Cost-Effectiveness Analysis of Prostate Cancer Screening in the UK: A Decision Model Analysis Based on the CAP Trial.

BACKGROUND AND OBJECTIVE: Most guidelines in the UK, Europe and North America do not recommend organised population-wide screening for prostate cancer. Prostate-specific antigen-based screening can reduce prostate cancer-specific mortality, but there are concerns about overdiagnosis, overtreatment and economic value. The aim was therefore to assess the cost effectiveness of eight potential screening strategies in the UK. METHODS: We used a cost-utility analysis with an individual-based simulation model. The model was calibrated to data from the 10-year follow-up of the Cluster Randomised Trial of PSA Testing for Prostate Cancer (CAP). Treatment effects were modelled using data from the Prostate Testing for Cancer and Treatment (ProtecT) trial. The participants were a hypothetical population of 10 million men in the UK followed from age 30 years to death. The strategies were: no screening; five age-based screening strategies; adaptive screening, where men with an initial prostate-specific antigen level of < 1.5 ng/mL are screened every 6 years and those above this level are screened every 4 years; and two polygenic risk-stratified screening strategies. We assumed the use of pre-biopsy multi-parametric magnetic resonance imaging for men with prostate-specific antigen ≥ 3 ng/mL and combined transrectal ultrasound-guided and targeted biopsies. The main outcome measures were projected lifetime costs and quality-adjusted life-years from a National Health Service perspective. RESULTS: All screening strategies increased costs compared with no screening, with the majority also increasing quality-adjusted life-years. At willingness-to-pay thresholds of £20,000 or £30,000 per quality-adjusted life-year gained, a once-off screening at age 50 years was optimal, although this was sensitive to the utility estimates used. Although the polygenic risk-stratified screening strategies were not on the cost-effectiveness frontier, there was evidence to suggest that they were less cost ineffective than the alternative age-based strategies. CONCLUSIONS: Of the prostate-specific antigen-based strategies compared, only a once-off screening at age 50 years was potentially cost effective at current UK willingness-to-pay thresholds. An additional follow-up of CAP to 15 years may reduce uncertainty about the cost effectiveness of the screening strategies.

Systematic Review of Cost-Effectiveness Models in Prostate Cancer: Exploring New Developments in Testing and Diagnosis.

OBJECTIVES: Recent innovations in prostate cancer diagnosis include new biomarkers and more accurate biopsy methods. This study assesses the evidence base on cost-effectiveness of these developments (eg, Prostate Health Index and magnetic resonance imaging [MRI]-guided biopsy) and identifies areas of improvement for future cost-effectiveness models. METHODS: A systematic review using the National Health Service Economic Evaluation Database, MEDLINE, Embase, Health Technology Assessment databases, National Institute for Health and Care Excellence guidelines, and United Kingdom National Screening Committee guidance was performed, between 2009 and 2021. Relevant data were extracted on study type, model inputs, modeling methods and cost-effectiveness conclusions, and results narratively synthesized. RESULTS: A total of 22 model-based economic evaluations were included. A total of 11 compared the cost-effectiveness of new biomarkers to prostate-specific antigen testing alone and all found biomarkers to be cost saving. A total of 8 compared MRI-guided biopsy methods to transrectal ultrasound-guided methods and found MRI-guided methods to be most cost-effective. Newer detection methods showed a reduction in unnecessary biopsies and overtreatment. The most cost-effective follow-up strategy in men with a negative initial biopsy was uncertain. Many studies did not model for stage or grade of cancer, cancer progression, or the entire testing and treatment pathway. Few fully accounted for uncertainty. CONCLUSIONS: This review brings together the cost-effectiveness literature for novel diagnostic methods in prostate cancer, showing that most studies have found new methods to be more cost-effective than standard of care. Several limitations of the models were identified, however, limiting the reliability of the results. Areas for further development include accurately modeling the impact of early diagnostic tests on long-term outcomes of prostate cancer and fully accounting for uncertainty.

Challenges in Using Recommended Quality of Life Measures to Assess Fluctuating Health: A Think-Aloud Study to Understand How Recall and Timing of Assessment Influence Patient Responses.

BACKGROUND: It can be challenging to measure quality of life to calculate quality-adjusted life-years in recurrent fluctuating health states, as quality of life can constantly change. It is not clear how patients who experience fluctuations complete measures and how assessment timing and recall influence responses. OBJECTIVE: We aimed to understand how patients with fluctuating health complete widely recommended and commonly used measures (EQ-5D-5L, EORTC QLQ-C30 and SF-12) and the extent to which the recall period ('health today', 'past week' and 'past 4 weeks') and timing of assessment influence the way that patients complete these questionnaires. METHODS: Twenty-four adult patients undergoing chemotherapy for urological, gynaecological or bowel cancers in the UK participated in think-aloud interviews, while completing the measures, completed a pictorial task illustrating how quality of life changed during the chemotherapy cycle and took part in semi-structured interviews. Transcripts were analysed using constant comparison. RESULTS: Patients were consistent in describing their quality of life as changing considerably throughout a chemotherapy cycle. The shorter recall period of 'health today' does not adequately represent patients' quality of life because of fluctuations, patients remarked they could give a different answer depending on the timing of assessment, and many struggled to combine the "ups and downs" to answer measures with longer recall ('past week' and 'past 4 weeks'). Across all measures, patients attempted to provide averages, adopt the peak-end rule or focus on the best part of their experience. Patients commonly used more than one approach when completing a given questionnaire as well as across questionnaires. CONCLUSIONS: Patients who experience recurrent fluctuations in health are unable to provide meaningful responses about their quality of life when completing quality-of-life measures due to the recall period and timing of assessment. The use of such responses to calculate health state values in economic evaluations to inform resource allocation decisions in fluctuating conditions must be questioned.

Measuring capability wellbeing in adults at different stages of life for use in economic evaluation of health and care interventions: a qualitative investigation in people requiring kidney care.

PURPOSE: Capability wellbeing measures, such as the ICECAP measures, have been proposed for use in economic evaluations to capture broader outcomes of health and care interventions. The ICECAP measures have been developed to reflect capabilities at different stages of life. Some patient groups include patients of different ages and at different stages of life, so it is not always apparent which ICECAP measure is most relevant. This study explores the impact of age and life stage on completion, where both ICECAP-A and ICECAP-O were completed by the same patient. METHODS: A think-aloud study, and an associated semi-structured interview were conducted with people receiving kidney care as a renal outpatient, kidney transplant outpatient, or through receiving facility-based haemodialysis. Qualitative analysis focused on (1) differences in responses across measures by individuals, where attributes had conceptual overlap, (2) key factors in self-reported capability levels, and (3) measure preference. RESULTS: Thirty participants were included in the study, with a mix of older and younger adults. Attributes with similar wording across measures produced similar responses compared to attributes where wording differed. Age and health were key factors for self-reported capability levels. ICECAP-A was slightly preferred overall, including by older adults. CONCLUSION: This study suggests use of ICECAP-A in patients with certain chronic health conditions that include a mix of adults across the life course. This study highlights the importance of considering the stage of life when using capability measures and in economic evaluations of health and care interventions more generally.

Using a Modified Delphi Approach to Gain Consensus on Relevant Comparators in a Cost-Effectiveness Model: Application to Prostate Cancer Screening.

OBJECTIVE: Challenges can exist when framing the decision question in a cost-effectiveness analysis, particularly when there is disagreement among experts on relevant comparators. Using prostate cancer screening and recent developments in risk stratification, early-detection biomarkers, and diagnostic technologies as a case study, we report a modified Delphi approach to handle decision-question uncertainty. METHODS: The study involved two rounds of anonymous online questionnaires to identify the prostate cancer screening strategies that international researchers, clinicians and decision makers felt important to consider in a cost-effectiveness model. Both purposive and snowball sampling were used to recruit experts. The questionnaire was based on a review of the literature and was piloted for language, comprehension and ease of use prior to dissemination. In Round 1, respondents indicated their preferred screening strategy (including no screening) through a series of multiple-choice questions. The responses informed a set of 13 consensus statements, which respondents ranked their agreement with on a 9-point Likert scale (Round 2). Consensus was considered reached if > 70% of participants indicated agreement and < 15% indicated disagreement. RESULTS: Twenty participants completed Round 1 and 17 completed Round 2. Consensus was shown towards comparing no formal screening, age-based, and risk-based strategies. The risk-based approaches included screening only higher-risk men, using shorter screening intervals for higher-risk men, screening higher-risk men at an earlier age, and tailoring screening intervals based on prostate-specific antigen (PSA) level at a previous test. There was agreement that inclusion of MRI in the pathway should be considered, but disagreement on the inclusion of new biomarkers. CONCLUSION: In disease areas where technologies are rapidly evolving, a modified Delphi approach provides a useful tool to identify relevant comparators in an economic evaluation.

Response process validity of three patient reported outcome measures for people requiring kidney care: a think-aloud study using the EQ-5D-5L, ICECAP-A and ICECAP-O.

OBJECTIVES: To determine the response process validity, feasibility of completion, acceptability and preferences for three patient-reported outcome measures that could be used in economic evaluation-the EQ-5D-5L, ICECAP-A and ICECAP-O-in people requiring kidney care. DESIGN: Participants were asked to 'think-aloud' while completing the EQ-5D-5L, ICECAP-A and ICECAP-O, followed by a semistructured interview. Five raters identified errors or struggles in completing the measures from the think-aloud component of the transcripts. Patient preferences for measures were extracted from the semistructured interview. SETTING: Eligible patients were identified through a large UK secondary care renal centre. PARTICIPANTS: In total, 30 participants were included in the study, consisting of patients attending renal outpatients for chronic kidney disease (n=18), with a functioning kidney transplant (n=6) and receiving haemodialysis (n=6). RESULTS: Participants had few errors and struggles in completing the EQ-5D-5L (11% error rate, 3% struggle rate), ICECAP-A (2% error rate, 2% struggle rate) and ICECAP-O (4% error rate, 3% struggle rate). The main errors with the EQ-5D-5L were judgements that did not comply with the 'your health today' instruction. Comprehension errors were most prominent on ICECAP-O. Judgement errors were the only errors reported on ICECAP-A. Although the EQ-5D-5L had slightly more errors and struggles, it was the measure most preferred, with participants able to make a clearer link with EQ-5D-5L and their health condition. CONCLUSIONS: The EQ-5D-5L, ICECAP-A and ICECAP-O are feasible for people requiring kidney care to complete and can be included in studies conducting economic evaluations of kidney care interventions. Further research is required to assess how health (eg, EQ-5D) and capability (eg, ICECAP) measures can be included in an economic evaluation simultaneously, as well as what ICECAP measure(s) to include when patient groups straddle the age ranges for ICECAP-A (18 years and older) and ICECAP-O (65 years and older).

Measuring Quality-Adjusted Life-Years When Health Fluctuates.

Recurrent fluctuations in health states can occur as a result of long-term conditions with episodic symptoms or through side effects of cycles of treatment. Fluctuations and associated duration of symptoms can be predictable (eg, side effects of chemotherapy treatment) or unpredictable (eg, relapse in multiple sclerosis). Such recurrent fluctuations in health states can have an important impact on a person's health-related quality of life. When symptoms vary by time of day, day of the week, or during the month, it is challenging to obtain reliable health-related quality of life estimates for use in assessing cost-effectiveness of interventions. The adequacy of the quality of life estimate will be affected by (1) the standard recall period associated with the chosen measure (eg, "health today" EQ-5D, "past 4 weeks" for SF-36/SF-6D) and the way that respondents understand and make judgments about these recall periods, (2) the chosen time points for assessing health-related quality of life in relation to the fluctuations in health, and (3) the assumptions used to interpolate between measurement time points and thus calculate the quality-adjusted life-years. These issues have not received sufficient methodological attention and instead remain poorly accounted for in economic analyses. There is potential for these issues to considerably distort treatment decisions away from the optimal allocation. This article brings together evidence from health economics, psychology, and behavioral economics to explore these challenges in depth; presents the solutions that have been applied to date; and details a methodological research agenda for measuring quality-adjusted life-years in recurrent fluctuating health states.

The criterion validity of willingness to pay methods: A systematic review and meta-analysis of the evidence.

BACKGROUND: The contingent valuation (CV) method is used to estimate the willingness to pay (WTP) for services and products to inform cost benefit analyses (CBA). A long-standing criticism that stated WTP estimates may be poor indicators of actual WTP, calls into question their validity and the use of such estimates for welfare evaluation, especially in the health sector. Available evidence on the validity of CV studies so far is inconclusive. We systematically reviewed the literature to (1) synthesize the evidence on the criterion validity of WTP/willingness to accept (WTA), (2) undertake a meta-analysis, pooling evidence on the extent of variation between stated and actual WTP values and, (3) explore the reasons for the variation. METHODS: Eight electronic databases were searched, along with citations and reference reviews. 50 papers detailing 159 comparisons were identified and reviewed using a standard proforma. Two reviewers each were involved in the paper selection, review and data extraction. Meta-analysis was conducted using random effects models for ratios of means and percentage differences separately. Meta-bias was investigated using funnel plots. RESULTS: Hypothetical WTP was on average 3.2 times greater than actual WTP, with a range of 0.7-11.8 and 5.7 (0.0-13.6) for ratios of means and percentage differences respectively. However, key methodological differences between surveys of hypothetical and actual values were found. In the meta-analysis, high levels of heterogeneity existed. The overall effect size for mean summaries was 1.79 (1.56-2.04) and 2.37 (1.93-2.80) for percent summaries. Regression analyses identified mixed results on the influence of the different experimental protocols on the variation between stated and actual WTP values. Results indicating publication bias did not account for differences in study design. CONCLUSIONS: The evidence on the criterion validity for CV studies is more mixed than authors are representing because substantial differences in study design between hypothetical and actual WTP/WTA surveys are not accounted for.

The effectiveness and cost-effectiveness of a complex community sport intervention to increase physical activity: an interrupted time series design.

OBJECTIVES: An effectiveness and cost-effectiveness analyses of two-staged community sports interventions; taster sports sessions compared with portfolio of community sport sessions. DESIGN: Quasi-experiment using an interrupted time series design. SETTING: Community sports projects delivered by eight lead partners in London Borough of Hounslow, UK. PARTICIPANTS: Inactive people aged 14 plus years (n=246) were recruited between May 2013 and February 2014. INTERVENTIONS: Community sports interventions delivered in two stages, 6-week programme of taster sport sessions (stage 1) and 6-week programme of portfolio of community sporting sessions delivered by trained coaches (stage 2). OUTCOME MEASURES: (a) Change in days with ≥30 min of self-reported vigorous intensity physical activity (PA), moderate intensity PA, walking and sport; and (b) change in subjective well-being and EQ5D5L quality-adjusted life-years (QALYs). METHODS: Interrupted time series analysis evaluated the effectiveness of the two-staged sports programmes. Cost-effectiveness analysis compares stage 2 with stage 1 from a provider's perspective, reporting outcomes of incremental cost per QALY (2015/2016 price year). Uncertainty was assessed using deterministic and probabilistic sensitivity analyses. RESULTS: Compared with stage 1, counterfactual change at 21 days in PA was lower for vigorous (log odds: -0.52; 95% CI -1 to -0.03), moderate PA (-0.50; 95% CI 0.94 to 0.05) and sport(-0.56; 95% CI -1.02 to -0.10). Stage 2 increased walking (0.28; 95% CI 0.3 to 0.52). Effect overtime was similar. Counterfactual change at 21 days in well-being was positive particularly for 'happiness' (0.29; 95% CI 0.06 to 0.51). Stage 2 was more expensive (£101 per participant) but increased QALYs (0.001; 95% CI -0.034 to 0.036). Cost per QALY for stage 2 was £50 000 and has 29% chance of being cost-effective (£30 000 threshold). CONCLUSION: Community-based sport interventions could increase PA among inactive people. Less intensive sports sessions may be more effective and cost-effective.

Short-term and long-term cost-effectiveness of a pedometer-based exercise intervention in primary care: a within-trial analysis and beyond-trial modelling.

OBJECTIVES: A short-term and long-term cost-effectiveness analysis (CEA) of two pedometer-based walking interventions compared with usual care. DESIGN: (A) Short-term CEA: parallel three-arm cluster randomised trial randomised by household. (B) Long-term CEA: Markov decision model. SETTING: Seven primary care practices in South London, UK. PARTICIPANTS: (A) Short-term CEA: 1023 people (922 households) aged 45-75 years without physical activity (PA) contraindications. (b) Long-term CEA: a cohort of 100 000 people aged 59-88 years. INTERVENTIONS: Pedometers, 12-week walking programmes and PA diaries delivered by post or through three PA consultations with practice nurses. PRIMARY AND SECONDARY OUTCOME MEASURES: Accelerometer-measured change (baseline to 12 months) in average daily step count and time in 10 min bouts of moderate to vigorous PA (MVPA), and EQ-5D-5L quality-adjusted life-years (QALY). METHODS: Resource use costs (£2013/2014) from a National Health Service perspective, presented as incremental cost-effectiveness ratios for each outcome over a 1-year and lifetime horizon, with cost-effectiveness acceptability curves and willingness to pay per QALY. Deterministic and probabilistic sensitivity analyses evaluate uncertainty. RESULTS: (A) Short-term CEA: At 12 months, incremental cost was £3.61 (£109)/min in ≥10 min MVPA bouts for nurse support compared with control (postal group). At £20 000/QALY, the postal group had a 50% chance of being cost saving compared with control. (B) Long-term CEA: The postal group had more QALYs (+759 QALYs, 95% CI 400 to 1247) and lower costs (-£11 million, 95% CI -12 to -10) than control and nurse groups, resulting in an incremental net monetary benefit of £26 million per 100 000 population. Results were sensitive to reporting serious adverse events, excluding health service use, and including all participant costs. CONCLUSIONS: Postal delivery of a pedometer intervention in primary care is cost-effective long term and has a 50% chance of being cost-effective, through resource savings, within 1 year. Further research should ascertain maintenance of the higher levels of PA, and its impact on quality of life and health service use. TRIAL REGISTRATION NUMBER: ISRCTN98538934; Pre-results.

A pedometer-based walking intervention in 45- to 75-year-olds, with and without practice nurse support: the PACE-UP three-arm cluster RCT.

BACKGROUND: Guidelines recommend walking to increase moderate to vigorous physical activity (MVPA) for health benefits. OBJECTIVES: To assess the effectiveness, cost-effectiveness and acceptability of a pedometer-based walking intervention in inactive adults, delivered postally or through dedicated practice nurse physical activity (PA) consultations. DESIGN: Parallel three-arm trial, cluster randomised by household. SETTING: Seven London-based general practices. PARTICIPANTS: A total of 11,015 people without PA contraindications, aged 45-75 years, randomly selected from practices, were invited. A total of 6399 people were non-responders, and 548 people self-reporting achieving PA guidelines were excluded. A total of 1023 people from 922 households were randomised to usual care (n = 338), postal intervention (n = 339) or nurse support (n = 346). The recruitment rate was 10% (1023/10,467). A total of 956 participants (93%) provided outcome data. INTERVENTIONS: Intervention groups received pedometers, 12-week walking programmes advising participants to gradually add '3000 steps in 30 minutes' most days weekly and PA diaries. The nurse group was offered three dedicated PA consultations. MAIN OUTCOME MEASURES: The primary and main secondary outcomes were changes from baseline to 12 months in average daily step counts and time in MVPA (in ≥ 10-minute bouts), respectively, from 7-day accelerometry. Individual resource-use data informed the within-trial economic evaluation and the Markov model for simulating long-term cost-effectiveness. Qualitative evaluations assessed nurse and participant views. A 3-year follow-up was conducted. RESULTS: Baseline average daily step count was 7479 [standard deviation (SD) 2671], average minutes per week in MVPA bouts was 94 minutes (SD 102 minutes) for those randomised. PA increased significantly at 12 months in both intervention groups compared with the control group, with no difference between interventions; additional steps per day were 642 steps [95% confidence interval (CI) 329 to 955 steps] for the postal group and 677 steps (95% CI 365 to 989 steps) for nurse support, and additional MVPA in bouts (minutes per week) was 33 minutes per week (95% CI 17 to 49 minutes per week) for the postal group and 35 minutes per week (95% CI 19 to 51 minutes per week) for nurse support. Intervention groups showed no increase in adverse events. Incremental cost per step was 19p and £3.61 per minute in a ≥ 10-minute MVPA bout for nurse support, whereas the postal group took more steps and cost less than the control group. The postal group had a 50% chance of being cost-effective at a £20,000 per quality-adjusted life-year (QALY) threshold within 1 year and had both lower costs [-£11M (95% CI -£12M to -£10M) per 100,000 population] and more QALYs [759 QALYs gained (95% CI 400 to 1247 QALYs)] than the nurse support and control groups in the long term. Participants and nurses found the interventions acceptable and enjoyable. Three-year follow-up data showed persistent intervention effects (nurse support plus postal vs. control) on steps per day [648 steps (95% CI 272 to 1024 steps)] and MVPA bouts [26 minutes per week (95% CI 8 to 44 minutes per week)]. LIMITATIONS: The 10% recruitment level, with lower levels in Asian and socioeconomically deprived participants, limits the generalisability of the findings. Assessors were unmasked to the group. CONCLUSIONS: A primary care pedometer-based walking intervention in 45- to 75-year-olds increased 12-month step counts by around one-tenth, and time in MVPA bouts by around one-third, with similar effects for the nurse support and postal groups, and persistent 3-year effects. The postal intervention provides cost-effective, long-term quality-of-life benefits. A primary care pedometer intervention delivered by post could help address the public health physical inactivity challenge. FUTURE WORK: Exploring different recruitment strategies to increase uptake. Integrating the Pedometer And Consultation Evaluation-UP (PACE-UP) trial with evolving PA monitoring technologies. TRIAL REGISTRATION: Current Controlled Trials ISRCTN98538934. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 37. See the NIHR Journals Library website for further project information.

Cost-effectiveness of prostate cancer screening: a systematic review of decision-analytical models.

BACKGROUND: There is ongoing debate about the harms and benefits of a national prostate cancer screening programme. Several model-based cost-effectiveness analyses have been developed to determine whether the benefits of prostate cancer screening outweigh the costs and harms caused by over-detection and over-treatment, and the different approaches may impact results. METHODS: To identify models of prostate cancer used to assess the cost-effectiveness of prostate cancer screening strategies, a systematic review of articles published since 2006 was conducted using the NHS Economic Evaluation Database, Medline, EMBASE and HTA databases. The NICE website, UK National Screening website, reference lists from relevant studies were also searched and experts contacted. Key model features, inputs, and cost-effectiveness recommendations were extracted. RESULTS: Ten studies were included. Four of the studies identified some screening strategies to be potentially cost-effective at a PSA threshold of 3.0 ng/ml, including single screen at 55 years, annual or two yearly screens starting at 55 years old, and delayed radical treatment. Prostate cancer screening was modelled using both individual and cohort level models. Model pathways to reflect cancer progression varied widely, Gleason grade was not always considered and clinical verification was rarely outlined. Where quality of life was considered, the methods used did not follow recommended practice and key issues of overdiagnosis and overtreatment were not addressed by all studies. CONCLUSION: The cost-effectiveness of prostate cancer screening is unclear. There was no consensus on the optimal model type or approach to model prostate cancer progression. Due to limited data availability, individual patient-level modelling is unlikely to increase the accuracy of cost-effectiveness results compared with cohort-level modelling, but is more suitable when assessing adaptive screening strategies. Modelling prostate cancer is challenging and the justification for the data used and the approach to modelling natural disease progression was lacking. Country-specific data are required and recommended methods used to incorporate quality of life. Influence of data inputs on cost-effectiveness results need to be comprehensively assessed and the model structure and assumptions verified by clinical experts.

Sensitivity to scale of willingness-to-pay within the context of menorrhagia.

OBJECTIVES: Willingness-to-pay (WTP) provides a broad assessment of well-being, capturing benefits beyond health. However, the validity of the approach has been questioned and the evidence relating to the sensitivity of WTP to changes in health status is mixed. Using menorrhagia (heavy menstrual bleeding) as a case study, this exploratory study assesses the sensitivity to scale of WTP to change in health status as measured by a condition-specific measure, MMAS, which includes both health and non-health benefits. The relationship between EQ-5D and change in health status is also assessed. METHODS: Baseline EQ-5D and MMAS values were collected from women taking part in a randomized controlled trial for pharmaceutical treatment of menorrhagia. Following treatment, these measures were administered along with a WTP exercise. The relationship between the measures was assessed using Spearman's correlation analysis, and the sensitivity to scale of WTP was measured by identifying differences in WTP alongside differences in MMAS and EQ5D values. RESULTS: Our exploratory findings indicated that WTP, and not EQ-5D, was significantly positively correlated with change in MMAS, providing some evidence for convergent validity. These findings suggest that WTP is capturing the non-health benefits within the MMAS measure. Mean WTP also increased with percentage improvements in MMAS, suggesting sensitivity to scale. CONCLUSION: When compared to quality of life measured using the condition-specific MMAS measure, the convergent validity and sensitivity to scale of WTP is indicated. The findings suggest that WTP is more sensitive to change in MMAS, than with EQ-5D.

Cluster randomised controlled trial of a financial incentive for mothers to improve breast feeding in areas with low breastfeeding rates: the NOSH study protocol.

INTRODUCTION: Breast feeding can promote positive long-term and short-term health outcomes in infant and mother. The UK has one of the lowest breastfeeding rates (duration and exclusivity) in the world, resulting in preventable morbidities and associated healthcare costs. Breastfeeding rates are also socially patterned, thereby potentially contributing to health inequalities. Financial incentives have been shown to have a positive effect on health behaviours in previously published studies. METHODS AND ANALYSIS: Based on data from earlier development and feasibility stages, a cluster (electoral ward) randomised trial with mixed-method process and content evaluation was designed. The 'Nourishing Start for Health' (NOSH) intervention comprises a financial incentive programme of up to 6 months duration, delivered by front-line healthcare professionals, in addition to existing breastfeeding support. The intervention aims to increase the prevalence and duration of breast feeding in wards with low breastfeeding rates. The comparator is usual care (no offer of NOSH intervention). Routine data on breastfeeding rates at 6-8 weeks will be collected for 92 clusters (electoral wards) on an estimated 10,833 births. This sample is calculated to provide 80% power in determining a 4% point difference in breastfeeding rates between groups. Content and process evaluation will include interviews with mothers, healthcare providers, funders and commissioners of infant feeding services. The economic analyses, using a healthcare provider's perspective, will be twofold, including a within-trial cost-effectiveness analysis and beyond-trial modelling of longer term expectations for cost-effectiveness. Results of economic analyses will be expressed as cost per percentage point change in cluster level in breastfeeding rates between trial arms. In addition, we will present difference in resource use impacts for a range of acute conditions in babies aged 0-6 months. ETHICS AND DISSEMINATION: Participating organisations Research and Governance departments approved the study. Results will be published in peer-reviewed journals and at conference presentations. TRIAL REGISTRATION NUMBER: ISRCTN44898617; Pre-results.

Pharmaceutical treatments to prevent recurrence of endometriosis following surgery: a model-based economic evaluation.

OBJECTIVE: Conduct an economic evaluation based on best currently available evidence comparing alternative treatments levonorgestrel-releasing intrauterine system, depot-medroxyprogesterone acetate, combined oral contraceptive pill (COCP) and 'no treatment' to prevent recurrence of endometriosis after conservative surgery in primary care, and to inform the design of a planned trial-based economic evaluation. METHODS: We developed a state transition (Markov) model with a 36-month follow-up. The model structure was informed by a pragmatic review and clinical experts. The economic evaluation adopted a UK National Health Service perspective and was based on an outcome of incremental cost per quality-adjusted life year (QALY). As available data were limited, intentionally wide distributions were assigned around model inputs, and the average costs and outcome of the probabilistic sensitivity analyses were reported. RESULTS: On average, all strategies were more expensive and generated fewer QALYs compared to no treatment. However, uncertainty attributing to the transition probabilities affected the results. Inputs relating to effectiveness, changes in treatment and the time at which the change is made were the main causes of uncertainty, illustrating areas where robust and specific data collection is required. CONCLUSIONS: There is currently no evidence to support any treatment being recommended to prevent the recurrence of endometriosis following conservative surgery. The study highlights the importance of developing decision models at the outset of a trial to identify data requirements to conduct a robust post-trial analysis.

A randomised controlled trial of the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system in primary care against standard treatment for menorrhagia: the ECLIPSE trial.

BACKGROUND: Heavy menstrual bleeding (HMB) is a common problem, yet evidence to inform decisions about initial medical treatment is limited. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) (Mirena®, Bayer) compared with usual medical treatment, with exploration of women's perspectives on treatment. DESIGN: A pragmatic, multicentre randomised trial with an economic evaluation and a longitudinal qualitative study. SETTING: Women who presented in primary care. PARTICIPANTS: A total of 571 women with HMB. A purposeful sample of 27 women who were randomised or ineligible owing to treatment preference participated in semistructured face-to-face interviews around 2 and 12 months after commencing treatment. INTERVENTIONS: LNG-IUS or usual medical treatment (tranexamic acid, mefenamic acid, combined oestrogen-progestogen or progesterone alone). Women could subsequently swap or cease their allocated treatment. OUTCOME MEASURES: The primary outcome was the patient-reported score on the Menorrhagia Multi-Attribute Scale (MMAS) assessed over a 2-year period and then again at 5 years. Secondary outcomes included general quality of life (QoL), sexual activity, surgical intervention and safety. Data were analysed using iterative constant comparison. A state transition model-based cost-utility analysis was undertaken alongside the randomised trial. Quality-adjusted life-years (QALYs) were derived from the European Quality of Life-5 Dimensions (EQ-5D) and the Short Form questionnaire-6 Dimensions (SF-6D). The intention-to-treat analyses were reported as cost per QALY gained. Uncertainty was explored by conducting both deterministic and probabilistic sensitivity analyses. RESULTS: The MMAS total scores improved significantly in both groups at all time points, but were significantly greater for the LNG-IUS than for usual treatment [mean difference over 2 years was 13.4 points, 95% confidence interval (CI) 9.9 to 16.9 points; p < 0.001]. However, this difference between groups was reduced and no longer significant by 5 years (mean difference in scores 3.9 points, 95% CI -0.6 to 8.3 points; p = 0.09). By 5 years, only 47% of women had a LNG-IUS in place and 15% were still taking usual medical treatment. Five-year surgery rates were low, at 20%, and were similar, irrespective of initial treatments. There were no significant differences in serious adverse events between groups. Using the EQ-5D, at 2 years, the relative cost-effectiveness of the LNG-IUS compared with usual medical treatment was £1600 per QALY, which by 5 years was reduced to £114 per QALY. Using the SF-6D, usual medical treatment dominates the LNG-IUS. The qualitative findings show that women's experiences and expectations of medical treatments for HMB vary considerably and change over time. Women had high expectations of a prompt effect from medical treatments. CONCLUSIONS: The LNG-IUS, compared with usual medical therapies, resulted in greater improvement over 2 years in women's assessments of the effect of HMB on their daily routine, including work, social and family life, and psychological and physical well-being. At 5 years, the differences were no longer significant. A similar low proportion of women required surgical intervention in both groups. The LNG-IUS is cost-effective in both the short and medium term, using the method generally recommended by the National Institute for Health and Care Excellence. Using the alternative measures to value QoL will have a considerable impact on cost-effectiveness decisions. It will be important to explore the clinical and health-care trajectories of the ECLIPSE (clinical effectiveness and cost-effectiveness of levonorgestrel-releasing intrauterine system in primary care against standard treatment for menorrhagia) trial participants to 10 years, by which time half of the cohort will have reached menopause. TRIAL REGISTRATION: Current Controlled Trials ISRCTN86566246. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 88. See the NIHR Journals Library website for further project information.

Exploring the Use of Cost-Benefit Analysis to Compare Pharmaceutical Treatments for Menorrhagia.

BACKGROUND: The extra-welfarist theoretical framework tends to focus on health-related quality of life, whilst the welfarist framework captures a wider notion of well-being. EQ-5D and SF-6D are commonly used to value outcomes in chronic conditions with episodic symptoms, such as heavy menstrual bleeding (clinically termed menorrhagia). Because of their narrow-health focus and the condition's periodic nature these measures may be unsuitable. A viable alternative measure is willingness to pay (WTP) from the welfarist framework. OBJECTIVE: We explore the use of WTP in a preliminary cost-benefit analysis comparing pharmaceutical treatments for menorrhagia. METHODS: A cost-benefit analysis was carried out based on an outcome of WTP. The analysis is based in the UK primary care setting over a 24-month time period, with a partial societal perspective. Ninety-nine women completed a WTP exercise from the ex-ante (pre-treatment/condition) perspective. Maximum average WTP values were elicited for two pharmaceutical treatments, levonorgestrel-releasing intrauterine system (LNG-IUS) and oral treatment. Cost data were offset against WTP and the net present value derived for treatment. Qualitative information explaining the WTP values was also collected. RESULTS: Oral treatment was indicated to be the most cost-beneficial intervention costing £107 less than LNG-IUS and generating £7 more benefits. The mean incremental net present value for oral treatment compared with LNG-IUS was £113. The use of the WTP approach was acceptable as very few protests and non-responses were observed. CONCLUSION: The preliminary cost-benefit analysis results recommend oral treatment as the first-line treatment for menorrhagia. The WTP approach is a feasible alternative to the conventional EQ-5D/SF-6D approaches and offers advantages by capturing benefits beyond health, which is particularly relevant in menorrhagia.

Levonorgestrel-releasing intrauterine system vs. usual medical treatment for menorrhagia: an economic evaluation alongside a randomised controlled trial.

OBJECTIVE: To undertake an economic evaluation alongside the largest randomised controlled trial comparing Levonorgestrel-releasing intrauterine device ('LNG-IUS') and usual medical treatment for women with menorrhagia in primary care; and compare the cost-effectiveness findings using two alternative measures of quality of life. METHODS: 571 women with menorrhagia from 63 UK centres were randomised between February 2005 and July 2009. Women were randomised to having a LNG-IUS fitted, or usual medical treatment, after discussing with their general practitioner their contraceptive needs or desire to avoid hormonal treatment. The treatment was specified prior to randomisation. For the economic evaluation we developed a state transition (Markov) model with a 24 month follow-up. The model structure was informed by the trial women's pathway and clinical experts. The economic evaluation adopted a UK National Health Service perspective and was based on an outcome of incremental cost per Quality Adjusted Life Year (QALY) estimated using both EQ-5D and SF-6D. RESULTS: Using EQ-5D, LNG-IUS was the most cost-effective treatment for menorrhagia. LNG-IUS costs £100 more than usual medical treatment but generated 0.07 more QALYs. The incremental cost-effectiveness ratio for LNG-IUS compared to usual medical treatment was £1600 per additional QALY. Using SF-6D, usual medical treatment was the most cost-effective treatment. Usual medical treatment was both less costly (£100) and generated 0.002 more QALYs. CONCLUSION: Impact on quality of life is the primary indicator of treatment success in menorrhagia. However, the most cost-effective treatment differs depending on the quality of life measure used to estimate the QALY. Under UK guidelines LNG-IUS would be the recommended treatment for menorrhagia. This study demonstrates that the appropriate valuation of outcomes in menorrhagia is crucial.