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1.  Obstetrical outcome valuations by patients, professionals, and laypersons: differences within and between groups using three valuation methods 
Background
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.
Methods
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.
Results
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.
Conclusion
Based on our results, decision making among laypersons should use TTO or DCE; patients should use VAS or TTO.
doi:10.1186/1471-2393-11-93
PMCID: PMC3226638  PMID: 22078302
health outcome valuation; preference; vignettes; psychometrics; pregnancy; obstetrics
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.
Objective
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.
Design
A post hoc analysis of the Hypertension and Pre-eclampsia Intervention Trial At Term (HYPITAT).
Setting
Obstetric departments of six university and 32 teaching and district hospitals in the Netherlands.
Population
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.
Methods
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.
Results
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.
Conclusion
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.
doi:10.1111/j.1471-0528.2012.03405.x
PMCID: PMC3440582  PMID: 22703475
Bishop score; cervical length; expectant management; gestational hypertension; induction of labour; pre-eclampsia
3.  Induction of labour versus expectant monitoring in women with pregnancy induced hypertension or mild preeclampsia at term: the HYPITAT trial 
Background
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.
Methods/Design
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%.
Discussion
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.
doi:10.1186/1471-2393-7-14
PMCID: PMC1950708  PMID: 17662114
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 
Background
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.
Methods/Design
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.
Discussion
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: http://www.trialregister.nl
doi:10.1186/1471-2393-11-50
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 
Background
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.
Methods
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.
Results
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).
Conclusion
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.
doi:10.1186/1472-6963-6-3
PMCID: PMC1373617  PMID: 16412242
6.  Acceptability of willingness to pay techniques to consumers 
Abstract
Objective The purpose of this study was to assess and compare the proportion of usable responses and protest votes obtained with two willingness to pay (WTP) techniques, contingent valuation (CV) and discrete choice experiment (DCE) and to assess the acceptability of the techniques to respondents.
Setting and participants Pregnant women attending the public antenatal clinics of a Sydney teaching hospital were surveyed.
Main variables studied Preference for either Treatment A (artificial rupture of the membranes followed by intravenous oxytocin) or Treatment B (prostaglandin E2 gel followed by oxytocin if necessary) was assessed. Then WTP for the preferred treatments was assessed using CV and WTP for specific attributes of the treatments in the DCE. In addition, the acceptability of the two techniques was compared in terms of responses deemed to be valid according to defined criteria, protest votes and comments recorded by consumers.
Results With the CV, 74% of respondents chose gel and their maximum WTP was Aus$178 compared with $133 for the alternative. A total of 68% of responses were deemed to be valid including 5% who may have been expressing a protest vote. With the DCE, respondents were WTP $55 for every 1 h reduction in the length of time from induction to delivery. A total of 72% of responses were deemed valid and only two of these 258 women were considered to have expressed a protest vote.
Conclusions Only a small number of women expressed objections to the use of WTP questions in health‐care and the majority of women completed both questions successfully.
doi:10.1046/j.1369-6513.2002.00201.x
PMCID: PMC5142733  PMID: 12460223
willingness to pay; discrete choice experiment; contingent valuation; acceptability to consumers; consumer preference
7.  Measurement of consumer preference for treatments used to induce labour: a willingness‐to‐pay approach 
Aim
The purpose of the study was to assess the acceptability to consumers of two methods of induction of labour using a willingness‐to‐pay (WTP) approach. The methods compared were amniotomy plus oxytocin and prostaglandin E2 vaginal gel, followed by oxytocin if necessary.
Methods
A description of each method was presented, in questionnaire format, to pregnant women attending a public hospital ante‐natal clinic. Women were asked to choose one of the two treatments, then give a valuation in dollar terms for both their preferred treatment and the alternative.
Results
It was found that 73.7% of patients preferred gel. The mean maximum WTP for amniotomy plus oxytocin was Aus$133 while that for gel was Aus$178 (P=0.0001). Those who chose amniotomy plus oxytocin were WTP 90% more for their preferred treatment compared with the alternative (Aus$180 vs. Aus$95). Similarly, those who preferred gel were WTP 90% more for their preferred treatment compared with the alternative (Aus$222 vs. Aus$119).
Conclusion
Consumers were able to assess drug information provided on the two therapies, make an informed choice and to value that choice. Information obtained in this way, combined with information on costs, could be used in policy decision‐making.
doi:10.1046/j.1369-6513.2000.00098.x
PMCID: PMC5080968  PMID: 11281930
childbirth; induction of labour; informed choice; Willingness‐to‐pay
8.  Prioritising health service innovation investments using public preferences: a discrete choice experiment 
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1186/1472-6963-14-360
PMCID: PMC4166469  PMID: 25167926
9.  An exploration of parents’ preferences for foot care in juvenile idiopathic arthritis: a possible role for the discrete choice experiment 
Background
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).
Methods
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.
Results
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.
Conclusions
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.
doi:10.1186/1757-1146-7-10
PMCID: PMC3929162  PMID: 24502508
Juvenile idiopathic arthritis; Foot; Discrete choice experiment; Health economics; Podiatry
10.  Health-state valuations for pertussis: methods for valuing short-term health states 
Background
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.
Methods
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.
Results
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.
Conclusion
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.
doi:10.1186/1477-7525-3-17
PMCID: PMC555848  PMID: 15780145
pertussis; time trade-off; willingness-to-pay; short-term health-state
11.  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.
Background
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).
Methods/Design
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.
Discussion
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.
doi:10.1186/1471-2296-12-109
PMCID: PMC3192666  PMID: 21967306
12.  The Individual Health Discount Rate in Patients with Ulcerative Colitis 
Inflammatory bowel diseases  2010;17(6):1328-1332.
Background
In cost-effectiveness analysis, discount rates are used in calculating the value of future costs and benefits. However, standard discount rates may not accurately describe the decision-making of patients with Ulcerative Colitis (UC). These patients often choose the long-term risks of immunosuppressive therapy over the short-term risks of colectomy, demonstrating very high discount rates for future health. In this study, we aimed to measure the discount rate in UC patients and identify variables associated with the discount rate.
Methods
We surveyed patients with UC and patients who were post-colectomy for UC to measure their valuations of UC and colectomy health states. We used Standard Gamble(SG) and Time-Trade-Off(TTO) methods to assess current and future health state valuations, and calculated the discount rate.
Results
Participants included 150 subjects with UC and 150 subjects who were post-colectomy for UC. Discount rates varied widely (20.6%–100%) with an overall median rate of 55.0%, which was significantly higher than the standard rate of 5%. Older age and male gender and predicted high discount rates (aversion to immediate risk in favor of distant future risk). For each additional decade of age, patients’ expected discount rate increased by 0.77%. Female gender was the only predictor of very low discount rates. Female patients’ discount rates averaged 8.1% less than age-matched males.
Conclusions
The accepted discount rate of 5% grossly underestimates UC patients’ preference for long-term over short-term risk. This might explain UC patients’ frequent choice of the long-term risks of immunosuppressive medical therapy over the short-term risks of colectomy.
doi:10.1002/ibd.21515
PMCID: PMC4813665  PMID: 21560195
Ulcerative Colitis; Discount Rates; Quality of Life; utilities
13.  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
14.  A Systematic Review of Studies Eliciting Willingness-to-Pay per Quality-Adjusted Life Year: Does It Justify CE Threshold? 
PLoS ONE  2015;10(4):e0122760.
Background
A number of studies have been conducted to estimate willingness to pay (WTP) per quality-adjusted life years (QALY) in patients or general population for various diseases. However, there has not been any systematic review summarizing the relationship between WTP per QALY and cost-effectiveness (CE) threshold based on World Health Organization (WHO) recommendation.
Objective
To systematically review willingness-to-pay per quality-adjusted-life-year (WTP per QALY) literature, to compare WTP per QALY with Cost-effectiveness (CE) threshold recommended by WHO, and to determine potential influencing factors.
Methods
We searched MEDLINE, EMBASE, Psyinfo, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Center of Research Dissemination (CRD), and EconLit from inception through 15 July 2014. To be included, studies have to estimate WTP per QALY in health-related issues using stated preference method. Two investigators independently reviewed each abstract, completed full-text reviews, and extracted information for included studies. We compared WTP per QALY to GDP per capita, analyzed, and summarized potential influencing factors.
Results
Out of 3,914 articles founded, 14 studies were included. Most studies (92.85%) used contingent valuation method, while only one study used discrete choice experiments. Sample size varied from 104 to 21,896 persons. The ratio between WTP per QALY and GDP per capita varied widely from 0.05 to 5.40, depending on scenario outcomes (e.g., whether it extended/saved life or improved quality of life), severity of hypothetical scenarios, duration of scenario, and source of funding. The average ratio of WTP per QALY and GDP per capita for extending life or saving life (2.03) was significantly higher than the average for improving quality of life (0.59) with the mean difference of 1.43 (95% CI, 1.81 to 1.06).
Conclusion
This systematic review provides an overview summary of all studies estimating WTP per QALY studies. The variation of ratio of WTP per QALY and GDP per capita depended on several factors may prompt discussions on the CE threshold policy. Our research work provides a foundation for defining future direction of decision criteria for an evidence-informed decision making system.
doi:10.1371/journal.pone.0122760
PMCID: PMC4391853  PMID: 25855971
15.  Validity of Willingness to Pay Measures under Preference Uncertainty 
PLoS ONE  2016;11(4):e0154078.
Recent studies in the marketing literature developed a new method for eliciting willingness to pay (WTP) with an open-ended elicitation format: the Range-WTP method. In contrast to the traditional approach of eliciting WTP as a single value (Point-WTP), Range-WTP explicitly allows for preference uncertainty in responses. The aim of this paper is to apply Range-WTP to the domain of contingent valuation and to test for its theoretical validity and robustness in comparison to the Point-WTP. Using data from two novel large-scale surveys on the perception of solar radiation management (SRM), a little-known technique for counteracting climate change, we compare the performance of both methods in the field. In addition to the theoretical validity (i.e. the degree to which WTP values are consistent with theoretical expectations), we analyse the test-retest reliability and stability of our results over time. Our evidence suggests that the Range-WTP method clearly outperforms the Point-WTP method.
doi:10.1371/journal.pone.0154078
PMCID: PMC4838267  PMID: 27096163
16.  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.
Objectives:
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.
Methods:
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.
Results:
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).
Conclusions:
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
17.  EuroQol Protocols for Time Trade-Off Valuation of Health Outcomes 
Pharmacoeconomics  2016;34(10):993-1004.
The time trade-off (TTO) valuation technique is widely used to determine utility values of health outcomes to inform quality-adjusted life-year (QALY) calculations for use in economic evaluation. Protocols for implementing TTO vary in aspects such as the trade-off framework, iteration procedure and its administration model and method, training of respondents and interviewers, and quality control of data collection. The most widely studied and utilized TTO valuation protocols are the Measurement and Valuation of Health (MVH) protocol, the Paris protocol and the EuroQol Valuation Technology (EQ-VT) protocol, all developed by members of the EuroQol Group. The MVH protocol and its successor, the Paris protocol, were developed for valuation of EQ-5D-3L health states. Both protocols were designed for a trained interviewer to elicit preferences from a respondent using the conventional TTO framework with a fixed time horizon of 10 years and an iteration procedure combining bisection and titration. Developed for valuation of EQ-5D-5L health states, the EQ-VT protocol adopted a composite TTO framework and made use of computer technology to facilitate data collection. Training and monitoring of interviewers and respondents is a pivotal component of the EQ-VT protocol. Research is underway aiming to further improve the EuroQol protocols, which form an important basis for the current practice of health technology assessment in many countries.
doi:10.1007/s40273-016-0404-1
PMCID: PMC5023738  PMID: 27084198
18.  Disproportionate Intrauterine Growth Intervention Trial At Term: DIGITAT 
Background
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.
Methods/design
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.
Discussion
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.
doi:10.1186/1471-2393-7-12
PMCID: PMC1933438  PMID: 17623077
19.  The influence of age on health valuations: the older olds prefer functional independence while the younger olds prefer less morbidity 
Clinical Interventions in Aging  2015;10:1131-1139.
Background
To assess the effectiveness of geriatric interventions, The Older Persons and Informal Caregivers Survey – Composite Endpoint (TOPICS-CEP) has been developed based on health valuations of older persons and informal caregivers. This study explored the influence of the raters’ age on the preference weights of TOPICS-CEP’s components.
Methods
A vignette study was conducted with 200 raters (mean age ± standard deviation: 72.5±11.8 years; 66.5% female). Profiles of older persons were used to obtain the preference weights for all TOPICS-CEP components: morbidity, functional limitations, emotional well-being, pain experience, cognitive functioning, social functioning, self-perceived health, and self-perceived quality of life. The raters assessed the general wellbeing of these vignettes on a 0–10 scale. Mixed linear regression analysis with interaction terms was used to explore the effects of raters’ age on the preference weights.
Results
Interaction effects between age and the TOPICS-CEP components showed that older raters gave significantly (P<0.05) more weight to functional limitations and social functioning and less to morbidities and pain experience, compared to younger raters.
Conclusion
Researchers examining effectiveness in elderly care need to consider the discrepancies between health valuations of younger olds and older olds when selecting or establishing outcome measures. In clinical decision making, health care professionals need to be aware of this discrepancy as well. For this reason we highly recommend shared decision making in geriatric care.
doi:10.2147/CIA.S78698
PMCID: PMC4501683  PMID: 26185432
general wellbeing; preferences; valuation; domains; composite endpoint; age
20.  Irrational decision-making in an amoeboid organism: transitivity and context-dependent preferences 
Most models of animal foraging and consumer choice assume that individuals make choices based on the absolute value of items and are therefore ‘economically rational’. However, frequent violations of rationality by animals, including humans, suggest that animals use comparative valuation rules. Are comparative valuation strategies a consequence of the way brains process information, or are they an intrinsic feature of biological decision-making? Here, we examine the principles of rationality in an organism with radically different information-processing mechanisms: the brainless, unicellular, slime mould Physarum polycephalum. We offered P. polycephalum amoebas a choice between food options that varied in food quality and light exposure (P. polycephalum is photophobic). The use of an absolute valuation rule will lead to two properties: transitivity and independence of irrelevant alternatives (IIA). Transitivity is satisfied if preferences have a consistent, linear ordering, while IIA states that a decision maker's preference for an item should not change if the choice set is expanded. A violation of either of these principles suggests the use of comparative rather than absolute valuation rules. Physarum polycephalum satisfied transitivity by having linear preference rankings. However, P. polycephalum's preference for a focal alternative increased when a third, inferior quality option was added to the choice set, thus violating IIA and suggesting the use of a comparative valuation process. The discovery of comparative valuation rules in a unicellular organism suggests that comparative valuation rules are ubiquitous, if not universal, among biological decision makers.
doi:10.1098/rspb.2010.1045
PMCID: PMC3013386  PMID: 20702460
rationality; slime moulds; foraging; content-dependent; transitivity; independence of irrelevant alternatives
21.  Eliciting preferences for priority setting in genetic testing: a pilot study comparing best-worst scaling and discrete-choice experiments 
European Journal of Human Genetics  2013;21(11):1202-1208.
Given the increasing number of genetic tests available, decisions have to be made on how to allocate limited health-care resources to them. Different criteria have been proposed to guide priority setting. However, their relative importance is unclear. Discrete-choice experiments (DCEs) and best-worst scaling experiments (BWSs) are methods used to identify and weight various criteria that influence orders of priority. This study tests whether these preference eliciting techniques can be used for prioritising genetic tests and compares the empirical findings resulting from these two approaches. Pilot DCE and BWS questionnaires were developed for the same criteria: prevalence, severity, clinical utility, alternatives to genetic testing available, infrastructure for testing and care established, and urgency of care. Interview-style experiments were carried out among different genetics professionals (mainly clinical geneticists, researchers and biologists). A total of 31 respondents completed the DCE and 26 completed the BWS experiment. Weights for the levels of the six attributes were estimated by conditional logit models. Although the results derived from the DCE and BWS experiments differed in detail, we found similar valuation patterns in the DCE and BWS experiments. The respondents attached greatest value to tests with high clinical utility (defined by the availability of treatments that reduce mortality and morbidity) and to testing for highly prevalent conditions. The findings from this study exemplify how decision makers can use quantitative preference eliciting methods to measure aggregated preferences in order to prioritise alternative clinical interventions. Further research is necessary to confirm the survey results.
doi:10.1038/ejhg.2013.36
PMCID: PMC3798841  PMID: 23486538
resource allocation; priority setting; discrete-choice experiment; best-worst scaling; genetic testing
22.  How prior preferences determine decision-making frames and biases in the human brain 
eLife  null;5:e20317.
Understanding how option values are compared when making a choice is a key objective for decision neuroscience. In natural situations, agents may have a priori on their preferences that create default policies and shape the neural comparison process. We asked participants to make choices between items belonging to different categories (e.g., jazz vs. rock music). Behavioral data confirmed that the items taken from the preferred category were chosen more often and more rapidly, which qualified them as default options. FMRI data showed that baseline activity in classical brain valuation regions, such as the ventromedial Prefrontal Cortex (vmPFC), reflected the strength of prior preferences. In addition, evoked activity in the same regions scaled with the default option value, irrespective of the eventual choice. We therefore suggest that in the brain valuation system, choices are framed as comparisons between default and alternative options, which might save some resource but induce a decision bias.
DOI: http://dx.doi.org/10.7554/eLife.20317.001
eLife digest
If you had the choice of listening to a piece of music by either the singer Céline Dion or jazz pianist Keith Jarrett, which would you pick? When choosing between two mutually exclusive options, the brain first assigns a value to each. An area called the ventromedial prefrontal cortex (vmPFC) compares these two values and calculates the difference between them. The vmPFC then relays this difference to other brain regions that trigger the movements required to obtain the selected option.
But what exactly is the vmPFC comparing? A reasonable assumption is that we approach the decision with an existing preference for one of the options based on our previous experience. Lopez-Persem et al. set out to determine whether and how the vmPFC uses this existing preference – for example, for pop music over jazz – to drive the decision-making process.
For the experiments, volunteers were asked to rate how much they liked individual musicians spanning a range of different genres. While lying inside a brain scanner, the subjects then had to choose their favorite from pairs of musicians selected from the list. When making such decisions, volunteers must consider both the overall category (do I prefer jazz or pop?) but also the individual examples (a pop music fan might choose jazz if the pop option is Britney Spears). Lopez-Persem et al. found that the volunteer’s decisions were biased towards their prior preference. Pop music fans chose Céline Dion or Britney Spears more often than would be expected based on the likability ratings they had given the individual artists in the study.
Brain imaging revealed that the vmPFC represents choices as ‘default minus alternative’, where the default is any member of the previously preferred category (e.g. any pop artist for a pop music fan) and the alternative is from a different category (e.g. a jazz artist). Baseline vmPFC activity is higher for members of the preferred category, giving these options a head start over the alternatives. Asking volunteers to choose between other types of objects, including food and magazines, produced similar results. The brain thus uses a general strategy for decision-making that saves time and effort, but which also introduces bias. The next step is to work out how downstream brain regions use the vmPFC signal to select the preferred option.
DOI: http://dx.doi.org/10.7554/eLife.20317.002
doi:10.7554/eLife.20317
PMCID: PMC5132340  PMID: 27864918
decision-making; neuroeconomics; default bias; fMRI; brain valuation system; ventromedial prefrontal cortex; Human
23.  Reconsidering the use of rankings in the valuation of health states: a model for estimating cardinal values from ordinal data 
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1186/1478-7954-1-12
PMCID: PMC344742  PMID: 14687419
24.  Keep it simple 
Journal of clinical epidemiology  2008;62(3):296-305.
Objectives
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.
Results
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.
Conclusions
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.
doi:10.1016/j.jclinepi.2008.07.002
PMCID: PMC2766172  PMID: 18945585
Rank; Quality of life; EQ-5D; Time trade-off; Visual Analog Scale; Ranking
25.  Multiple Sclerosis Patients Valuing Their Own Health Status: Valuation and Psychometric Properties of the 15D 
Neurology International  2016;8(3):6416.
An ongoing debate on decision and cost-utility analyses is whether to use preferences of general public or patients. The aim of this study was to replicate the valuation procedure of the multi-attribute utility generic measure, 15D, using a sample of multiple sclerosis (MS) patients and to assess its psychometric properties. Consecutive outpatient MS patients were recruited from two MS centers in Greece. The three-stage valuation procedure was applied and, with the use of elicited preference weights, an MS patients’ algorithm was developed. The original Finnish value set derived from healthy individuals was also used to calculate scores and a comparison between the two algorithms was made. A total of 64 MS patients were evaluated. The 15D scores obtained with the MS patients’ valuation algorithm were higher than the original one. The derived utilities differed significantly with respect to age, depressive symptoms, Expanded Disability Status Scale score and clinical form. MS patients indicated as most important domains mobility, mental functioning and vitality. Cronbach’s alpha was estimated 0.876 and correlations between relevant dimensions of the instruments were moderate to high. The 15D was generally feasible and reliable in patients with MS and the valuation system yielded acceptable psychometric properties.
doi:10.4081/ni.2016.6416
PMCID: PMC5066103  PMID: 27761225
Multiple sclerosis; 15D; Valuation; utilities; Health-related quality of life

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