Prevalence, diagnostic delay and economic burden of endometriosis and its impact on quality of life: results from an Eastern Mediterranean population.

BACKGROUND: There are limited data on endometriosis from the Eastern Mediterranean region. This study for the first time estimates the prevalence and impact of endometriosis on women in Northern Cyprus, an under-represented region in Europe. METHODS: Cyprus Women's Health Research Initiative, a cross-sectional study recruited 7646 women aged 18-55 in Northern Cyprus between January 2018 and February 2020. Cases were identified using self-reported and ultrasound data and two control groups were defined, with (n = 2922) and without (n = 4314) pain. Standardized tools, including the 11-point Numerical Rating Scale and the Short Form 36 Health Survey version 2, were used to assess pain and quality of life, respectively. RESULTS: Prevalence and median diagnostic delay of endometriosis were 5.4% [95% confidence interval (CI): 4.9-5.9%, n = 410] and 7 (interquartile range 15.5) years. Endometriosis cases experienced a higher prevalence of bladder pain compared with asymptomatic pain controls (6.3% vs. 1.0%, P < 0.001) and irritable bowel syndrome relating to pelvic pain compared with symptomatic (4.6% vs. 2.6%, P = 0.027) and asymptomatic (0.3%, P < 0.001) controls. The odds of endometriosis cases reporting an anxiety diagnosis was 1.56 (95% CI: 1.03-2.38) higher than the symptomatic and 1.95 (95% CI: 1.30-2.92) times higher than the asymptomatic controls. The physical component score of the health-related quality-of-life instrument suggested a significant difference between the endometriosis cases and the symptomatic controls (46.8 vs. 48.5, P = 0.034). Average annual economic cost of endometriosis cases was Int$9864 (95% CI: $8811-$10 917) including healthcare, costs relating to absence and loss of productivity at work. CONCLUSION: Prevalence was lower than the global 10% estimate, and substantial proportion of women without endometriosis reported moderate/severe pelvic pain hinting at many undiagnosed cases within this population. Coupled with lower quality of life, significant economic burden and underutilized pain management options, the study highlights multiple opportunities to improve care for endometriosis patients and women with pelvic pain.

The cost-effectiveness of oral contraceptives compared to 'no hormonal treatment' for endometriosis-related pain: An economic evaluation.

OBJECTIVE: To develop a preliminary cost-effectiveness model that compares oral contraceptives and 'no hormonal treatment' for the treatment of endometriosis-related pain. METHODS: A de novo preliminary state transition (Markov) model was developed. The model was informed by systematic literature review and expert opinion. The uncertainty around the results was assessed both by deterministic and probabilistic sensitivity analyses. The economic evaluation was conducted from National Health Service (NHS) England perspective. The main outcome measure was incremental cost per quality-adjusted life year (QALY), with cost-effectiveness plane and cost-effectiveness acceptability curves presented for alternative willingness-to-pay thresholds. RESULTS: Oral contraceptives dominated 'no hormonal treatment' and provided more QALYs at a lower cost than 'no hormonal treatment', with a cost-effectiveness probability of 98%. A one-way sensitivity analysis excluding general practitioner consultations showed that oral contraceptives were still cost-effective. CONCLUSIONS: The analyses showed that oral contraceptives could be an effective option for the treatment of endometriosis, as this treatment was shown to provide a higher level of QALYs at a lower cost, compared to 'no hormonal treatment'. The results are subject to considerable parameter uncertainty as a range of assumptions were required as part of the modelling process.

Estimating a Preference-Based Single Index Measuring the Quality-of-Life Impact of Self-Management for Diabetes.

OBJECTIVE: Self-management is becoming increasingly important in diabetes but is neglected in conventional preference-based measures. The objective of this paper was to generate health state utility values for a novel classification system measuring the quality-of-life impact of self-management for diabetes, which can be used to generate quality-adjusted life years (QALYs). METHODS: A large online survey was conducted using a discrete choice experiment (DCE), with duration as an additional attribute, on members of the UK general population ( n = 1,493) to elicit values for health (social limitations, mood, vitality, hypoglycaemia) and non-health (stress, hassle, control, support) aspects of self-management in diabetes. The data were modelled using a conditional fixed-effects logit model and utility estimates were anchored on the one to zero (full health to dead) scale. RESULTS: The model produced significant and consistent coefficients, with one logical inconsistency and 3 insignificant coefficients for the milder levels of some attributes. The anchored utilities ranged from 1 for the best state to -0.029 for the worst state (meaning worse than dead) defined by the classification system. CONCLUSION: The results presented here can potentially be used to generate utility values capturing the day to day impact of interventions in diabetes on both health and self-management. These utility values can potentially be used to generate QALYs for economic models of the cost-effectiveness of interventions in diabetes.

Cost-effectiveness of insulin pumps compared with multiple daily injections both provided with structured education for adults with type 1 diabetes: a health economic analysis of the Relative Effectiveness of Pumps over Structured Education (REPOSE) randomised controlled trial.

OBJECTIVES: To assess the long-term cost-effectiveness of insulin pumps and Dose Adjustment for Normal Eating (pumps+DAFNE) compared with multiple daily insulin injections and DAFNE (MDI+DAFNE) for adults with type 1 diabetes mellitus (T1DM) in the UK. METHODS: We undertook a cost-utility analysis using the Sheffield Type 1 Diabetes Policy Model and data from the Relative Effectiveness of Pumps over Structured Education (REPOSE) trial to estimate the lifetime incidence of diabetic complications, intervention-based resource use and associated effects on costs and quality-adjusted life years (QALYs). All economic analyses took a National Health Service and personal social services perspective and discounted costs and QALYs at 3.5% per annum. A probabilistic sensitivity analysis was performed on the base case. Further uncertainties in the cost of pumps and the evidence used to inform the model were explored using scenario analyses. SETTING: Eight diabetes centres in England and Scotland. PARTICIPANTS: Adults with T1DM who were eligible to receive a structured education course and did not have a strong clinical indication or a preference for a pump. INTERVENTION: Pumps+DAFNE. COMPARATOR: MDI+DAFNE. MAIN OUTCOME MEASURES: Incremental costs, incremental QALYs gained and incremental cost-effectiveness ratios (ICERs). RESULTS: Compared with MDI+DAFNE, pumps+DAFNE was associated with an incremental discounted lifetime cost of +£18 853 (95% CI £6175 to £31 645) and a gain in discounted lifetime QALYs of +0.13 (95% CI -0.70 to +0.96). The base case mean ICER was £142 195 per QALY gained. The probability of pump+DAFNE being cost-effective using a cost-effectiveness threshold of £20 000 per QALY gained was 14.0%. All scenario and subgroup analyses examined indicated that the ICER was unlikely to fall below £30 000 per QALY gained. CONCLUSIONS: Our analysis of the REPOSE data suggests that routine use of pumps in adults without an immediate clinical need for a pump, as identified by National Institute for Health and Care Excellence, would not be cost-effective. TRIAL REGISTRATION NUMBER: ISRCTN61215213.

Using a Discrete-Choice Experiment Involving Cost to Value a Classification System Measuring the Quality-of-Life Impact of Self-Management for Diabetes.

OBJECTIVES: To describe the use of a novel approach in health valuation of a discrete-choice experiment (DCE) including a cost attribute to value a recently developed classification system for measuring the quality-of-life impact (both health and treatment experience) of self-management for diabetes. METHODS: A large online survey was conducted using DCE with cost on UK respondents from the general population (n = 1497) and individuals with diabetes (n = 405). The data were modeled using a conditional logit model with robust standard errors. The marginal rate of substitution was used to generate willingness-to-pay (WTP) estimates for every state defined by the classification system. Robustness of results was assessed by including interaction effects for household income. RESULTS: There were some logical inconsistencies and insignificant coefficients for the milder levels of some attributes. There were some differences in the rank ordering of different attributes for the general population and diabetic patients. The WTP to avoid the most severe state was £1118.53 per month for the general population and £2356.02 per month for the diabetic patient population. The results were largely robust. CONCLUSIONS: Health and self-management can be valued in a single classification system using DCE with cost. The marginal rate of substitution for key attributes can be used to inform cost-benefit analysis of self-management interventions in diabetes using results from clinical studies in which this new classification system has been applied. The method shows promise, but found large WTP estimates exceeding the cost levels used in the survey.

The Capability Approach: A Critical Review of Its Application in Health Economics.

The capability approach is an approach to assessing well-being developed by Amartya Sen. Interest in this approach has resulted in several attempts to develop questionnaires to measure and value capability at an individual level in health economics. This commentary critically reviews the ability of these questionnaires to measure and value capability. It is argued that the method used in the questionnaires to measure capability will result in a capability set that is an inaccurate description of the individual's true capability set. The measured capability set will either represent only one combination and ignore the value of choice in the capability set, or represent one combination that is not actually achievable by the individual. In addition, existing methods of valuing capability may be inadequate because they do not consider that capability is a set. It may be practically more feasible to measure and value capability approximately rather than directly. Suggestions are made on how to measure and value an approximation to capability, but further research is required to implement the suggestions.

COST-EFFECTIVENESS OF STRUCTURED EDUCATION IN CHILDREN WITH TYPE-1 DIABETES MELLITUS.

OBJECTIVES: Kids in Control OF Food (KICk-OFF) is a 5-day structured education program for 11- to 16-year-olds with type 1 diabetes mellitus (T1DM) who are using multiple daily insulin injections. This study evaluates the cost-effectiveness of the KICk-OFF education program compared with the usual care using data from the KICk-OFF trial. METHODS: The short-term within-trial analysis covers the 2-year postintervention period. Data on glycated hemoglobin (HbA1c), severe hypoglycemia, and diabetic ketoacidosis (DKA) were collected over a 2-year follow-up period. Sub-group analyses have been defined on the basis of baseline HbA1c being below 7.5 percent (58.5 mmol/mol) (low group), between 7.5 percent and 9.5 percent (80.3 mmol/mol) (medium group), and over 9.5 percent (high group). The long-term cost-effectiveness evaluation has been conducted by using The Sheffield Type 1 Diabetes Policy Model, which is a patient-level simulation model on T1DM. It includes long-term microvascular (retinopathy, neuropathy, and nephropathy) and macrovascular (myocardial infarction, stroke, revascularization, and angina) diabetes-related complications and acute adverse events (severe hypoglycemia and DKA). RESULTS: The most favorable within-trial scenario for the KICk-OFF arm led to an incremental cost-effectiveness ratio (ICER) of £23,688 (base year 2009) with a cost-effectiveness probability of 41.3 percent. Simulating the long-term complications using the full cohort data, the mean ICER for the base case was £28,813 (base year 2011) and the probability of the KICk-OFF intervention being cost-effective at £20,000/QALY threshold was 42.6 percent, with considerable variation due to treatment effect duration. For the high HbA1c sub-group, the KICk-OFF arm was "dominant" (meaning it provided better health gains at lower costs than usual care) over the usual care arm in each scenario considered. CONCLUSIONS: For the whole study population, the cost-effectiveness of KICk-OFF depends on the assumption for treatment effect duration. For the high baseline HbA1c sub-group, KICk-OFF arm was estimated to be dominant over the usual care arm regardless of the assumption on the treatment effect duration.

Infliximab, adalimumab and golimumab for treating moderately to severely active ulcerative colitis after the failure of conventional therapy (including a review of TA140 and TA262): clinical effectiveness systematic review and economic model.

BACKGROUND: Ulcerative colitis (UC) is the most common form of inflammatory bowel disease in the UK. UC can have a considerable impact on patients' quality of life. The burden for the NHS is substantial. OBJECTIVES: To evaluate the clinical effectiveness and safety of interventions, to evaluate the incremental cost-effectiveness of all interventions and comparators (including medical and surgical options), to estimate the expected net budget impact of each intervention, and to identify key research priorities. DATA SOURCES: Peer-reviewed publications, European Public Assessment Reports and manufacturers' submissions. The following databases were searched from inception to December 2013 for clinical effectiveness searches and from inception to January 2014 for cost-effectiveness searches for published and unpublished research evidence: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, The Cochrane Library including the Cochrane Systematic Reviews Database, Cochrane Controlled Trials Register, Database of Abstracts of Reviews of Effects, the Health Technology Assessment database and NHS Economic Evaluation Database; ISI Web of Science, including Science Citation Index, and the Conference Proceedings Citation Index-Science and Bioscience Information Service Previews. The US Food and Drug Administration website and the European Medicines Agency website were also searched, as were research registers, conference proceedings and key journals. REVIEW METHODS: A systematic review [including network meta-analysis (NMA)] was conducted to evaluate the clinical effectiveness and safety of named interventions. The health economic analysis included a review of published economic evaluations and the development of a de novo model. RESULTS: Ten randomised controlled trials were included in the systematic review. The trials suggest that adult patients receiving infliximab (IFX) [Remicade(®), Merck Sharp & Dohme Ltd (MSD)], adalimumab (ADA) (Humira(®), AbbVie) or golimumab (GOL) (Simponi(®), MSD) were more likely to achieve clinical response and remission than those receiving placebo (PBO). Hospitalisation data were limited, but suggested more favourable outcomes for ADA- and IFX-treated patients. Data on the use of surgical intervention were sparse, with a potential benefit for intervention-treated patients. Data were available from one trial to support the use of IFX in paediatric patients. Safety issues identified included serious infections, malignancies and administration site reactions. Based on the NMA, in the induction phase, all biological treatments were associated with statistically significant beneficial effects relative to PBO, with the greatest effect associated with IFX. For patients in response following induction, all treatments except ADA and GOL 100 mg at 32-52 weeks were associated with beneficial effects when compared with PBO, although these were not significant. The greatest effects at 8-32 and 32-52 weeks were associated with 100 mg of GOL and 5 mg/kg of IFX, respectively. For patients in remission following induction, all treatments except ADA at 8-32 weeks and GOL 50 mg at 32-52 weeks were associated with beneficial effects when compared with PBO, although only the effect of ADA at 32-52 weeks was significant. The greatest effects were associated with GOL (at 8-32 weeks) and ADA (at 32-52 weeks). The economic analysis suggests that colectomy is expected to dominate drug therapies, but for some patients, colectomy may not be considered acceptable. In circumstances in which only drug options are considered, IFX and GOL are expected to be ruled out because of dominance, while the incremental cost-effectiveness ratio for ADA versus conventional treatment is approximately £50,300 per QALY gained. LIMITATIONS: The health economic model is subject to several limitations: uncertainty associated with extrapolating trial data over a lifetime horizon, the model does not consider explicit sequential pathways of non-biological treatments, and evidence relating to complications of colectomy was identified through consideration of approaches used within previous models rather than a full systematic review. CONCLUSIONS: Adult patients receiving IFX, ADA or GOL were more likely to achieve clinical response and remission than those receiving PBO. Further data are required to conclusively demonstrate the effect of interventions on hospitalisation and surgical outcomes. The economic analysis indicates that colectomy is expected to dominate medical treatments for moderate to severe UC. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013006883. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

A Model-Based Economic Evaluation of Biologic and Non-Biologic Options for the Treatment of Adults with Moderately-to-Severely Active Ulcerative Colitis after the Failure of Conventional Therapy.

BACKGROUND: Ulcerative colitis (UC) is the most common form of inflammatory bowel disease in the UK. Medical management aims to induce and maintain remission and to avoid complications and the necessity for surgical intervention. Colectomy removes the source of inflammation but is associated with morbidity and mortality. Newer anti-tumour necrosis factor (TNF)-α therapies may improve medical outcomes, albeit at an increased cost. OBJECTIVE: Our objective was to assess the incremental cost effectiveness of infliximab, adalimumab and golimumab versus conventional therapy and surgery from a National Health Service (NHS) and Personal Social Services (PSS) perspective over a lifetime horizon. METHODS: A Markov model was developed with health states defined according to whether the patient is alive or dead, current treatments received, history of colectomy and level of disease control. Transition probabilities were derived from network meta-analyses (NMAs) of trials of anti-TNF-α agents in the moderate-to-severe UC population. Health utilities, colectomy rates, surgical complications and resource use estimates were derived from literature. Unit costs were drawn from standard costing sources and literature and were valued at year 2013/2014 values. RESULTS: For patients in whom surgery is an option, colectomy is expected to dominate all medical treatment options. For patients in whom colectomy is not an option, infliximab and golimumab are expected to be ruled out due to dominance, whilst the incremental cost-effectiveness ratio (ICER) for adalimumab versus conventional treatment is expected to be approximately £50,278 per quality-adjusted life-year (QALY) gained. CONCLUSIONS: Based on the NMAs, the ICERs for anti-TNF-α therapy versus conventional treatment or surgery are expected to be at best, in excess of £50,000 per QALY gained. The cost effectiveness of withdrawing biologic therapy upon remission and re-treating relapse is unknown.

The Economic Impact of Lower Protein Infant Formula for the Children of Overweight and Obese Mothers.

The global prevalence of obesity is rising rapidly, highlighting the importance of understanding risk factors related to the condition. Childhood obesity, which has itself become increasingly prevalent, is an important predictor of adulthood obesity. Studies suggest that the protein content consumed in infanthood is an important predictor of weight gain in childhood, which may contribute to higher body mass index (BMI). For instance, there is evidence that a lower protein infant formula (lpIF) for infants of overweight or obese mothers can offer advantages over currently-used infant formulas with regard to preventing excessive weight gain. The current study used health economic modelling to predict the long-term clinical and economic outcomes in Mexico associated with lpIF compared to a currently-used formula. A discrete event simulation was constructed to extrapolate the outcomes of trials on the use of formula in infanthood to changes in lifetime BMI, the health outcomes due to the changes in BMI and the healthcare system costs, productivity and quality of life impact associated with these outcomes. The model predicts that individuals who receive lpIF in infancy go on to have lower BMI levels throughout their lives, are less likely to be obese or develop obesity-related disease, live longer, incur fewer health system costs and have improved productivity. Simulation-based economic modelling suggests that the benefits seen in the short term, with the use of lpIF over a currently-used formula, could translate into considerable health and economic benefits in the long term. Modelling over such long timeframes is inevitably subject to uncertainty. Further research should be undertaken to improve the certainty of the model.

Incorporating Psychological Predictors of Treatment Response into Health Economic Simulation Models: A Case Study in Type 1 Diabetes.

BACKGROUND: . Health economic modeling has paid limited attention to the effects that patients' psychological characteristics have on the effectiveness of treatments. This case study tests 1) the feasibility of incorporating psychological prediction models of treatment response within an economic model of type 1 diabetes, 2) the potential value of providing treatment to a subgroup of patients, and 3) the cost-effectiveness of providing treatment to a subgroup of responders defined using 5 different algorithms. METHODS: . Multiple linear regressions were used to investigate relationships between patients' psychological characteristics and treatment effectiveness. Two psychological prediction models were integrated with a patient-level simulation model of type 1 diabetes. Expected value of individualized care analysis was undertaken. Five different algorithms were used to provide treatment to a subgroup of predicted responders. A cost-effectiveness analysis compared using the algorithms to providing treatment to all patients. RESULTS: . The psychological prediction models had low predictive power for treatment effectiveness. Expected value of individualized care results suggested that targeting education at responders could be of value. The cost-effectiveness analysis suggested, for all 5 algorithms, that providing structured education to a subgroup of predicted responders would not be cost-effective. LIMITATIONS: . The psychological prediction models tested did not have sufficient predictive power to make targeting treatment cost-effective. The psychological prediction models are simple linear models of psychological behavior. Collection of data on additional covariates could potentially increase statistical power. CONCLUSIONS: . By collecting data on psychological variables before an intervention, we can construct predictive models of treatment response to interventions. These predictive models can be incorporated into health economic models to investigate more complex service delivery and reimbursement strategies.

Are policy decisions on surgical procedures informed by robust economic evidence? A systematic review.

OBJECTIVES: The aim of this study was to examine the empirical and methodological cost-effectiveness evidence of surgical interventions for breast, colorectal, or prostate cancer. METHODS: A systematic search of seven databases including MEDLINE, EMBASE, and NHSEED, research registers, the NICE Web site and conference proceedings was conducted in April 2012. Study quality was assessed in terms of meeting essential, preferred and UK NICE specific requirements for economic evaluations. RESULTS: The seventeen (breast = 3, colorectal = 7, prostate = 7) included studies covered a broad range of settings (nine European; eight non-European) and six were published over 10 years ago. The populations, interventions and comparators were generally well defined. Very few studies were informed by literature reviews and few used synthesized clinical evidence. Although the interventions had potential differential effects on recurrence and mortality rates, some studies used relatively short time horizons. Univariate sensitivity analyses were reported in all studies but less than a third characterized all uncertainty with a probabilistic sensitivity analysis. Although a third of studies incorporated patients' health-related quality of life data, only four studies used social tariff values. CONCLUSIONS: There is a dearth of recent robust evidence describing the cost-effectiveness of surgical interventions in the management of breast, colorectal and prostate cancers. Many of the recent publications did not satisfy essential methodological requirements such as using clinical evidence informed by a systematic review and synthesis. Given the ratio of potential benefit and harms associated with cancer surgery and the volume of resources consumed by these, there is an urgent need to increase economic evaluations of these technologies.

Principles of health economic evaluations of lipid-lowering strategies.

PURPOSE OF REVIEW: Policy decision-making in cardiovascular disease is increasingly informed by the results generated from decision-analytic models (DAMs). The methodological approaches and assumptions used in these DAMs impact on the results generated and can influence a policy decision based on a cost per quality-adjusted life year (QALY) threshold. Decision makers need to be provided with a clear understanding of the key sources of evidence and how they are used in the DAM to make an informed judgement on the quality and appropriateness of the results generated. RECENT FINDINGS: Our review identified 12 studies exploring the cost-effectiveness of pharmaceutical lipid-lowering interventions published since January 2010. All studies used Markov models with annual cycles to represent the long-term clinical pathway. Important differences in the model structures and evidence base used within the DAMs were identified. Whereas the reporting standards were reasonably good, there were many instances when reporting of methods could be improved, particularly relating to baseline risk levels, long-term benefit of treatment and health state utility values. SUMMARY: There is a scope for improvement in the reporting of evidence and modelling approaches used within DAMs to provide decision makers with a clearer understanding of the quality and validity of the results generated. This would be assisted by fuller publication of models, perhaps through detailed web appendices.