How to Present a Decision Object in Health Preference Research: Attributes and Levels, the Decision Model, and the Descriptive Framework.

In health preference research (HPR) studies, data are generated by participants'/subjects' decisions. When developing an HPR study, it is therefore important to have a clear understanding of the components of a decision and how those components stimulate participant behavior. To obtain valid and reliable results, study designers must sufficiently describe the decision model and its components. HPR studies require a detailed examination of the decision criteria, detailed documentation of the descriptive framework, and specification of hypotheses. The objects that stimulate subjects' decisions in HPR studies are defined by attributes and attribute levels. Any limitations in the identification and presentation of attributes and levels can negatively affect preference elicitation, the quality of the HPR data, and study results. This practical guide shows how to link the HPR question to an underlying decision model. It covers how to (1) construct a descriptive framework that presents relevant characteristics of a decision object and (2) specify the research hypotheses. The paper outlines steps and available methods to achieve all this, including the methods' advantages and limitations.

Digital thErapy For Improved tiNnitus carE Study (DEFINE): Protocol for a randomised controlled trial.

Tinnitus is a common health condition, affecting approximately 15% of the UK population. The tinnitus treatment with the strongest evidence base is Cognitive Behavioural Therapy (CBT), with standard tinnitus therapy typically augmented with education, relaxation and other techniques. Availability of CBT and conventional tinnitus therapy more broadly is limited for tinnitus sufferers. The DEFINE trial aims to assess whether smartphone-delivered tinnitus therapy, the Oto app, is as effective as current standard care, one-to-one therapist-delivered tinnitus treatment for the treatment of tinnitus in adults. The trial is registered in the ISRCTN Registry: ISRCTN99577932. DEFINE is an open-label, non-inferiority, prospective, parallel design, randomised-controlled trial. Recruitment, interventions and assessments will be remote, enabling UK-wide participant involvement. 198 participants aged 18 years or more will be recruited via social media advertisement or via primary care physicians. A screening process will identify those with tinnitus that impacts health-related quality of life, and following consent smartphone-based audiometry will be performed. Randomisation 1:1 to the Oto app or one-to-one therapist-led tinnitus therapy will be performed centrally by computer, matching groups for age, sex and hearing level. Following participant allocation, the Oto app will be provided for immediate use, or a one-to-one remote therapy appointment booked to occur within approximately 1 week, with up to 6 sessions delivered. Participant outcomes will be collected at 4,12, 26 and 52 weeks via questionnaire and phone call. The primary outcome is the change in Tinnitus Functional Index (TFI) total score measured at 26 weeks following allocation. Adverse events will be recorded. A health economic evaluation in the form of a cost-utility analysis will be performed using data from participant submitted EuroQol 5D-5L and Health Utilities Index Mark 3 scores and resource use data. Trial results will be made publicly available, including a plain English summary.

Detection and Control of Pregnancy Hypertension Using Self-Monitoring of Blood Pressure With Automated Telemonitoring: Cost Analyses of the BUMP Randomized Trials.

BACKGROUND: Pregnancy hypertension continues to cause maternal and perinatal morbidity. Two linked UK randomized trials showed adding self-monitoring of blood pressure (SMBP) with automated telemonitoring to usual antenatal care did not result in earlier detection or better control of pregnancy hypertension. This article reports the trials' integrated cost analyses. METHODS: Two cost analyses. SMBP with usual care was compared with usual care alone in pregnant individuals at risk of hypertension (BUMP 1 trial [Blood Pressure Monitoring in High Risk Pregnancy to Improve the Detection and Monitoring of Hypertension], n=2441) and with hypertension (BUMP 2 trial, n=850). Clinical notes review identified participant-level antenatal, intrapartum, and postnatal care and these were costed. Comparisons between trial arms used means and 95% CIs. Within BUMP 2, chronic and gestational hypertension cohorts were analyzed separately. Telemonitoring system costs were reported separately. RESULTS: In BUMP 1, mean (SE) total costs with SMBP and with usual care were £7200 (£323) and £7063 (£245), respectively, mean difference (95% CI), £151 (-£633 to £936). For the BUMP 2 chronic hypertension cohort, corresponding figures were £13 384 (£1230), £12 614 (£1081), mean difference £323 (-£2904 to £3549) and for the gestational hypertension cohort were £11 456 (£901), £11 145 (£959), mean difference £41 (-£2486 to £2567). The per-person cost of telemonitoring was £6 in BUMP 1 and £29 in BUMP 2. CONCLUSIONS: SMBP was not associated with changes in the cost of health care contacts for individuals at risk of, or with, pregnancy hypertension. This is reassuring as SMBP in pregnancy is widely prevalent, particularly because of the COVID-19 pandemic. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03334149.

Long-term healthcare utilization and costs of babies born after assisted reproductive technologies (ART): a record linkage study with 10-years' follow-up in England.

STUDY QUESTION: Is the long-term health care utilization of children born after ART more costly to the healthcare system in England than children born to mothers with no fertility problems? SUMMARY ANSWER: Children born after ART had significantly more general practitioner (GP) consultations and higher primary care costs up to 10 years after birth, and significantly higher hospital admission costs in the first year after birth, compared to children born to mothers with no fertility problems. WHAT IS KNOWN ALREADY: There is evidence that children born after ART are at an increased risk of adverse birth outcomes and a small increased risk of rare adverse outcomes in childhood. STUDY DESIGN, SIZE, DURATION: We conducted a longitudinal study of 368 088 mother and baby pairs in England using a bespoke linked dataset. Singleton babies born 1997-2018, and their mothers, who were registered at GP practices in England contributing data to the Clinical Practice Research Datalink (CPRD), were identified through the CPRD GOLD mother-baby dataset; this data was augmented with further linkage to the mothers' Human Fertilisation and Embryology Authority (HFEA) Register data. Four groups of babies were identified through the mothers' records: a 'fertile' comparison group, an 'untreated sub-fertile' group, an 'ovulation induction' group, and an ART group. Babies were followed-up from birth to 28 February 2021, unless censored due to loss to follow-up (e.g. leaving GP practice, emigration) or death. PARTICIPANTS/MATERIALS, SETTING, METHODS: The CPRD collects anonymized coded patient electronic health records from a network of GPs in the UK. We estimated primary care costs and hospital admission costs for babies in the four fertility groups using the CPRD GOLD data and the linked Hospital Episode Statistics (HES) Admitted Patient Care (APC) data. Linear regression was used to compare the care costs in the different groups. Inverse probability weights were generated and applied to adjust for potential bias caused by attrition due to loss to follow-up. MAIN RESULTS AND THE ROLE OF CHANCE: Children born to mothers with no fertility problems had significantly fewer consultations and lower primary care costs compared to the other groups throughout the 10-years' follow up. Regarding hospital costs, children born after ART had significantly higher hospital admission costs in the first year after birth compared to those born to mothers with no fertility problems (difference = £307 (95% CI: 153, 477)). The same pattern was observed in children born after untreated subfertility and ovulation induction. LIMITATIONS, REASONS FOR CAUTION: HFEA linkage uses non-donor data cycles only, and the introduction of consent for data use reduced the availability of HFEA records after 2009. The fertility groups were derived by augmenting HFEA data with evidence from primary care records; however, there remains some potential misclassification of exposure groups. The cost of neonatal critical care is not captured in the HES APC data, which may cause underestimation of the cost differences between the comparison group and the infertility groups. WIDER IMPLICATIONS OF THE FINDINGS: The findings can help anticipate the financial impact on the healthcare system associated with subfertility and ART, particularly as the demand for these treatments grows. STUDY FUNDING/COMPETING INTEREST(S): C.C. and this work were funded by a UK Medical Research Council Career Development Award [MR/L019671/1] and a UK MRC Transition Support Award [MR/W029286/1]. X.H. is an Australia National Health and Medical Research Council (NHMRC) Emerging Leadership Fellow [grant number 2009253]. The authors declare no competing interest. TRIAL REGISTRATION NUMBER: N/A.

Frenotomy with breastfeeding support versus breastfeeding support alone for infants with tongue-tie and breastfeeding difficulties: the FROSTTIE RCT.

Background: Tongue-tie can be diagnosed in 3-11% of babies, with some studies reporting almost universal breastfeeding difficulties, and others reporting very few feeding difficulties that relate to the tongue-tie itself, instead noting that incorrect positioning and attachment are the primary reasons behind the observed breastfeeding difficulties and not the tongue-tie itself. The only existing trials of frenotomy are small and underpowered and/or include only very short-term or subjective outcomes. Objective: To investigate whether frenotomy is clinically and cost-effective to promote continuation of breastfeeding at 3 months in infants with breastfeeding difficulties diagnosed with tongue-tie. Design: A multicentre, unblinded, randomised, parallel group controlled trial. Setting: Twelve infant feeding services in the UK. Participants: Infants aged up to 10 weeks referred to an infant feeding service (by a parent, midwife or other breastfeeding support service) with breastfeeding difficulties and judged to have tongue-tie. Interventions: Infants were randomly allocated to frenotomy with standard breastfeeding support or standard breastfeeding support without frenotomy. Main outcome measures: Primary outcome was any breastmilk feeding at 3 months according to maternal self-report. Secondary outcomes included mother's pain, exclusive breastmilk feeding, exclusive direct breastfeeding, frenotomy, adverse events, maternal anxiety and depression, maternal and infant NHS health-care resource use, cost-effectiveness, and any breastmilk feeding at 6 months of age. Results: Between March 2019 and November 2020, 169 infants were randomised, 80 to the frenotomy with breastfeeding support arm and 89 to the breastfeeding support arm from a planned sample size of 870 infants. The trial was stopped in the context of the COVID-19 pandemic due to withdrawal of breastfeeding support services, slow recruitment and crossover between arms. In the frenotomy with breastfeeding support arm 74/80 infants (93%) received their allocated intervention, compared to 23/89 (26%) in the breastfeeding support arm. Primary outcome data were available for 163/169 infants (96%). There was no evidence of a difference between the arms in the rate of breastmilk feeding at 3 months, which was high in both groups (67/76, 88% vs. 75/87, 86%; adjusted risk ratio 1.02, 95% confidence interval 0.90 to 1.16). Adverse events were reported for three infants after surgery [bleeding (n = 1), salivary duct damage (n = 1), accidental cut to the tongue and salivary duct damage (n = 1)]. Cost-effectiveness could not be determined with the information available. Limitations: The statistical power of the analysis was extremely limited due to not achieving the target sample size and the high proportion of infants in the breastfeeding support arm who underwent frenotomy. Conclusions: This trial does not provide sufficient information to assess whether frenotomy in addition to breastfeeding support improves breastfeeding rates in infants diagnosed with tongue-tie. Future work: There is a clear lack of equipoise in the UK concerning the use of frenotomy, however, the effectiveness and cost-effectiveness of the procedure still need to be established. Other study designs will need to be considered to address this objective. Trial registration: This trial is registered as ISRCTN 10268851. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment Programme (project number 16/143/01) and will be published in full in Health Technology Assessment; Vol. 27, No. 11. See the NIHR Journals Library website for further project information. The funder had no role in study design or data collection, analysis and interpretation. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

Many mothers and babies experience difficulties in establishing breastfeeding. In some babies it is thought that their difficulties may be linked to a condition called tongue-tie, in which a piece of skin tightly joins the middle part of the underside of the tongue to the base of the baby's mouth. This can be treated by an operation to divide the tight part/skin in the middle of the underneath of the tongue. We planned to carry out a trial of 870 babies to find out whether an operation together with breastfeeding support helps more mothers and babies with tongue-tie to continue breastfeeding until the baby is 3 months old compared to breastfeeding support on its own and whether the costs were different between the two groups of mothers and babies. We were only able to recruit 169 babies as the trial was stopped because of slow recruitment, changes to services in the COVID-19 pandemic and a high proportion of the babies in the breastfeeding support group going on to have an operation. There were no differences in the rate of breastfeeding at 3 months between the babies in the group who had an operation straightaway and those in the group that had breastfeeding support alone, or had an operation later. More than four in every five babies in both groups were still breastmilk feeding at 3 months. Three babies who had an operation, around 1 in 50 babies, had a complication of the operation (bleeding, scarring or a cut to the tube that makes saliva). Because of the small size of the study, we cannot say whether an operation to divide a tongue-tie along with breastfeeding support helps babies with tongue-tie and breastfeeding difficulties or has different costs. We will need to try different types of research to answer the question.

Neonatal health care costs of very preterm babies in England: a retrospective analysis of a national birth cohort.

OBJECTIVES: Babies born between 27+0 and 31+6 weeks of gestation represent the largest group of very preterm babies requiring National Health Service (NHS) care; however, up-to-date, cost figures for the UK are not currently available. This study estimates neonatal costs to hospital discharge for this group of very preterm babies in England. DESIGN: Retrospective analysis of resource use data recorded within the National Neonatal Research Database. SETTING: Neonatal units in England. PATIENTS: Babies born between 27+0 and 31+6 weeks of gestation in England and discharged from a neonatal unit between 2014 and 2018. MAIN OUTCOME MEASURES: Days receiving different levels of neonatal care were costed, along with other specialised clinical activities. Mean resource use and costs per baby are presented by gestational age at birth, along with total costs for the cohort. RESULTS: Based on data for 28 154 very preterm babies, the annual total costs of neonatal care were estimated to be £262 million, with 96% of costs attributable to routine daily care provided by units. The mean (SD) total cost per baby of this routine care varied by gestational age at birth; £75 594 (£34 874) at 27 weeks as compared with £27 401 (£14 947) at 31 weeks. CONCLUSIONS: Neonatal healthcare costs for very preterm babies vary substantially by gestational age at birth. The findings presented here are a useful resource to stakeholders including NHS managers, clinicians, researchers and policymakers.

Gestational age and hospital admission costs from birth to childhood: a population-based record linkage study in England.

OBJECTIVE: To examine the association between gestational age at birth and hospital admission costs from birth to 8 years of age. DESIGN: Population-based, record linkage, cohort study in England. SETTING: National Health Service (NHS) hospitals in England, UK. PARTICIPANTS: 1 018 136 live, singleton births in NHS hospitals in England between 1 January 2005 and 31 December 2006. MAIN OUTCOME MEASURES: Hospital admission costs from birth to age 8 years, estimated by gestational age at birth (<28, 28-29, 30-31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 and 42 weeks). RESULTS: Both birth admission and subsequent admission hospital costs decreased with increasing gestational age at birth. Differences in hospital admission costs between gestational age groups diminished with increasing age, particularly after the first 2 years following birth. Children born extremely preterm (<28 weeks) and very preterm (28-31 weeks) still had higher average hospital admission costs (£699 (95% CI £419 to £919) for <28 weeks; £434 (95% CI £305 to £563) for 28-31 weeks) during the eighth year of life compared with children born at 40 weeks (£109, 95% CI £104 to £114). Children born extremely preterm had the highest 8-year cumulative hospital admission costs per child (£80 559 (95% CI £79 238 to £82 019)), a large proportion of which was incurred during the first year after birth (£71 997 (95% CI £70 866 to £73 097)). CONCLUSIONS: The association between gestational age at birth and hospital admission costs persists into mid-childhood. The study results provide a useful costing resource for future economic evaluations focusing on preventive and treatment strategies for babies born preterm.

The Use of Multicriteria Decision Analysis to Support Decision Making in Healthcare: An Updated Systematic Literature Review.

OBJECTIVES: Multicriteria decision analysis (MCDA) is increasingly used for decision making in healthcare. However, its application in different decision-making contexts is still unclear. This study aimed to provide a comprehensive review of MCDA studies performed to inform decisions in healthcare and to summarize its application in different decision contexts. METHODS: We updated a systematic review conducted in 2013 by searching Embase, MEDLINE, and Google Scholar for MCDA studies in healthcare, published in English between August 2013 and November 2020. We also expanded the search by reviewing grey literature found via Trip Medical Database and Google, published between January 1990 and November 2020. A comprehensive template was developed to extract information about the decision context, criteria, methods, stakeholders involved, and sensitivity analyses conducted. RESULTS: From the 4295 identified studies, 473 studies were eligible for full-text review after assessing titles and abstracts. Of those, 228 studies met the inclusion criteria and underwent data extraction. The use of MCDA continues to grow in healthcare literature, with most of the studies (49%) informing priority-setting decisions. Safety, cost, and quality of care delivery are the most frequently used criteria, although there are considerable differences across decision contexts. Almost half of the MCDA studies used the linear additive model whereas scales and the analytical hierarchy process were the most used techniques for scoring and weighting, respectively. Not all studies report on each one of the MCDA steps, consider axiomatic properties, or justify the methods used. CONCLUSIONS: A guide on how to conduct and report MCDA that acknowledges the particularities of the different decision contexts and methods needs to be developed.

The impact of ultrasound-based antenatal screening strategies to detect vasa praevia in the United Kingdom: An exploratory study using decision analytic modelling methods.

The objective of this exploratory modelling study was to estimate the effects of second-trimester, ultrasound-based antenatal detection strategies for vasa praevia (VP) in a hypothetical cohort of pregnant women. For this, a decision-analytic tree model was developed covering four discrete detection pathways/strategies: no screening; screening targeted at women undergoing in-vitro fertilisation (IVF); screening targeted at women with low-lying placentas (LLP); screening targeted at women with velamentous cord insertion (VCI) or a bilobed or succenturiate (BL/S) placenta. Main outcome measures were the number of referrals to transvaginal sonography (TVS), diagnosed and undiagnosed cases of VP, overdetected cases of VCI, and VP-associated perinatal mortality. The greatest number of referrals to TVS occurred in the LLP-based (2,083) and VCI-based screening (1,319) pathways. These two pathways also led to the highest proportions of pregnancies diagnosed with VP (VCI-based screening: 552 [78.9% of all pregnancies]; LLP-based: 371 [53.5%]) and the lowest proportions of VP leading to perinatal death (VCI-based screening: 100 [14.2%]; LLP-based: 196 [28.0%]). In contrast, the IVF-based pathway resulted in 66 TVS referrals, 50 VP diagnoses (7.1% of all VP pregnancies), and 368 (52.6%) VP-associated perinatal deaths which was comparable to the no screening pathway (380 [54.3%]). The VCI-based pathway resulted in the greatest detection of VCI (14,238 [99.1%]), followed by the IVF-based pathway (443 [3.1%]); no VCI detection occurred in the LLP-based or no screening pathways. In conclusion, the model results suggest that a targeted LLP-based approach could detect a substantial proportion of VP cases, while avoiding VCI overdetection and requiring minimal changes to current clinical practice. High-quality data is required to explore the clinical and cost-effectiveness of this and other detection strategies further. This is necessary to provide a robust basis for future discussion about routine screening for VP.

Benefits and harms adopted by health economic assessments evaluating antenatal and newborn screening programmes in OECD countries: A systematic review of 336 articles and reports.

BACKGROUND: Health economic assessments are used to determine whether the resources needed to generate net benefit from a screening programme, driven by multiple complex benefits and harms, are justifiable. We systematically identified the benefits and harms incorporated within economic assessments evaluating antenatal and newborn screening programmes. METHODS: For this systematic review and thematic analysis, we searched the published and grey literature from January 2000 to January 2021. Studies that included an economic evaluation of an antenatal or newborn screening programme in an OECD country were eligible. We identified benefits and harms using an integrative descriptive analysis, and illustrated a thematic framework. (Systematic review registration PROSPERO, CRD42020165236). FINDINGS: The searches identified 52,244 articles and reports and 336 (242 antenatal and 95 newborn) were included. Eighty-six subthemes grouped into seven themes were identified: 1) diagnosis of screened for condition, 2) life years and health status adjustments, 3) treatment, 4) long-term costs, 5) overdiagnosis, 6) pregnancy loss, and 7) spillover effects on family members. Diagnosis of screened for condition (115 studies, 47.5%), life-years and health status adjustments (90 studies, 37.2%) and treatment (88 studies, 36.4%) accounted for most of the benefits and harms evaluating antenatal screening. The same themes accounted for most of the benefits and harms included in studies assessing newborn screening. Overdiagnosis and spillover effects tended to be ignored. INTERPRETATION: Our proposed framework can be used to guide the development of future health economic assessments evaluating antenatal and newborn screening programmes, to prevent exclusion of important potential benefits and harms.

The QALY at 50: One story many voices.

Research on quality adjusted life year (QALY) has been underway for just over 50 years, which seems like a suitable milestone to review its history. The purpose of this study is to provide a historical overview of why the QALY was developed, the key theoretical work undertaken by Torrance, Bush and Fanshel and how two seminal papers shaped its subsequent development. Moving the QALY forward - there are several historical and reflective exercises. The historical interplay between politics, policy and the challenges facing the National Health Service (NHS) in formulating the QALY concept in the UK has been explored in some depth already, whilst the conceptualization and development of the methodological framework is relatively underexplored. We address this gap by viewing the QALY through the lens of the methodological debates, reflecting upon two key papers underpinning the QALY methodology and how these methods have been developed over time. In part the changes in technology e.g. Google Scholar, and the availability of tools to search for early uses of the QALY allow us to better understand the historical context in which the theoretical development of the QALY has taken place. Here we celebrate two seminal papers that shaped early QALY development. The first section provides a history of these papers, summaries their contributions and explores the uptake of these papers over time. The second section reviews the methodological debates that have surrounded the QALY over the last 50 years and looks at how the QALY has moved to address these challenges. The third section presents the voices of diverse commentators representing the field of health economics who have contributed to the subsequent development of the QALY in both theoretical and empirical capacities and captures their thoughts about future research and policy use of QALYS.

Valuing child and adolescent health: a qualitative study on different perspectives and priorities taken by the adult general public.

BACKGROUND: Quantitative health preference research has shown that different "perspectives", defined here as who is imagined to be experiencing particular health states, impact stated preferences. This qualitative project aimed to elucidate this phenomenon, within the context of adults' valuation of child and adolescent health states. METHODS: Six focus groups with 30 members of the UK adult public were conducted between December 2019 and February 2020 and analysed using framework analysis. Each focus group had two stages. First, participants individually completed time trade-off tasks and a pairwise task (mirroring a discrete choice experiment without duration) for two EQ-5D-Y health states, assuming a series of perspectives: (a) themselves at current age; (b) another adult; (c) 10-year old child; (d) themselves as a 10-year old child. Second, a semi-structured discussion explored their responses. RESULTS: Participants' views were often heterogeneous, with some common themes. Qualitatively, participants expressed a different willingness to trade-off life years for a 10-year old child versus themselves or another adult, and this differed by the health profile and child imagined. The same health states were often viewed as having a different impact on utility for a 10-year old child than adults. Imagining a 10-year old child is difficult and there is variation in who is imagined. Participants found answering based on their own-adult perspective most acceptable. There were no strong preferences for prioritising child health over working-age adults' health. CONCLUSIONS: If an adult sample is used to value child- and adolescent-specific health states it is important to consider the perspective employed. Members of the adult public provide different responses when different perspectives are used due to differences in the perceived impact of the same health states. If adults are asked to imagine a child, we recommend that sampling is representative for parental status, since this can affect preferences.

Methods for evaluating the benefits and harms of antenatal and newborn screening programmes adopted by health economic assessments: protocol for a systematic review.

INTRODUCTION: Complex organisational arrangements are required to deliver antenatal and newborn screening programmes. Decision-makers consider the benefits and harms of screening when reviewing the evidence about these programmes. Economic evaluations contribute one important part of this assessment process. However, it is not fully understood what approaches health economic assessments have adopted to measure and value benefits and harms. This study aims to systematically review and critique the published and grey literature on methods for identifying, measuring and valuing the benefits and harms of antenatal and newborn screening adopted by health economic assessments. METHODS AND ANALYSIS: Nine bibliographic databases will be searched from 2000 onwards. These search strategies will be supplemented by manual reference searching of bibliographies, forward citation searching, contacts with experts, author searching and web searching for grey literature. Studies will be selected for review if they report health economic assessments of an antenatal or newborn screening programme. Assessments of title and abstracts and full reports will be undertaken independently with disagreements resolved through discussion. Data extraction will include fields to assess the reporting quality of the studies using the Consolidated Health Economic Evaluation Reporting Standards statement and a bespoke ancillary form to assess how benefits and harms have been accounted for. ETHICS AND DISSEMINATION: This is an evidence synthesis review from already published materials and hence ethics committee approval or written informed consent will not be required. Our results will be disseminated by publishing in high-impact peer-review journals and presenting at relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42020165236.

Economic evaluation of computerised interpretation of fetal heart rate during labour: a cost-consequence analysis alongside the INFANT study.

OBJECTIVE: Economic evaluation of computerised decision-support software intended to assist in the interpretation of a cardiotocography (CTG) during birth. DESIGN: Individual patient level data from the INFANT study (an unmasked randomised controlled trial). SETTING: Maternity units in the UK and Ireland. POPULATION: Singleton or twin pregnancy women of 35 weeks' gestation or more and receiving continuous electronic fetal monitoring during labour. INTERVENTION: Computerised decision-support software. METHODS: Cost-consequence analysis presenting costs and outcomes with a time horizon of 2 years from a government healthcare perspective. Unit cost data collected from a combination of primary and secondary sources. MAIN OUTCOME MEASURES: Primary clinical outcomes were (i) composite 'poor neonatal outcome' and (ii) developmental assessment at age 2 years in a subset of surviving children. Mean cost per mother and infant dyad from birth to hospital discharge, and from hospital discharge to 24 months follow-up. Maternal health-related quality of life was assessed at 12 and 24 months follow-up using the EuroQol three-level health-related quality of life instrument (EQ-5D-3L). RESULTS: Data were analysed for 46 042 women and 46 614 infants. No statistically significant differences were detected between trial arms in any of the primary clinical outcomes or maternal quality of life. No statistically significant differences in costs were detected in maternal or infant costs from trial entry to hospital discharge or overall from hospital discharge to 2-year follow-up. CONCLUSIONS: Decision-support software during labour is not associated with additional maternal or infant benefits and over a 2-year period the software did not lead to additional costs or savings to the National Health Service. TRIAL REGISTRATION NUMBER: ISRCTN98680152.

Benchmarking the Cost-Effectiveness of Interventions Delaying Diabetes: A Simulation Study Based on NAVIGATOR Data.

OBJECTIVE: To estimate using the UK Prospective Diabetes Study Outcomes Model Version 2 (UKPDS-OM2) the impact of delaying type 2 diabetes onset on costs and quality-adjusted life expectancy using trial participants who developed diabetes in the NAVIGATOR (Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research) study. RESEARCH DESIGN AND METHODS: We simulated the impact of delaying diabetes onset by 1-9 years, utilizing data from the 3,058 of 9,306 NAVIGATOR trial participants who developed type 2 diabetes. Costs and utility weights associated with diabetes and diabetes-related complications were obtained for the U.S. and U.K. settings, with costs expressed in 2017 values. We estimated discounted lifetime costs and quality-adjusted life years (QALYs) with 95% CIs. RESULTS: Gains in QALYs increased from 0.02 (U.S. setting, 95% CI 0.01, 0.03) to 0.15 (U.S. setting, 95% CI 0.10, 0.21) as the imposed time to diabetes onset was increased from 1 to 9 years, respectively. Savings in complication costs increased from $1,388 (95% CI $1,092, $1,669) for a 1-year delay to $8,437 (95% CI $6,611, $10,197) for a delay of 9 years. Interventions costing up to $567-$2,680 and £201-£947 per year would be cost-effective at $100,000 per QALY and £20,000 per QALY thresholds in the U.S. and U.K., respectively, as the modeled delay in diabetes onset was increased from 1 to 9 years. CONCLUSIONS: Simulating a hypothetical diabetes-delaying intervention provides guidance concerning the maximum cost and minimum delay in diabetes onset needed to be cost-effective. These results can inform the ongoing debate about diabetes prevention strategies and the design of future intervention studies.

International Valuation Protocol for the EQ-5D-Y-3L.

The EQ-5D-Y-3L is a generic, health-related, quality-of-life instrument for use in younger populations. Some methodological studies have explored the valuation of children's EQ-5D-Y-3L health states. There are currently no published value sets available for the EQ-5D-Y-3L that are appropriate for use in a cost-utility analysis. The aim of this article was to describe the development of the valuation protocol for the EQ-5D-Y-3L instrument. There were several research questions that needed to be answered to develop a valuation protocol for EQ-5D-Y-3L health states. Most important of these were: (1) Do we need to obtain separate values for the EQ-5D-Y-3L, or can we use the ones from the EQ-5D-3L? (2) Whose values should we elicit: children or adults? (3) Which valuation methods should be used to obtain values for child's health states that are anchored in Full health = 1 and Dead = 0? The EuroQol Research Foundation has pursued a research programme to provide insight into these questions. In this article, we summarized the results of the research programme concluding with the description of the features of the EQ-5D-Y-3L valuation protocol. The tasks included in the protocol for valuing EQ-5D-Y-3L health states are discrete choice experiments for obtaining the relative importance of dimensions/levels and composite time-trade-off for anchoring the discrete choice experiment values on 1 = Full Health and 0 = Dead. This protocol is now available for use by research teams to generate EQ-5D-Y-3L value sets for their countries allowing the implementation of a cost-utility analysis for younger populations.

Blood pressure monitoring in high-risk pregnancy to improve the detection and monitoring of hypertension (the BUMP 1 and 2 trials): protocol for two linked randomised controlled trials.

INTRODUCTION: Self-monitoring of blood pressure (BP) in pregnancy could improve the detection and management of pregnancy hypertension, while also empowering and engaging women in their own care. Two linked trials aim to evaluate whether BP self-monitoring in pregnancy improves the detection of raised BP during higher risk pregnancies (BUMP 1) and whether self-monitoring reduces systolic BP during hypertensive pregnancy (BUMP 2). METHODS AND ANALYSES: Both are multicentre, non-masked, parallel group, randomised controlled trials. Participants will be randomised to self-monitoring with telemonitoring or usual care. BUMP 1 will recruit a minimum of 2262 pregnant women at higher risk of pregnancy hypertension and BUMP 2 will recruit a minimum of 512 pregnant women with either gestational or chronic hypertension. The BUMP 1 primary outcome is the time to the first recording of raised BP by a healthcare professional. The BUMP 2 primary outcome is mean systolic BP between baseline and delivery recorded by healthcare professionals. Other outcomes will include maternal and perinatal outcomes, quality of life and adverse events. An economic evaluation of BP self-monitoring in addition to usual care compared with usual care alone will be assessed across both study populations within trial and with modelling to estimate long-term cost-effectiveness. A linked process evaluation will combine quantitative and qualitative data to examine how BP self-monitoring in pregnancy is implemented and accepted in both daily life and routine clinical practice. ETHICS AND DISSEMINATION: The trials have been approved by a Research Ethics Committee (17/WM/0241) and relevant research authorities. They will be published in peer-reviewed journals and presented at national and international conferences. If shown to be effective, BP self-monitoring would be applicable to a large population of pregnant women. TRIAL REGISTRATION NUMBER: NCT03334149.

Review of Valuation Methods of Preference-Based Measures of Health for Economic Evaluation in Child and Adolescent Populations: Where are We Now and Where are We Going?

Methods for measuring and valuing health benefits for economic evaluation and health technology assessment in adult populations are well developed. In contrast, methods for assessing interventions for child and adolescent populations lack detailed guidelines, particularly regarding the valuation of health and quality of life in these age groups. This paper critically examines the methodological considerations involved in the valuation of child- and adolescent-specific health-related quality of life by existing preference-based measures. It also describes the methodological choices made in the valuation of existing generic preference-based measures developed with and/or applied in child and adolescent populations: AHUM, AQoL-6D, CHU9D, EQ-5D-Y, HUI2, HUI3, QWB, 16D and 17D. The approaches used to value existing child- and adolescent-specific generic preference-based measures vary considerably. While the choice of whose preferences and which perspective to use is a matter of normative debate and ultimately for decision by reimbursement agencies and policy makers, greater research around these issues would be informative and would enrich these discussions. Research can also inform the other methodological choices required in the valuation of child and adolescent health states. Gaps in research evidence are identified around the impact of the child described in health state valuation exercises undertaken by adults, including the possibility of informed preferences; the appropriateness and acceptability of valuation tasks for adolescents, in particular tasks involving the state 'dead'; anchoring of adolescent preferences; and the generation and use of combined adult and adolescent preferences.

Feasibility, Validity and Differences in Adolescent and Adult EQ-5D-Y Health State Valuation in Australia and Spain: An Application of Best-Worst Scaling.

BACKGROUND: The measurement and valuation of health-related quality of life for and by young people are increasingly important, yet research on the impact of study perspective and validity of preferences obtained from young populations remains limited. OBJECTIVE: The objective of this study was to evaluate the feasibility and validity of collecting EQ-5D Youth version (EQ-5D-Y) preferences from adolescents, adults, and adults from a child perspective. METHODS: A profile case best-worst scaling (BWS) online survey was administered to representative Australian and Spanish adult (age ≥ 18 years) and child (age 11-17 years) samples. Adults were told to either answer from their own perspective or for a hypothetical 10-year-old child. Marginal best- and worst-choice frequencies, analysis of dominant choices, self-reported difficulty completing the tasks, and time to complete tasks were used to determine the validity of responses. RESULTS: In Australia, 2134 adults and 1010 adolescents completed the survey. In Spain, 2007 adults and 1000 adolescents completed it. Analysis of marginal choice frequencies and dominant choices indicated that the pattern of responses between adolescents and adults was similar. For Australian respondents, having no mobility problems was rated as best by adolescents, while adults rated having no pain and discomfort as 'best'. In Spain, both adults and adolescents rated no pain or discomfort as 'best'. Australian adolescents rated very worried, sad or unhappy as 'worst', while Spanish adolescents, Spanish adults and Australian adults rated a lot of pain and discomfort as 'worst'. CONCLUSIONS: Results suggest preferences from adolescents using direct BWS are valid. Our descriptive analysis also suggest that there are age-related and country-specific differences in elicitation values for the EQ-5D-Y.

Preferences for interventions designed to increase cervical screening uptake in non-attending young women: How findings from a discrete choice experiment compare with observed behaviours in a trial.

BACKGROUND: Young women's attendance at cervical screening in the UK is continuing to fall, and the incidence of invasive cervical cancer is rising. OBJECTIVES: We assessed the preferences of non-attending young women for alternative ways of delivering cervical screening. DESIGN: Postal discrete choice experiment (DCE) conducted during the STRATEGIC study of interventions for increasing cervical screening uptake. Attributes included action required to arrange a test, location of the test, availability of a nurse navigator and cost to the National Health Service. SETTING AND PARTICIPANTS: Non-attending young women in two UK regions. MAIN OUTCOME MEASURES: Responses were analysed using a mixed multinomial logit model. A predictive analysis identified the most preferable strategy compared to current screening. Preferences from the DCE were compared with observed behaviours during the STRATEGIC trial. RESULTS: The DCE response rate was 5.5% (222/4000), and 94% of respondents agreed screening is important. Preference heterogeneity existed around attributes with strong evidence for test location. Relative to current screening, unsolicited self-sampling kits for home use appeared most preferable. The STRATEGIC trial showed this same intervention to be most effective although many women who received it and were screened, attended for conventional cytology instead. CONCLUSIONS: The DCE and trial identified the unsolicited self-sampling kit as the most preferred/effective intervention. The DCE suggested that the decision of some women receiving the kit in the trial to attend for conventional cytology may be due to anxieties around home testing coupled with a knowledge that ignoring the kit could potentially have life-changing consequences.