Cost-effectiveness Benchmarks Research Articles

Exploring Structural Uncertainty in Cost-Effectiveness Modeling of Gestational Diabetes Screening: An Application Example from Norway.

Screening pregnant women for gestational diabetes mellitus (GDM) has recently been expanded in Norway, although screening eligibility criteria continue to be debated. We aimed to compare the cost-effectiveness of alternative GDM screening strategies and explored structural uncertainty and the value of future research in determining the most cost-effective eligibility criteria for GDM screening in Norway. We developed a probabilistic decision tree to estimate the total costs and health benefits (i.e., quality-adjusted life-years; QALYs) associated with 4 GDM screening strategies (universal, current guidelines, high-risk, and no screening). We identified the most cost-effective strategy as the strategy with the highest incremental cost-effectiveness ratio below a Norwegian benchmark for cost-effectiveness ($28,400/QALY). We excluded inconclusive evidence on the effects of screening on later maternal type 2 diabetes mellitus (T2DM) in the primary analysis but included this outcome in a secondary analysis using 2 different sources of evidence (i.e., Cochrane or US Preventive Services Task Force). To quantify decision uncertainty, we conducted scenario analysis and value-of-information analyses. Current screening recommendations were considered inefficient in all analyses, while universal screening was most cost-effective in our primary analysis ($26,014/QALY gained) and remained most cost-effective when we assumed a preventive effect of GDM treatment on T2DM. When we assumed no preventive effect, high-risk screening was preferred ($19,115/QALY gained). When we assumed GDM screening does not prevent perinatal death in scenario analysis, all strategies except no screening exceeded the cost-effectiveness benchmark. In most analyses, decision uncertainty was high. The most cost-effective screening strategy, ranging from no screening to universal screening, depended on the source and inclusion of GDM treatment effects on perinatal death and T2DM. Further research on these long-term outcomes could reduce decision uncertainty. This article analyses the cost-effectiveness of 4 alternative gestational diabetes mellitus (GDM) screening strategies in Norway: universal screening, current (broad) screening, high-risk screening, and no screening.The current Norwegian screening recommendations were considered inefficient under all analyses.The most cost-effective screening strategy ranged from no screening to universal screening depending on the source and inclusion of GDM treatment effects on later maternal diabetes and perinatal death.The parameters related to later maternal diabetes and perinatal death accounted for most of the decision uncertainty.

Cost-effectiveness of Empagliflozin in Patients With Heart Failure With Preserved Ejection Fraction

In the Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction (EMPEROR-Preserved), empagliflozin significantly reduced hospitalizations for heart failure while improving patient-reported health status compared with placebo. The long-term cost-effectiveness of empagliflozin among patients who have heart failure with preserved ejection fraction (HFpEF) remains unclear. To estimate the cost-effectiveness of empagliflozin in patients with HFpEF. This cost-effectiveness analysis performed from October 2021 to April 2022 included a Markov model using estimates of treatment efficacy, event probabilities, and utilities from EMPEROR-Preserved and published literature. Costs were derived from national surveys and pricing data sets. Quality of life was imputed from a heart failure-specific quality-of-life measure. Two analyses were performed, with and without a treatment effect on cardiovascular mortality. Subgroup analyses were based on diabetes status, ejection fraction, and health status impairment due to heart failure. The model reproduced the event rates and risk reduction with empagliflozin observed in EMPEROR-Preserved over 26 months of follow-up; future projections extended across the lifetime of patients. Empagliflozin or standard of care. Hospitalizations for heart failure, life-years, quality-adjusted life-years (QALYs), lifetime costs, and lifetime incremental cost-effectiveness ratio. A total of 5988 patients were included in the analysis, with a mean age of 72 years, New York Heart Association class II to IV heart failure, and left ventricular ejection fraction greater than 40%. At the Federal Supply Schedule price of $327 per month, empagliflozin yielded 0.06 additional QALYs and $26 257 incremental costs compared with standard of care, producing a cost per QALY gained of $437 442. Incremental costs consisted of total drug costs of $29 586 and savings of $3329 from reduced hospitalizations for heart failure. Cost-effectiveness was similar across subgroups. The results were most sensitive to the monthly cost, quality-of-life benefit, and mortality effect of empagliflozin. A price reduction to $153 per month, incremental utility of 0.02, or 8% reduction in cardiovascular mortality would bring empagliflozin to $180 000 per QALY gained, the threshold for intermediate value. Using Medicare Part D monthly pricing of $375 after rebates and $511 before rebates, empagliflozin would remain low value at $509 636 and $710 825 per QALY gained, respectively. Cost-effectiveness estimates were robust to variation in the frequency and disutility of heart failure hospitalizations. In this economic evaluation, based on current cost-effectiveness benchmarks, empagliflozin provides low economic value compared with standard of care for HFpEF, largely due to its lack of efficacy on mortality and small benefit on quality of life.

Cost-effectiveness of direct surgery versus preoperative octreotide therapy for growth-hormone secreting pituitary adenomas

PurposeThe objective of this study was to compare the cost-effectiveness of preoperative octreotide therapy followed by surgery versus the standard treatment modality for growth-hormone secreting pituitary adenomas, direct surgery (that is, surgery without preoperative treatment) from a public third-party payer perspective.MethodsWe developed an individual-level state-transition microsimulation model to simulate costs and outcomes associated with preoperative octreotide therapy followed by surgery and direct surgery for patients with growth-hormone secreting pituitary adenomas. Transition probabilities, utilities, and costs were estimated from recent published data and discounted by 3% annually over a lifetime time horizon. Model outcomes included lifetime costs [2020 United States (US) Dollars], quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs).ResultsUnder base case assumptions, direct surgery was found to be the dominant strategy as it yielded lower costs and greater health effects (QALYs) compared to preoperative octreotide strategy in the second-order Monte Carlo microsimulation. The ICER was most sensitive to probability of remission following primary therapy and duration of preoperative octreotide therapy. Accounting for joint parameter uncertainty, direct surgery had a higher probability of demonstrating a cost-effective profile compared to preoperative octreotide treatment at 77% compared to 23%, respectively.ConclusionsUsing standard benchmarks for cost-effectiveness in the US ($100,000/QALY), preoperative octreotide therapy followed by surgery may not be cost-effective compared to direct surgery for patients with growth-hormone secreting pituitary adenomas but the result is highly sensitive to initial treatment failure and duration of preoperative treatment.

Cost-effectiveness of digital therapeutics for essential hypertension

Hypertension increases the risk of cardiovascular and other diseases. Lifestyle modification is a significant component of nonpharmacological treatments for hypertension. We previously reported the clinical efficacy of digital therapeutics (DTx) in the HERB-DH1 trial. However, there is still a lack of cost-effectiveness assessments evaluating the impact of prescription DTx. This study aimed to analyze the cost-effectiveness of using prescription DTx in treating hypertension. We developed a monthly cycle Markov model and conducted Monte Carlo simulations using the HERB-DH1 trial data to investigate quality-adjusted life-years (QALYs) and the cost of DTx for hypertension plus guideline-based lifestyle modification consultation treatment as usual (TAU), comparing DTx + TAU and TAU-only groups with a lifetime horizon. The model inputs were obtained from the HERB-DH1 trial, published or publicly available data, and expert assumptions. The incremental cost-effectiveness ratio (ICER) per QALY was used as the benchmark for cost-effectiveness. We performed probabilistic sensitivity analyses (PSAs) using the Monte Carlo simulation with two million sets. The DTx + TAU strategy produced 18.778 QALYs and was associated with ¥3,924,075 ($34,122) expected costs, compared with 18.686 QALYs and ¥3,813,358 ($33,160) generated by the TAU-only strategy over a lifetime horizon, resulting in an ICER of ¥1,199,880 ($10,434)/QALY gained for DTx + TAU. The monthly cost and attrition rate of DTx for hypertension have a significant impact on ICERs. In the PSA, the probability of the DTx arm being a cost-effective option was 87.8% at a threshold value of ¥5 million ($43,478)/QALY gained. In conclusion, the DTx + TAU strategy was more cost-effective than the TAU-only strategy.

Herd Immunity Effects in Cost-Effectiveness Analyses among Low- and Middle-Income Countries.

BackgroundHerd immunity (HI) is a key benefit of vaccination programs, but the effects are not routinely included in cost-effectiveness analyses (CEAs).ObjectiveThis study investigated how the inclusion of HI in CEAs may influence the reported value of immunizations in low- and middle-income countries (LMICs) and illustrated the implications for COVID-19 immunization.MethodsWe reviewed immunization CEAs published from 2000 to 2018 focusing on LMICs using data from the Tufts Medical Center CEA Registries. We investigated the proportion of studies that included HI, the methods used, and the incremental cost-effectiveness ratios (ICERs) reported. When possible, we evaluated how ICERs would change with and without HI.ResultsAmong the 243 immunization CEAs meeting inclusion criteria, 44 studies (18%) included HI. Of those studies, 11 (25%) used dynamic transmission models, whereas the remainder used static models. Sixteen studies allowed for ICER calculations with and without HI (n = 48 ratios). The inclusion of HI always resulted in more favorable ratios. In 20 cases (42%), adding HI decreased the ICERs enough to cross at least one or more common cost-effectiveness benchmarks for LMICs. Among pneumococcal vaccination studies, including HI in the analyses decreased seven of 24 ICERs enough to cross at least one cost-effectiveness benchmark.ConclusionThe full value of immunization may be underestimated without considering a scenario in which HI is achieved. Given the evidence in pneumococcal CEAs, COVID-19 vaccine value assessments should aim to show ICERs with and without HI to inform decision-making in LMICs.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40258-021-00711-y.

Are Medical Devices Cost-Effective?

Medical devices can offer important therapeutic advances but, as for any medical interventions, there are questions about their costs and benefits. We examined health benefits and costs for pre-market approved (PMA) devices approved by the US Food and Drug Administration (FDA) (1999-2015), grouping them by generic category (e.g., drug-eluting stents) and indication. We searched PubMed for incremental health gain estimates [measured in quality-adjusted life-years (QALYs)] and incremental costs for each device category compared to previously available treatments. We calculated incremental cost-effectiveness ratios by dividing the average incremental costs by the average incremental QALY gains. In sensitivity analysis, we repeated the analysis when excluding industry-funded studies. We identified at least one relevant cost-utility or comparative-effectiveness study for 88 devices (15.9% of non-cosmetic devices approved from 1999 to 2015), and at least one device across 53 (26.2%) generic categories. The median (mean) incremental cost across generic device categories was $1701 ($13,320). The median (mean) incremental health gain across generic device categories was 0.13 (0.46) QALYs. We found that cost-effectiveness ratios for 36 of 53 (68%) and 43 of 53 (81%) device categories fell below (were more favorable than) $50,000 and $150,000 per QALY, respectively. Results were roughly similar when we excluded industry-funded studies. We found that roughly one-quarter of the major PMA medical device categories have published cost-effectiveness evidence accessible through a large, publicly available database. Available evidence suggests that devices generally offer good value, as judged relative to established cost-effectiveness benchmarks.

Switching clinic-based cervical cancer screening programs to human papillomavirus self-sampling: A cost-effectiveness analysis of vaccinated and unvaccinated Norwegian women.

Several countries have implemented primary human papillomavirus (HPV) testing for cervical cancer screening. HPV testing enables home-based, self-collected sampling (self-sampling), which provides similar diagnostic accuracy as clinician-collected samples. We evaluated the impact and cost-effectiveness of switching an entire organized screening program to primary HPV self-sampling among cohorts of HPV vaccinated and unvaccinated Norwegian women. We conducted a model-based analysis to project long-term health and economic outcomes for birth cohorts with different HPV vaccine exposure, that is, preadolescent vaccination (2000- and 2008-cohorts), multiage cohort vaccination (1991-cohort) or no vaccination (1985-cohort). We compared the cost-effectiveness of switching current guidelines with clinician-collected HPV testing to HPV self-sampling for these cohorts and considered an additional 44 strategies involving either HPV self-sampling or clinician-collected HPV testing at different screening frequencies for the 2000- and 2008-cohorts. Given Norwegian benchmarks for cost-effectiveness, we considered a strategy with an additional cost per quality-adjusted life-year below $55 000 as cost-effective. HPV self-sampling strategies considerably reduced screening costs (ie, by 24%-40% across cohorts and alternative strategies) and were more cost-effective than clinician-collected HPV testing. For cohorts offered preadolescent vaccination, cost-effective strategies involved HPV self-sampling three times (2000-cohort) and twice (2008-cohort) per lifetime. In conclusion, we found that switching from clinician-collected to self-collected HPV testing in cervical screening may be cost-effective among both highly vaccinated and unvaccinated cohorts of Norwegian women.

Is further research on adult pneumococcal vaccine uptake improvement programs worthwhile? Α value of information analysis

BackgroundPneumococcal vaccination policy for US adults is evolving, but previous research has shown that programs to increase vaccine uptake are economically favorable, despite parameter uncertainty. Using value of information (VOI) analysis and prior analyses, we examine the value of further research on vaccine uptake program parameters. MethodsIn US 50–64-year-olds, current vaccine recommendations with and without an uptake program were analyzed. In older adults, current recommendations and an alternative strategy (polysaccharide vaccine for all, adding conjugate vaccine only for the immunocompromised) with and without uptake programs were examined. Uptake program parameters were derived from a clinical trial (absolute uptake increase 12.3% [range 0–25%], per-person cost $1.78 [range $0.70–$2.26]), with other parameters obtained from US databases. VOI analyses incorporated probabilistic sensitivity analysis outputs into R-based regression techniques. ResultsIn 50–64-year-olds, an uptake program cost $54,900/QALY gained compared to no uptake program. For ages ≥65, the program cost $287,000/QALY gained with the alternative strategy and $765,000/QALY with current recommendations. In younger adults, population-level expected value of perfect information (EVPI) was $59.7 million at $50,000/QALY gained and $2.8 million at $100,000/QALY gained. In older adults, EVPI values ranged from ~$1 million to $34.5 million at $100,000 and $200,000/QALY thresholds. The population expected value of partial perfect information (EVPPI) for combined uptake program cost and uptake improvement parameters in the younger population was $368,700 at $50,000/QALY and $43,900 at $100,000/QALY gained thresholds. In older adults, population EVPPI for vaccine uptake program parameters was $0 at both thresholds, reaching a maximum value of $445,000 at a $225,000/QALY threshold. Other model parameters comprised larger components of the global EVPI. ConclusionVOI results do not support further research on pneumococcal vaccine uptake programs in adults at commonly cited US cost-effectiveness benchmarks. Further research to reduce uncertainty in other aspects of adult pneumococcal vaccination is justifiable.

PND42 COST-EFFECTIVENESS ANALYSIS OF ERENUMAB VERSUS TOPIRAMATE FOR PATIENTS WITH CHRONIC MIGRAINES TO IDENTIFY THE COST-EFFECTIVE PRICE THRESHOLD IN GREECE

Erenumab is a new preventive treatment for chronic migraine (CM) which has not yet been priced in Greece. This study evaluated the costs and outcomes of erenumab as a first-line preventative treatment for CM in Greece, compared to topiramate (TPM), an antiepileptic drug often used for CM, focusing on erenumab price thresholds required to attain cost-effectiveness benchmarks. A decision-tree model was used to project costs and outcomes, expressed as migraines avoided and as quality-adjusted life years (QALYs), from both a payer and societal perspective. The time-horizon was one year and all costs were calculated in 2018 euros (€). Sensitivity analyses assessed the impact of parameter uncertainty on model results. From an initial state of no treatment, treatment with erenumab resulted in a reduction of 12 additional migraines per year compared to the reduction for TPM. Using an erenumab price of €203/month (estimated from past pricing of analogous drugs in Greece relative to the US price of $575/month), the estimated incremental cost-effectiveness ratio (ICER) was €171 per migraine avoided and €186,813 per QALY gained, from a payer’s perspective. Accounting for both medical and non-medical costs (societal perspective), the ICERs were €163.7 per migraine avoided and €178,541 per QALY gained. Using a common existing cost-effectiveness threshold equal to three times local GDP per capita (€49,000 for Greece), for the erenumab ICER fall below this threshold, the erenumab price would have to be no more than €75 (payer perspective) or €83 (societal perspective). However, model results indicated that erenumab, as a second-line treatment for patients who fail TPM treatment, might be considered cost-effective at the €203/month price, with an ICER of €36,760 (payer perspective). Erenumab might be cost-effective as a first-line preventative treatment of CM in Greece, but only at a highly reduced price compared to the US price.

The health economics of cancer screening in Germany: Which population-based interventions are cost-effective?

Only asmall proportion of German health expenditure is spent on prevention and early detection (screening). The rationale for screening is to identify persons with disease precursors or at the early stage of diseases when they are still asymptomatic, in order to decrease disease-specific morbidity and mortality. In Germany, the economic evidence is one of the evaluation criteria for screening measures, which, among other things, takes into account the additional cost per additional case detected or per case-related event avoided, as well as acost-benefit balance.For this purpose, cost-effectiveness analyses, which report marginal or incremental cost effectiveness ratios, comparing ameasure with its appropriate alternatives, may be auseful tool. Their application requires adefensible benchmark (threshold) for cost effectiveness and asupplementary analysis of the necessary infrastructure and the budgetary impact associated with program implementation. Also (albeit not only) because of the usually long time required to observe the clinical outcomes of ascreening measure, the economic evaluation of such programs regularly involves the application of decision analytic simulation models. With regard to cancer screening programs, the available models indicate an excellent cost-benefit ratio for the fecal occult blood test and colonoscopy for colorectal cancer screening and, similarly, for the use of mammography for breast cancer screening. On the other hand, the economic evidence in favor of low-dose computed tomography for lung cancer screening does not yet appear sufficiently strong, and the currently available health economic evidence does not support the use of PSA testing for prostate screening.

Cost-Effectiveness of Cervical Cancer Screening in Women Living With HIV in South Africa: A Mathematical Modeling Study.

Women with HIV face an increased risk of human papillomavirus (HPV) acquisition and persistence, cervical intraepithelial neoplasia, and invasive cervical cancer. Our objective was to determine the cost-effectiveness of different cervical cancer screening strategies among women with HIV in South Africa. We modified a mathematical model of HPV infection and cervical disease to reflect coinfection with HIV. The model was calibrated to epidemiologic data from HIV-infected women in South Africa. Clinical and economic data were drawn from in-country data sources. The model was used to project reductions in the lifetime risk of cervical cancer and incremental cost-effectiveness ratios (ICERs) of Pap and HPV DNA screening and management algorithms beginning at HIV diagnosis, at 1-, 2-, or 3-year intervals. Strategies with an ICER below South Africa's 2016 per capita gross domestic product (US$5270) were considered "cost-effective." HPV testing followed by treatment (test-and-treat) at 2-year intervals was the most effective strategy that was also cost-effective, reducing lifetime cancer risk by 56.6% with an ICER of US$3010 per year of life saved. Other cost-effective strategies included Pap (referral threshold: HSIL+) at 1-, 2-, and 3-year intervals, and HPV test-and-treat at 3-year intervals. Pap (ASCUS+), HPV testing with 16/18 genotyping, and HPV testing with Pap or visual triage of HPV-positive women were less effective and more costly than alternatives. Considering per capita gross domestic product as the benchmark for cost-effectiveness, HPV test-and-treat is optimal in South Africa. At lower cost-effectiveness benchmarks, Pap (HSIL+) would be optimal.

Patient Variability Seldom Assessed in Cost-effectiveness Studies.

Cost-effectiveness analysis (CEA) estimates can vary substantially across patient subgroups when patient characteristics influence preferences, outcome risks, treatment effectiveness, life expectancy, or associated costs. However, no systematic review has reported the frequency of subgroup analysis in CEA, what type of heterogeneity they address, and how often heterogeneity influences whether cost-effectiveness ratios exceed or fall below conventional thresholds. We reviewed the CEA literature cataloged in the Tufts Medical Center CEA Registry, a repository describing cost-utility analyses published through 2016. After randomly selecting 200 of 642 articles published in 2014, we ascertained whether each study reported subgroup results and collected data on the defining characteristics of these subgroups. We identified whether any of the CEA subgroup results crossed conventional cost-effectiveness benchmarks (e.g., $100,000 per QALY) and compared characteristics of studies with and without subgroup-specific findings. Thirty-eight studies (19%) reported patient subgroup results. Articles reporting subgroup analyses were more likely to be US-based, government funded (v. drug industry- or nonprofit foundation-funded) studies, with a focus on primary or secondary (v. tertiary) prevention (P < 0.05 for comparisons). One or more patient characteristics were used to stratify CEA results 68 times within the 38 studies, with most stratifications using one characteristic (n = 47), most commonly age (n = 35). Among the 23 stratifications reported alongside average ratios in US studies, 13 produced subgroup ratios that crossed a conventional CEA ratio benchmark. Most CEAs do not report any subgroup results, and those that do most often stratify only by patient age. Over half of the subgroup analyses reported could lead to different value-based decision making for at least some patients.

Cost-effectiveness of maternal GBS immunization in low-income sub-Saharan Africa.

A maternal group B streptococcal (GBS) vaccine could prevent neonatal sepsis and meningitis. Its cost-effectiveness in low-income sub-Saharan Africa, a high burden region, is unknown. We used a decision tree model, with Markov nodes to project infants' lifetimes, to compare maternal immunization delivered through routine antenatal care with no immunization. 37 countries were clustered on the basis of economic and health resources and past public health performance. Vaccine efficacy for covered serotypes was ranged from 50% to 90%. The model projected EOGBS (early-onset) and LOGBS (late-onset) cases and deaths, disability-adjusted life years (DALYs), healthcare costs (2014 US$), and cost-effectiveness for a representative country in each of the four clusters: Guinea-Bissau, Uganda, Nigeria, and Ghana. Maximum vaccination costs/dose were estimated to meet two cost-effectiveness benchmarks, 0.5 GDP and GDP per capita/DALY, for ranges of disease incidence (reported and adjusted for under-reporting) and vaccine efficacy. At coverage equal to the proportion of pregnant women with≥4 antenatal visits (ANC4) and serotype-specific vaccine efficacy of 70%, maternal GBS immunization would prevent one-third of GBS cases and deaths in Uganda and Nigeria, where ANC4 is 50%, 42-43% in Guinea-Bissau (ANC4=65%), and 55-57% in Ghana (ANC4=87%). At a vaccination cost of $7/dose, maternal immunization would cost $320-$350/DALY averted in Guinea-Bissau, Nigeria, and Ghana, less than half these countries' GDP per capita. In Uganda, which has the lowest case fatality ratios, the cost would be $573/DALY. If the vaccine prevents a small proportion of stillbirths, it would be even more cost-effective. Vaccination cost/dose, disease incidence, and case fatality were key drivers of cost/DALY in sensitivity analyses. Maternal GBS immunization could be a cost-effective intervention in low-income sub-Saharan Africa, with cost-effectiveness ratios similar to other recently introduced vaccines. The vaccination cost at which introduction is cost-effective depends on disease incidence and vaccine efficacy. Clinical Trial registry name and registration number: Not applicable.

Improving pregnancy outcome in obese women: the UK Pregnancies Better Eating and Activity randomised controlled Trial

BackgroundObesity in pregnancy is associated with insulin resistance, which underpins many common complications including gestational diabetes mellitus (GDM) and fetal macrosomia.ObjectivesTo assess the effect of a complex behavioural intervention based on diet and physical activity (PA) on the risk of GDM and delivery of a large-for-gestational age (LGA) infant.DesignThree phases: (1) the development phase, (2) the pilot study and (3) a multicentre randomised controlled trial (RCT) comparing a behavioural intervention to improve glycaemic control with standard antenatal care in obese pregnant women. A cost–utility analysis was undertaken to estimate the cost-effectiveness of the health training (intervention) over and above standard care (control).SettingPilot study: antenatal clinics in four inner-city UK hospitals. RCT: eight antenatal clinics in eight UK inner-city hospitals.ParticipantsWomen were eligible for inclusion if they had a body mass index of ≥ 30 kg/m2, were pregnant with a single fetus and at 15+0to 18+6weeks’ gestation, were able to give written informed consent and were without predefined disorders.InterventionThe intervention comprised an initial session with a health trainer, followed by eight weekly sessions. Dietary advice recommended foods with a low dietary glycaemic index, avoidance of sugar-sweetened beverages and reduced saturated fats. Women were encouraged to increase daily PA.Main outcome measuresDevelopment phase: intervention development, acceptability and optimal approach for delivery. Pilot study: change in dietary and PA behaviours at 28 weeks’ gestation. RCT: the primary outcome of the RCT was, for the mother, GDM [as measured by the International Association of the Diabetes and Pregnancy Study Groups (IADPSG)’s diagnostic criteria] and, for the infant, LGA delivery (i.e. customised birthweight ≥ 90th centile for gestational age).ResultsDevelopment phase: following a literature meta-analysis, a study of dietary intention questionnaires and semistructured interviews, an intervention based on behavioural science was developed that incorporated optimal and acceptable methods for delivery. Pilot study: the pilot study demonstrated improvement in dietary behaviours in the intervention compared with the standard care arm but no increase in objectively measured PA. Process evaluation demonstrated feasibility and general acceptability. RCT: the RCT showed no effect of the intervention on GDM in obese pregnant women or the number of deliveries of LGA infants. There was a reduction in dietary glycaemic load (GL) and reduced saturated fat intake, an increase in PA and a modest reduction in gestational weight gain, all secondary outcomes. Lower than expected was the number of LGA infant deliveries in all women, which suggested that universal screening for GDM with IADPSG’s diagnostic criteria, and subsequent treatment, may reduce the number of deliveries of LGA infants. According to the cost–utility analysis, the estimated probability that the UK Pregnancies Better Eating and Activity Trial (UPBEAT) behavioural intervention is cost-effective at the £30,000/quality-adjusted life-year willingness-to-pay threshold was 1%.LimitationsIncluded the high refusal rate for participation and self-reported assessment of diet and PA.ConclusionsThe UPBEAT intervention, an intense theoretically based intervention in obese pregnant women, did not reduce the risk of GDM in women or the number of LGA infant deliveries, despite successfully reducing the dietary GL. Based on total cost to the NHS provider and health gains, the UPBEAT intervention provided no supporting evidence to suggest that the intervention represents value for money based on the National Institute for Health and Care Excellence benchmarks for cost-effectiveness.Future workAlternative strategies for reducing the risk of GDM in obese pregnant women and the number of LGA infant deliveries should be considered, including development of clinically effective interventions to prevent obesity in women of reproductive age, of clinically effective interventions to reduce weight retention following pregnancy and of risk stratification tools in early pregnancy.Trial registrationCurrent Controlled Trials ISRCTN89971375 and UK Clinical Research Network Portfolio 5035.FundingThis project was funded by the NIHR Programme Grant for Applied Research programme and will be published in full inProgramme Grants for Applied Research, Vol. 5, No. 10. See the NIHR journals library website for further project information. Contributions to funding were also provided by the Chief Scientist Office CZB/4/680, Scottish Government Health Directorates, Edinburgh; Guys and St Thomas’ Charity, Tommy’s Charity (Lucilla Poston, Annette L Briley, Paul T Seed) and the NIHR Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, UK and the Academy of Finland, Finland. Keith M Godfrey was supported by the National Institute for Health Research through the NIHR Southampton Biomedical Research Centre. Lucilla Poston and Keith M Godfrey were supported by the European Union’s Seventh Framework Programme (FP7/2007-2013), project EarlyNutrition under grant agreement number 289346.

Economic Analysis of Apixaban Therapy for Patients With Atrial Fibrillation From a US Perspective

The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial reported that apixaban therapy was superior to warfarin therapy in preventing stroke and all-cause death while causing significantly fewer major bleeds. To establish the value proposition of substituting apixiban therapy for warfarin therapy in patients with atrial fibrillation, we performed a cost-effectiveness analysis using patient-level data from the ARISTOTLE trial. To assess the cost and cost-effectiveness of apixaban therapy compared with warfarin therapy in patients with atrial fibrillation from the perspective of the US health care system. This economic analysis uses patient-level resource use and clinical data collected in the ARISTOTLE trial, a multinational randomized clinical trial that observed 18 201 patients (3417 US patients) for a median of 1.8 years between 2006 and 2011. Apixaban therapy vs warfarin therapy. Within-trial resource use and cost were compared between treatments, using externally derived US cost weights. Life expectancies for US patients were estimated according to their baseline risk and treatment using time-based and age-based survival models developed using the overall ARISTOTLE population. Quality-of-life adjustment factors were obtained from external sources. Cost-effectiveness (incremental cost per quality-adjusted life-year gained) was evaluated from a US perspective, and extensive sensitivity analyses were performed. Of the 3417 US patients enrolled in ARISTOTLE, the mean (SD) age was 71 (10) years; 2329 (68.2%) were male and 3264 (95.5%) were white. After 2 years of anticoagulation therapy, health care costs (excluding the study drug) of patients treated with apixaban therapy and warfarin therapy were not statistically different (difference, -$60; 95% CI, -$2728 to $2608). Life expectancy, modeled from ARISTOTLE outcomes, was significantly longer with apixaban therapy vs warfarin therapy (7.94 vs 7.54 quality-adjusted life years). The incremental cost, including cost of anticoagulant and monitoring, of achieving these benefits was within accepted US norms ($53 925 per quality-adjusted life year, with 98% likelihood of meeting a $100 000 willingness-to-pay threshold). Results were generally consistent when model assumptions were varied, with lifetime cost-effectiveness most affected by the price of apixaban and the time horizon. Apixaban therapy for ARISTOTLE-eligible patients with atrial fibrillation provides clinical benefits at an incremental cost that represents reasonable value for money judged using US benchmarks for cost-effectiveness. clinicaltrials.gov Identifier: NCT00412984.

Economic Evaluation of Family Planning Interventions in Low and Middle Income Countries; A Systematic Review.

BackgroundA significant number of women in low and middle income countries (L-MICs) who need any family planning, experience a lack in access to modern effective methods. This study was conducted to review potential cost effectiveness of scaling up family planning interventions in these regions from the published literatures and assess their implication for policy and future research.Study designA systematic review was performed in several electronic databases i.e Medline (Pubmed), Embase, Popline, The National Bureau of Economic Research (NBER), EBSCOHost, and The Cochrane Library. Articles reporting full economic evaluations of strategies to improve family planning interventions in one or more L-MICs, published between 1995 until 2015 were eligible for inclusion. Data was synthesized and analyzed using a narrative approach and the reporting quality of the included studies was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement.ResultsFrom 920 references screened, 9 studies were eligible for inclusion. Six references assessed cost effectiveness of improving family planning interventions in one or more L-MICs, while the rest assessed costs and consequences of integrating family planning and HIV services, concerning sub-Saharan Africa. Assembled evidence suggested that improving family planning interventions is cost effective in a variety of L-MICs as measured against accepted international cost effectiveness benchmarks. In areas with high HIV prevalence, integrating family planning and HIV services can be efficient and cost effective; however the evidence is only supported by a very limited number of studies. The major drivers of cost effectiveness were cost of increasing coverage, effectiveness of the interventions and country-specific factors.ConclusionImproving family planning interventions in low and middle income countries appears to be cost-effective. Additional economic evaluation studies with improved reporting quality are necessary to generate further evidence on costs, cost-effectiveness, and affordability, and to support increased funding and investments in family planning programs.

Cost-Effectiveness Analysis of Radiation Therapy Versus Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma

The objective of this study was to compare the cost-effectiveness of transoral robotic surgery (TORS) versus the standard treatment modality for oropharyngeal squamous cell carcinoma (OPSCC), radiation therapy (RT), in a subset of patients with early-stage OPSCC. We developed a microsimulation state-transition model associated with RT and TORS for patients with clinically staged T1N0M0 to T2N1M0 OPSCC.Transition probabilities, utilities, and costs for each health state were estimated from recently published data and discounted by 3% annually over a lifetime time horizon. Model outcomes included lifetime costs (in 2014 US dollars), health benefits (quality-adjusted life-years [QALYs]), and cost-effectiveness ratios from a societal perspective. Under base-case assumptions, TORS was associated with modest gains in QALYs. RT yielded 10.43 QALYs at a cost of $123,410 per patient, whereas TORS yielded 11.10 QALYs at a cost of $178,480. This resulted in an incremental cost-effectiveness ratio of $82,190/QALY gained. The incremental cost-effectiveness ratio was most sensitive to the need for adjuvant therapy, cost of late toxicity, age at diagnosis, disease state utilities, and discount rate. Accounting for joint parameter uncertainty, RT had a higher probability of demonstrating a cost-effective profile compared with TORS, at 54% compared with 46%. By use of standard benchmarks for cost-effectiveness in the United States, TORS may be a cost-effective alternative for the subset of patients with early-stage OPSCC but demonstrates considerable sensitivity to assumptions around quality of life.

What Pertussis Mortality Rates Make Maternal Acellular Pertussis Immunization Cost-Effective in Low- and Middle-Income Countries? A Decision Analysis.

Background. Despite longstanding infant vaccination programs in low- and middle-income countries (LMICs), pertussis continues to cause deaths in the youngest infants. A maternal monovalent acellular pertussis (aP) vaccine, in development, could prevent many of these deaths. We estimated infant pertussis mortality rates at which maternal vaccination would be a cost-effective use of public health resources in LMICs.Methods. We developed a decision model to evaluate the cost-effectiveness of maternal aP immunization plus routine infant vaccination vs routine infant vaccination alone in Bangladesh, Nigeria, and Brazil. For a range of maternal aP vaccine prices, one-way sensitivity analyses identified the infant pertussis mortality rates required to make maternal immunization cost-effective by alternative benchmarks ($100, 0.5 gross domestic product [GDP] per capita, and GDP per capita per disability-adjusted life-year [DALY]). Probabilistic sensitivity analysis provided uncertainty intervals for these mortality rates.Results. Infant pertussis mortality rates necessary to make maternal aP immunization cost-effective exceed the rates suggested by current evidence except at low vaccine prices and/or cost-effectiveness benchmarks at the high end of those considered in this report. For example, at a vaccine price of $0.50/dose, pertussis mortality would need to be 0.051 per 1000 infants in Bangladesh, and 0.018 per 1000 in Nigeria, to cost 0.5 per capita GDP per DALY. In Brazil, a middle-income country, at a vaccine price of $4/dose, infant pertussis mortality would need to be 0.043 per 1000 to cost 0.5 per capita GDP per DALY.Conclusions. For commonly used cost-effectiveness benchmarks, maternal aP immunization would be cost-effective in many LMICs only if the vaccine were offered at less than $1–$2/dose.

CP2 - Interventions For Ultra-Rare Disorders (Urds) And The Logic Of Cost Effectiveness

Background: In many cases, medicines for ultra-rare disorders (URDs) have high acquisition costs and are associated with incremental cost per quality-adjusted life year (QALY) gained exceeding widely used benchmarks for cost effectiveness. Objectives: To address the underlying reasons why interventions for URDs often fail to meet conventional benchmarks for cost effectiveness and deliberate implications for formal Health Technology Assessments (HTAs) including economic evaluation. Methods: An international group of experts in health economics, medical ethics, evidence-based medicine (EBM), and HTA met in conjunction with the Annual European ISPOR Congresses in November 2012, 2013, and 2014. Results: In contrast to the principles of EBM, the logic of cost effectiveness (including benchmarks for incremental cost per QALY gained, as applied by some HTA agencies as a measure of “value for money”) does not adequately capture well-established social norms and preferences regarding health care resource allocation. Such preferences include, but are not limited to, a priority for care for the worst off (related to initial health state), for those with more urgent conditions (the so called “rule of rescue”), and a relatively lower priority based upon capacity to benefit, as well as a dislike against “all or nothing” resource allocation decisions that might deprive certain groups of patients from any chance to access effective care. Conclusions: The group concluded that there exists a strong need for an improved or new paradigm to assess value for money. Candidates include direct social value measurement using the relative social willingness-to-pay or person trade-off instruments, combined with a greater role for budget impact analysis. As a pragmatic interim alternative, multi-criteria decision analysis may prove useful. Further systematic research into social preferences, including their valid measurement, should be prioritized relative to the continued application of a descriptively flawed framework based on benchmarks for maximum incremental cost per QALY gained.

Cost-Effectiveness of Femtosecond Laser-Assisted Cataract Surgery versus Phacoemulsification Cataract Surgery

To perform a comparative cost-effectiveness analysis (CEA) of femtosecond laser-assisted cataract surgery (LCS) and conventional phacoemulsification cataract surgery (PCS) DESIGN: Retrospective CEA using computer-based econometric modeling. Hypothetical cohort of patients undergoing cataract surgery in the better eye based on a review of the current literature and our direct experience using LCS. A cost-effectiveness decision tree model was constructed to analyze the cost-effectiveness of LCS compared with PCS. Complication rates of cataract surgery were obtained from a review of the current literature to complete the cohort of patients and outcomes. This data was incorporated with time trade-off utility values converted from visual acuity outcomes. Improvements in best-corrected visual acuity obtained from the literature were used to calculate the increase in quality-adjusted life-years (QALYs) in a hypothetical cohort between 6 months and 1 year after cataract surgery. This was combined with approximate costs in a cost-utility analysis model to determine the incremental cost-effectiveness ratios (ICERs). Based on the simulated complication rates of PCS and LCS and assuming resultant visual acuity outcome improvement of 5% in uncomplicated cases of LCS, the cost-effectiveness (dollars spent per QALY) gained from LCS was not cost-effective at $92 862 Australian Dollars. The total QALY gain for LCS over PCS was 0.06 units. Multivariate sensitivity analyses revealed that LCS would need to significantly improve visual outcomes and complications rates over PCS, along with a reduction in cost to patient, to improve cost effectiveness. Modeling a best-case scenario of LCS with excellent visual outcomes (100%), a significant reduction in complications (0%) and a significantly reduced cost to patient (of $300) resulted in an ICER of $20 000. Laser cataract surgery, irrespective of potential improvements in visual acuity outcomes and complication rates, is not cost effective at its current cost to patient when compared with cost-effectiveness benchmarks and other medical interventions, including PCS. A significant reduction in the cost to patient (via reduced consumable/click cost) would increase the likelihood of LCS being considered cost effective.