having moderate cognitive impairment was associated with a lower likelihood of completing all scenario ratings (44 % vs. 82%). Patient and caregiver responses showed good consistency across time and across techniques, and were logically consistent.
Obtaining HSVs for current and hypothetical health states was feasible for most patients with mild cognitive impairment and many with moderate cognitive impairment. HSV assessments were consistent and reasonable.
PMCID: PMC3651848  PMID: 18349434
health state valuation; utilities; dementia; cognitive impairment; computer-based techniques; reliability
23.  Willingness to Pay for Hospice Care Using the Contingent Valuation Method 
Yonsei Medical Journal  2011;52(3):510-521.
It is necessary to develop a proper payment system for more health care facilities to provide hospice and palliative cares. In deciding the proper level of payment for hospice per diem fee, willingness to pay (WTP) may provide one of the critical information. This study was conducted to determine WTP for hospice care and to analyze those factors affecting WTP.
Materials and Methods
A contingent valuation method with a double-bounded dichotomous-choice model was used. Interview survey was organized and conducted by a survey company from April 4 to 18, 2008. The mean WTP was calculated through an infinite integration of survival functions.
The average willingness to pay was found to be 42,240 Korean won (KRW) (USD 35), with the amount becoming higher as hospice services were deemed more necessary or where average monthly household income was higher. The amount was also higher among male respondents than females.
To compare this WTP with actual cost (32,500 KRW) (USD 27) for hospice care. To facilitate hospice service, hospice specific payment system should be developed. This study provides information regarding the general public's preference of hospice service and their WTP for hospice care, and it may be useful in the decision-making process.
PMCID: PMC3101053  PMID: 21488196
Hospice; willingness to pay; Per diem payment
24.  Willingness to pay for physician services at a primary contact in Ukraine: results of a contingent valuation study 
The existence of quasi-formal and informal payments in the Ukrainian health care system jeopardizes equity and creates barriers to access to proper care. Patient payment policies that better match patient preferences are necessary. We analyze the potential and feasibility of official patient charges for public health care services in Ukraine by studying the patterns of fee acceptability, ability and willingness to pay (WTP) for public health care among population groups.
We use contingent valuation data collected from 303 respondents representative of the adult Ukrainian population. Three decision points were separated: objection to pay, inability to pay, and level of positive non-zero WTP. These decisions were studied for relations with quality profiles of the services, and socio-demographic characteristics of the respondents and their households.
The likelihood to object to pay is mostly determined by the quality characteristics of the services. Objection to pay is not related to corresponding behavior in real life. The likelihood of being unable to pay is associated with older age, lower income, and a larger share of household members with no income. The level of positive WTP is positively related to income (+7% per 1000 UAH increase in income) and is lower for people who visited a doctor but did not pay (−22%).
Rather substantial WTP levels (between 0.9% and 1.9% of household income) for one visit to physician indicate a potential for official patient charges in Ukraine. User fees may cover a substantial share of personnel cost in the out-patient sector. The patterns of inability to pay support well designed exemption criteria based on age, income, and other aspects of economic status. The WTP patterns highlight the necessity for payments that are proportional to income. Other methodological and policy implications are discussed.
PMCID: PMC3695783  PMID: 23758839
Willingness to pay; Demand; Contingent valuation; Physician services; Ability to pay; Payment acceptance
25.  Assessing willingness to pay for improved sanitation in rural Vietnam 
The willingness to pay (WTP) for the construction of bathrooms with a flush toilet was assessed in households in a rural community in northern Vietnam. We also examined the effects of socio-economic factors on the WTP.
The contingent valuation method, an economic survey technique, was used. We used the iterative bidding game technique to elicit household WTP that involved a sequence of dichotomous choice questions followed by a final open-ended question. A total of 370 households that did not have toilets were selected for this study. Respondents to the questionnaire were the primary income earners and decision-makers of their respective household.
Of those responding to the questionnaire, 62.1 % reported being willing to pay for the construction of bathrooms with a flush toilet. The mean and median of maximum WTP amounts were Viet Nam Dong (VND) 15.6 million and VND 13.0 million, respectively (minimum VND 2.0 million; maximum VND 45.0 million). Significant correlates of the WTP rate were: (1) gender of the head of household, (2) age of the head of household, (3) economic status of household, (4) type of current toilet, (5) satisfaction with existing toilet, and (6) knowledge of health effects of poor sanitation. The significant determinants of WTP amount were (1) geographic location and (2) economic status of household.
About two-third of the households in the study area were willing to pay for an improvement in their current sanitation arrangements. Both WTP rate and WP amount were strongly influenced by the economic status of the households and health knowledge of the study respondents.
PMCID: PMC3709041  PMID: 23143771
Contingent valuation; Willingness to pay; Sanitation; Rural; Vietnam

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