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

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

The Athletic Skills Track: Age- and gender-related normative values of a motor skills test for 4- to 12-year-old children.

OBJECTIVES: The aim of the presented study is to provide age- and gender-related normative values and MQ values for a motor skills test, the Athletic Skills Track, among 4- to 12-year-old children. DESIGN: Cross-sectional. METHODS: In 2016, a total of 7977 Dutch children, 4036 boys (mean age 8.6 years, SD 2.1) and 3941 girls (mean age 8.6 years, SD 2.1), performed an age-related version of the Athletic Skills Track (AST). The AST is a track consisting of 5-7 fundamental movement skill tasks that should be completed as fast as possible. The children performed the test during a regular physical education (PE) lesson under the supervision of their own PE teacher. For each version of the AST (AST-1: n=917; AST-2: n=3947; AST-3: n=3213) age- and gender-related reference centiles were derived from the gathered data using the Lambda, Mu, Sigma (LMS) method. RESULTS: All children completed the AST within 60s (mean 29.6s, SD 7.7). An independent samples t-test showed that boys were significantly faster in completing the track than girls, except for the 4-year-old boys. Therefore, age- and gender-related reference centiles were derived. The reference curves demonstrate an almost linear decrease in time to complete AST-1 and AST-2 with increasing age. CONCLUSIONS: The present study provides age- and gender-related normative values and MQ values for the AST among 4- to 12-year-old Dutch children. With these normative values PE teachers can interpret children's performance on the AST.

Establishing disability weights for congenital pediatric surgical conditions: a multi-modal approach.

BACKGROUND: Burden of disease (BoD) as measured by Disability-Adjusted Life Years (DALYs) is one of the criteria for priority-setting in health care resource allocation. DALYs incorporate disability weights (DWs), which are currently expert-derived estimates or non-existent for most pediatric surgical conditions. The objective of this study is to establish DWs for a subset of key pediatric congenital anomalies using a range of health valuation metrics with caregivers in both high- and low-resource settings. METHOD: We described 15 health states to health professionals (physicians, nurses, social workers, and therapists) and community caregivers in Kenya and Canada. The health states summaries were expert- and community-derived, consisting of a narrated description of the disease and a functional profile described in EQ-5D-5 L style. DWs for each health state were elicited using four health valuation exercises (preference ranking, visual analogue scale (VAS), paired comparison (PC), and time trade-off (TTO)). The PC data were anchored internally to the TTO and externally to existing data to yield DWs for each health state on a scale from 0 (health) to 1 (dead). Any differences in DWs between the two countries were analyzed. RESULTS: In total, 154 participants, matched by profession, were recruited from Kijabe, Kenya (n = 78) and Hamilton, Canada (n = 76). Overall calculated DWs for 15 health states ranged from 0.13 to 0.77, with little difference between countries (intra-class coefficient 0.97). However, DWs generated in Kenya for severe hypospadias and undescended testes were higher than Canadian-derived DWs (p = 0.04 and p < 0.003, respectively). CONCLUSIONS: We have derived country-specific DWs for pediatric congenital anomalies using several low-cost methods and inter-professional and community caregivers. The TTO-anchored PC method appears best suited for future use. The majority of DWs do not appear to differ significantly between the two cultural contexts and could be used to inform further work of estimating the burden of global pediatric surgical disease. Care should be taken in comparing the DWs obtained in the current study to the existent list of DWs because methodological differences may impact on their compatibility.

Patient and physician preferences for oral pharmacotherapy for overactive bladder: two discrete choice experiments.

OBJECTIVE: We examined patient and treating physician (general practitioners, urologists, and [uro]gynecologists) preferences for oral pharmacotherapy (antimuscarinics and beta-3 adrenoceptor agonists) for overactive bladder to gain a deeper understanding of which attributes drive their treatment decision-making and to quantify to what extent. RESEARCH DESIGN AND METHODS: Two separate discrete choice experiments were developed and validated using the input of patients and physicians. The patient experiment contained the following attributes: micturition frequency, incontinence, nocturia, urgency, dry mouth, constipation, increased heart rate, and increased blood pressure. The physician experiment contained two additional attributes: coping and atrial fibrillation. Both were fielded in five European countries. To allow for preference heterogeneity, utility functions were estimated using a mixed multinomial logit model. RESULTS: A total of 442 patient and 318 physician responses were analyzed. Patients ranked the attributes based on their largest potential impact on treatment value as follows: incontinence, nocturia, risk of an increased heart rate, urgency, frequency, risk of increased blood pressure, risk of constipation, and risk of dry mouth; and physicians as follows: incontinence, urgency, nocturia, frequency, risk of dry mouth, coping, risk of increased heart rate, risk of increased blood pressure, risk of atrial fibrillation, and risk of constipation. CONCLUSION AND LIMITATIONS: In their valuations, physicians put more emphasis on increasing benefits, whereas patients put more emphasis on limiting risks of side effects. Another contrast that emerged was that patients' valuations of side effects were found to be fairly insensitive to the presented risk levels (with the exception of risk of dry mouth), whereas physicians' evaluated all side effects in a risk-level dependent manner. The obtained utility functions can be used to predict whether, to what extent, and for which reasons patients and physicians would choose one oral pharmacotherapy over another, as well as to advance shared decision-making.

Balancing equity and efficiency in the Dutch basic benefits package using the principle of proportional shortfall.

Economic evaluations are increasingly used to inform decisions regarding the allocation of scarce health care resources. To systematically incorporate societal preferences into these evaluations, quality-adjusted life year gains could be weighted according to some equity principle, the most suitable of which is a matter of frequent debate. While many countries still struggle with equity concerns for priority setting in health care, the Netherlands has reached a broad consensus to use the concept of proportional shortfall. Our study evaluates the concept and its support in the Dutch health care context. We discuss arguments in the Netherlands for using proportional shortfall and difficulties in transitioning from principle to practice. In doing so, we address universal issues leading to a systematic consideration of equity concerns for priority setting in health care. The article thus has relevance to all countries struggling with the formalization of equity concerns for priority setting.

Criteria for determining a basic health services package. Recent developments in The Netherlands.

The criterion of medical need figures prominently in the Dutch model for reimbursement decisions as well as in many international models for health care priority setting. Nevertheless the conception of need remains too vague and general to be applied successfully in priority decisions. This contribution explores what is wrong with the proposed definitions of medical need and identifies features in the decision-making process that inhibit implementation and usefulness of this criterion. In contrast to what is commonly assumed, the problem is not so much a failure to understand the nature of the medical need criterion and the value judgments involved. Instead the problem seems to be a mismatch between the information regarding medical need and the way in which these concerns are incorporated into policy models. Criteria--medical need, as well as other criteria such as effectiveness and cost-effectiveness--are usually perceived as "hurdles," and each intervention can pass or fail assessment on the basis of each criterion and therefore be included or excluded from public funding. These models fail to understand that choices are not so much between effective and ineffective treatments, or necessary and unnecessary ones. Rather, choices are often between interventions that are somewhat effective and/or needed. Evaluation of such services requires a holistic approach and not a sequence of fail or pass judgments. To improve applicability of criteria that pertain to medical need we therefore suggest further development of these criteria beyond their original binary meaning and propose meaningful ways in which these criteria can be integrated into policy decisions.

Short term and long term health related quality of life after congenital anorectal malformations and congenital diaphragmatic hernia.

AIMS: To examine short term and long term health related quality of life (HRQoL) of survivors of congenital anorectal malformations (ARM) and congenital diaphragmatic hernia (CDH), and to compare these patients' HRQoL with that of the general population. METHODS: HRQoL was measured in 286 ARM patients and 111 CDH patients. All patients were administered a symptom checklist and a generic HRQoL measure. For the youngest children (aged 1-4) the TAIQOL (a preliminary version of the TAPQOL) was used, for the other children (aged 5-15) the TACQOL questionnaire, and for adults (aged >16) the SF-36. RESULTS: As appeared from the symptom checklists, many patients remained symptomatic into adulthood. In the youngest ARM patients (aged 1-4 years), generic HRQoL was severely affected, but the older ARM patients showed better HRQoL. In the CDH patients, the influence of symptoms on HRQoL seemed less profound. The instruments we used revealed little difference between adults treated for ARM or CDH and the general population. CONCLUSIONS: These results show that for two neonatal surgical procedures, improved survival does not come at the expense of poor HRQoL in adults. Even though there is considerable suffering in terms of both morbidity and mortality in the youngest group, the ultimate prognosis of survivors of the two studied congenital malformations is favourable. This finding can be used to reassure parents of patients in need of neonatal surgery for one of these conditions about the prospects for their child.

Diabetic foot ulcers and amputations: estimates of health utility for use in cost-effectiveness analyses of new treatments.

OBJECTIVES: Diabetic foot ulcers (DFU), infections and amputations are associated with high costs of care and loss of health. To evaluate new treatments, both the extra costs incurred and the health utility gained need to be examined. However, evaluations of treatments in diabetes are hampered by the lack of utility values for health states such as DFU. We estimated utility values for health states seen amongst DFU patients. METHODS: We identified 13 unique health states based on presence/type of DFU and amputation. Members of the general public (n=107) received a description of each health state. They were then asked to indicate how undesirable each health state was (using the time trade-off method). Each answer was then transformed to create a value representing the "utility" of the health state, the utility value represented on a 0-1 scale. RESULTS: Valid responses could be obtained from 96 persons. Mean values included: 0.84 (diabetes with no DFU or amputation), 0.75 (uninfected DFU, no amputation), 0.68 (no DFU, previous foot amputation), and 0.63 (uninfected DFU, previous amputation of other foot). The impact of an ulcer depended on amputation status. CONCLUSIONS: Our values correspond with previously published results but are more detailed. In addition, since our values were derived from the general public, economic evaluations that incorporate them will use the generally preferred societal perspective. Therefore, these values are appropriate, practical and sensitive weights to calculate QALYs for cost-effectiveness analyses of foot ulcer treatments.

['Necessity' determined on the basis of disease severity when prioritising health care interventions]. / Ziektelast als uitwerking van het criterium 'noodzakelijkheid' bij het maken van keuzen in de zorg.

In the Netherlands, the Priorities in Healthcare [Keuzen in de Zorg] Committee proposed that the prioritisation of healthcare interventions should in part be based on the criterion 'necessity'. However, this criterion has hardly ever been used. It was proposed that 'necessity' should be defined in terms of disease severity. This concept examines the fraction of expected quality-adjusted life years (QALY) that a patient will lose if the condition concerned is not treated. The following two possible applications for healthcare policy were studied. Firstly, relatively necessary care could be fully reimbursed, whereas less necessary care would only be reimbursed in part. Secondly, for relatively necessary interventions a lower cost-effectiveness threshold (relatively high costs per QALY for necessary care) could be accepted. In these cases the concept of disease severity provides a new feasible interpretation of the criterion 'necessity'.

The cost-effectiveness of neonatal surgery and subsequent treatment for congenital anorectal malformations.

BACKGROUND/PURPOSE: The progress made in all fields of medicine, including neonatal surgery, has contributed to the rise in healthcare costs. Although neonatal surgery may provide survival gains, these could be at the expense of worse quality of life caused by impairment after surgery. For example, congenital anorectal malformations (CAM) are complex anomalies, and the surgical techniques available have their limitations in achieving continence. It therefore seems justifiable to consider what the effects of treatment are in relation to the costs. Evidence of the cost-effectiveness of neonatal surgery, however, is lacking. METHODS: The authors analyzed both direct and indirect, medical and nonmedical costs in patients who had undergone treatment for CAM. Quality-adjusted life years (QALYs) were measured using the EuroQol EQ-5D questionnaire. Descriptive quality-of-life data were collected using a disease-specific questionnaire and a medical consumption questionnaire. RESULTS: Mean costs of treatment are calculated at Euro 31,593. Treated CAM patients suffer stool difficulties and their medical consumption is relatively high. The EQ-5D, however, shows that the quality of life of CAM patients is only slightly lower than that of the general population (0.88 v 0.93). Treatment results in a gain of 12.7 QALYs. Costs per QALY of treatment for CAM amount to Euro 2,482. CONCLUSIONS: Treatment for CAM has a favorable cost-effectiveness ratio compared with other evaluated healthcare programs. Bearing in mind the increasing political interest in evidence-based and cost-effective medicine, the results are encouraging.

Lower urinary tract symptoms suggestive of benign prostatic obstruction--Triumph: health-economical analysis.

Given the ageing of western populations, the cost burden associated with the treatment of LUTS suggestive of BPO will increase substantially over the next few decades. Therefore, from the economic perspective, the primary objective of the Triumph project is the assessment of the cost-effectiveness of treatment options for lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO), formerly referred to as symptomtic benign prostatic hyperplasia (BPH), in medical practice in initially six European countries. All modalities of LUTS treatment used in these countries will be considered. The effectiveness and costs associated with these treatments will be assessed in each country. Data will be gathered from observed medical practice rather than in the setting of a trial. Country-specific aspects will be studied and the outcome of country-specific policies can be predicted. Patient quality of life will also be measured using the I-PSS score as a basis. A number of treatment scenarios will be assessed in terms of both their costs and long-term effects, using a computer simulation. These economic analyses will provide greatly improved insight into the most cost-effective treatments for LUTS suggestive of BPO.

Performance of the EuroQol in children with imperforate anus.

OBJECTIVE: To investigate the feasibility and validity of a proxy version of the EuroQol in children treated for imperforate anus. METHODS: Patients included were between 1 and 51 years of age. Instruments included were the EuroQol, the TACQOL and a disease specific questionnaire, the Langemeijer Stool Questionnaire. Patients older than 15 years filled in all questionnaires themselves, in the age groups 5-10 and 11-15 a parent administered the questionnaires. Feasibility was judged on the number of missing values. In search of validity, EuroQol scores were compared with the prevalence of disease symptoms (convergent validity) and with the TACQOL (construct validity). RESULTS: The number of missings was not related to age. The disease specific questionnaire correlated significantly with the EQvas from 11 years on and with the EQ-5Dindex from 5 years on. The mean correlation between contextual similar domains of the EuroQol and the TACQOL was -0.55. The correlation between different domains was -0.32. CONCLUSION: The results support the idea that the use of a proxy version of the EuroQol is feasible and valid. The convergent validity of the EQvas was supported from 11 years on. The EQ-5D showed good construct and convergent validity from 5 years on.

Cost-effectiveness of neonatal surgery: a review.

BACKGROUND/PURPOSE: Technological developments have revolutionized both diagnosis and treatment in neonatal surgery. However, it has been increasingly recognized that financial resources might become insufficient to provide all the medical care that is technically feasible or that patients and families might desire. The purpose of this study is to apply the theory of health economics to neonatal surgery and to explore the extent and the kind of economic evaluation done in neonatal surgery. METHODS: To explore the work done so far, the authors undertook a literature search aimed at costs and effects of surgical interventions in newborns with Ravitch' surgical index diagnoses of congenital anomalies. Common keywords in cost-effectiveness analysis were used to search Medline. RESULTS: Evidence about the cost effectiveness of neonatal surgery is largely lacking. This is probably because of difficulties in long-term tracking of the patients and to the problem that most generic quality-of-life measures are not applicable in children yet. CONCLUSIONS: Further cost-effectiveness research in neonatal surgery is warranted to settle priority discussions in health care when neonatal surgery is part of such discussions. Methodology for generic quality-of-life measurement in children is badly needed.

Cost utility analysis of sildenafil compared with papaverine-phentolamine injections.

OBJECTIVE: To compare the cost effectiveness of sildenafil and papaverine-phentolamine injections for treating erectile dysfunction. DESIGN: Cost utility analysis comparing treatment with sildenafil (allowing a switch to injection therapy) and treatment with papaverine-phentolamine (no switch allowed). Costs and effects were estimated from the societal perspective. Using time trade-off, a sample of the general public (n=169) valued health states relating to erectile dysfunction. These values were used to estimated health related quality of life by converting the clinical outcomes of a trial into quality adjusted life years (QALYs). PARTICIPANTS: 169 residents of Rotterdam. MAIN OUTCOME MEASURES: Cost per quality adjusted life year. RESULTS: Participants thought that erectile dysfunction limits quality of life considerably: the mean utility gain attributable to sildenafil is 0.11. Overall, treatment with sildenafil gained more QALYs, but the total costs were higher. The incremental cost effectiveness ratio for the introduction of sildenafil was pound sterling 3639 in the first year and fell in following years. Doubling the frequency of use of sildenafil almost doubled the cost per additional QALY. CONCLUSIONS: Treatment with sildenafil is cost effective. When considering funding sildenafil, healthcare systems should take into account that the frequency of use affects cost effectiveness.

Factor XII-dependent fibrinolysis: a double function of plasma kallikrein and the occurrence of a previously undescribed factor XII- and kallikrein-dependent plasminogen proactivator.

Fibrinolytic studies in euglobulin fractions of Fletcher trait plasma (deficient in prekallikrein) revealed reduced activities as compared to normal plasma. A quantitative assay for total plasminogen activator plus proactivator in plasma showed that the amount in Fletcher trait patients is about half of normal (normal = +/- 100 blood activator units [BAU]/ml). Plasma kallikrein partially purified in a high and low molecular weight form exerted plasminogen activator activity amounting to 10-15 BAU/ml plasma. So, the absence of kallikrein in the deficient plasma cannot fully account for the reduction in activator activity. Additions of kallikrein preparations or normal plasma fractions resulted in additional activator activity in Fletcher trait plasma which was assessed at 30-40 BAU/ml. This activity was assumed to originate from a previously undescribed plasminogen proactivator whose activation is kallikrein- and factor XII-dependent. Fractionation experiments demonstrated the presence of two major activities and a minor activity caused by kallikrein in normal plasma. It is concluded that plasma kallikrein has two functions in the generation of factor XII-dependent fibrinolytic activity: one as a direct plasminogen activator and another as a factor in the activation of a major factor XII-dependent plasminogen proactivator.