Quality-adjusted Life Year Ratio Research Articles

Cost-Effectiveness of Nonoperative Management vs Upfront Laparoscopic Appendectomy for Pediatric Uncomplicated Appendicitis Over 1 Year.

Non-operative management (NOM) with antibiotics alone for pediatric uncomplicated appendicitis is accepted to be safe and effective. However, the relative cost-effectiveness of this approach compared to appendectomy remains unknown. We aimed to evaluate the cost-effectiveness of non-operative versus operative management for pediatric uncomplicated acute appendicitis. A trial-based real-world economic evaluation from the healthcare sector perspective was performed using data collected from a multi-institutional non-randomized controlled trial investigating NOM versus surgery. The time horizon was 1 year, with costs in 2023 US dollars. Ratio of costs-to-charges (RCC)-based data for the initial hospitalization, readmissions, and unplanned emergency department visits were extracted from the Pediatric Health Information System (PHIS). Utility data were derived from patient-reported disability days and health-related quality-of-life scores. Multiple scenarios and one-way deterministic and probabilistic sensitivity analyses accounted for parameter uncertainty. Willingness-to-pay (WTP) threshold was set at $100,000 per quality-adjusted life year (QALY) or disability-adjusted life year (DALY). Primary outcome measures included total and incremental mean costs, QALY, DALY, and incremental cost-effectiveness ratios (ICERs). Of 1,068 participants, 370 (35%) selected NOM and 698 (65%) selected urgent laparoscopic appendectomy. Operative management cost an average of $9,791/patient and yielded an average of 0.884 QALYs while NOM cost an average of $8,044/patient and yielded an average of 0.895 QALYs. NOM was both less costly and more effective in base case and scenario analyses using disability days and alternate methods of calculating utilities. NOM is cost-effective compared to laparoscopic appendectomy for pediatric uncomplicated appendicitis over 1 year.

Cost effectiveness analysis of nadofaragene firadenovec for the treatment of high-risk, bacillus Calmette-Guerin–unresponsive, non-muscle invasive bladder cancer from a US third-party payer perspective.

4598 Retraction The abstract by Yang et al entitled, “Cost effectiveness analysis of nadofaragene firadenovec for the treatment of high-risk, bacillus Calmette-Guerin–unresponsive, non-muscle invasive bladder cancer from a US third-party payer perspective,” ( Journal of Clinical Oncology 42, no. 16_suppl 4598; DOI 10.1200/JCO.2024.42.16_suppl.4598) published on May 29, 2024, has been retracted. The authors wish to retract this article as it is undergoing additional review and further updates are expected. They could not rule out that the current results may be incorrect, inaccurate, or misleading. It is important to provide the best estimate of nadofaragene’s cost effectiveness vs pembrolizumab in this space for healthcare decision making whereas uncertainty remains at this time. The authors are no longer able to endorse the work. This abstract was retracted on August 26, 2024. Background: Bladder cancer is the second most common cancer in the urinary tract in the United States (US), with 75% restricted to the superficial layers of the bladder and termed as non-muscle invasive bladder cancer (NMIBC). Bacillus Calmette-Guerin (BCG) is the standard of care for high risk NMIBC patients; however, bladder preserving treatments are limited after BCG failure. Nadofaragene firadenovec, an interferon-alfa-2b encoding gene therapy, is approved for the treatment of high-risk BCG-unresponsive NMIBC with carcinoma in situ (CIS) with or without papillary tumors (CIS ± Ta/T1). This study assessed cost-effectiveness of nadofaragene firadenovec compared to pembrolizumab from a US third-party payer perspective. Methods: A Markov model was developed to estimate total costs, quality-adjusted life-years (QALYs), and corresponding incremental cost per QALY ratios (ICER) over a lifetime time horizon for patients treated with nadofaragene firadenovec or pembrolizumab. In the absence of head-to-head data comparing nadofaragene firadenovec to pembrolizumab, the model population was based on Phase 3 trial for nadofaragene firadenovec (NCT02773849, data cut: July 8, 2019) and included adult patients (mean age of 71.0 years; 11.7% female) with high-risk, BCG unresponsive NMIBC with CIS ± Ta/T1. Pembrolizumab data was informed by the published KeyNote-057 trial (NCT02625961, data-cut: May 25, 2020). The model consisted of 7 mutually exclusive health states with a three-month model cycle: NMIBC disease-free, NMIBC recurrence, MIBC, metastatic disease, cystectomy, post-cystectomy, and death. Drug costs, adverse events (AEs) costs, and health state associated medical costs were included and discounted at 3% annually. The nadofaragene firadenovec and pembrolizumab prices were informed by 2023 U.S. pricing compendia. Sensitivity analyses were performed. Results: Compared to pembrolizumab, nadofaragene firadenovec resulted in an ICER of $123,725 per QALY gained. The incremental cost was $24,194 (nadofaragene firadenovec: $374,280; pembrolizumab: $350,086) and the incremental QALYs were 0.196 (nadofaragene firadenovec: 4.560; pembrolizumab: 4.364). The cumulative drug acquisition and administration costs for nadofaragene firadenovec and pembrolizumab were $181,134 and $141,954 respectively, and AE costs were $248 and $2,749 and medical costs associated with health states were $192,898 and $205,382, respectively. The ICERs for nadofaragene firadenovec remained cost-effective across a majority of the sensitivity analyses and simulations. Conclusions: The analysis suggests that nadofaragene firadenovec is cost-effective compared to pembrolizumab for the treatment of high-risk, BCG unresponsive NMIBC with CIS ± Ta/T1 at a willingness to pay of $150,000/QALY.

Effectiveness and cost-effectiveness analysis of 11 treatment paths, seven first-line and three second-line treatments for Chinese patients with advanced wild-type squamous non-small cell lung cancer: A sequential model.

A total of 11 treatment sequences for advanced wild-type squamous non-small cell lung cancer are recommended by Chinese Society of Clinical Oncology Guidelines, consisting of seven first-line and three second-line treatments. Five of these treatments were newly approved in China between 2021 and 2022. We evaluated the effectiveness and cost-effectiveness of these strategies from the Chinese healthcare system perspective. Network meta-analysis with non-proportional hazards was used to calculate the relative efficacy between interventions. A sequential model was developed to estimate costs and quality-adjusted life years (QALY) for treatment sequences with first-line platinum- and paclitaxel-based chemotherapy (SC) with or without nedaplatin, tislelizumab, camrelizumab, sintilimab, sugemalimab or pembrolizumab, followed by second-line docetaxel, tislelizumab or nivolumab. SC and docetaxel were used as comparators for first-line and second-line treatments, respectively. QALY and incremental cost-effectiveness ratio (ICER) were used to evaluate effectiveness and cost-effectiveness, respectively. Cost-effective threshold was set as USD 19,091. Subgroup analysis was conducted to determine the best first-line and second-line therapy. Pembrolizumab + SC, followed by docetaxel (PED) was the most effective treatment sequence. QALYs for patients received SC, nedaplatin + SC, tislelizumab + SC, sintilimab + SC, camrelizumab + SC, sugemalimab + SC, pembrolizumab + SC followed by docetaxel were 0.866, 0.906, 1.179, 1.266, 1.179, 1.266, 1.603, 1.721, 1.807; QALYs for SC, nedaplatin + SC followed by tislelizumab were 1.283, 1.301; QALYs for SC, nedaplatin + SC followed by nivolumab were 1.353, 1.389. Camrelizumab + SC, followed by docetaxel (CAD) was the most cost-effective. Compared to SC with or without nedaplatin, tislelizumab, or sintilimab followed by docetaxel, ICERs of CAD were USD 12,276, 13,210, 6,974, 9,421/QALY, respectively. Compared with nedaplatin or SC followed by tislelizumab, the ICERs of CAD were USD 4,183, 2,804/QALY; CAD was dominant compared with nedaplatin or SC followed by nivolumab; The ICER of sugemalimab + SC followed by docetaxel and PED were USD 522,023, 481,639/QALY compared with CAD. Pembrolizumab + SC and camrelizumab + SC were the most effective and cost-effective first-line options, respectively; tislelizumab was the most effective and cost-effective second-line therapy. Tislelizumab used in second-line was more effective than first-line, no significant differences between their cost-effectiveness. Sensitivity and scenario analysis confirmed robustness of the results. PED and CAD are the most effective and cost-effective treatment sequence, respectively; pembrolizumab + SC and camrelizumab + SC are the most effective and cost-effective first-line choice, respectively; tislelizumab is the most effective and cost-effective second-line choice.

Cost-Effectiveness Analysis of Minimally Invasive Trabecular Meshwork Stents with Phacoemulsification

To investigate the costs and effects of implanting trabecular meshwork bypass stents during cataract surgery from a societal perspective in the United States. Cost-utility analysis using Markov models and efficacy/safety data from published pivotal or randomized control trials (RCTs) of devices investigated. Patients aged 65 years and older with mild to moderate primary open-angle glaucoma with or without visually significant cataract. With the use of Markov models, glaucoma progression through 4 glaucoma states (mild, moderate, advanced, severe/blind) and death were simulated over 35 years. The cohort with cataract entered the model and received cataract surgery with or without device implantation. We included a medication management only reference group to calculate total costs and outcomes for those without cataract. Intraocular pressure (IOP) reductions from RCTs were converted to glaucoma state transition probabilities using visual field (VF) mean deviation (MD) decline rates from the Early Manifest Glaucoma Trial. Progressive thinning of the retinal nerve fiber layer (RNFL) on OCT imaging related to IOP control warranted further intervention, including adding medication, selective laser trabeculoplasty (SLT), or incisional glaucoma surgery. We estimated whole costs at Medicare rates and obtained utility values for glaucoma states from previous studies. Incremental costs per quality-adjusted life-year (QALY) gained were evaluated at a QALY threshold of $50 000. One-way deterministic sensitivity analysis, scenario analyses, and probabilistic sensitivity analyses addressed parameter uncertainty and demonstrated model robustness. Total costs, QALY, and incremental cost-effectiveness ratio (ICER). Over 35 years in the base case, the Hydrus (Ivantis, Inc.) implanted with cataract surgery arm cost $48 026.13 and gained 12.26 QALYs. The iStent inject (Glaukos Corp.) implanted with cataract surgery arm cost $49 599.86 and gained 12.21 QALYs. Cataract surgery alone cost $54 409.25 and gained 12.04 QALYs. Initial nonsurgical management cost $57 931.22 and gained 11.74 QALY. The device arms dominated or were cost-effective compared with cataract surgery alone within 5 years and throughout sensitivity analyses. The iStent inject arm was cost-effective in 94.19% of iterations in probabilistic sensitivity analyses, whereas the Hydrus arm was cost-effective in 94.69% of iterations. Implanting the Hydrus Microstent or iStent inject during cataract surgery is cost-effective at a conservative QALY threshold.

Toward Better Data Dashboards for US Drug Value Assessments

ObjectivesTo explore the use of data dashboards to convey information about a drug’s value, and reduce the need to collapse dimensions of value to a single measure. MethodsReview of the literature on US Drug Value Assessment Frameworks, and discussion of the value of data dashboards to improve the manner in which information on value is displayed. ResultsThe incremental cost per quality-adjusted life-year ratio is a useful starting point for conversation about a drug’s value, but it cannot reflect all of the elements of value about which different audiences care deeply. Data dashboards for drug value assessments can draw from other contexts. Decision makers should be presented with well-designed value dashboards containing various metrics, including conventional cost per quality-adjusted life-year ratios as well as measures of a drug’s impact on clinical and patient-centric outcomes, and on budgetary and distributional consequences, to convey a drug’s value along different dimensions. ConclusionsThe advent of US drug value frameworks in health care has forced a concomitant effort to develop appropriate information displays. Researchers should formally test different formats and elements.

Cost-Effectiveness Analysis from a Randomized Controlled Trial of Tailored Exercise Prescription for Women with Breast Cancer with 8-Year Follow-Up.

Studies show conflicting results on whether exercise interventions to improve outcomes for women with breast cancer are cost-effective. We modelled the long-term cost-effectiveness of the Exercise for Health intervention compared with usual care. A lifetime Markov cohort model for women with early breast cancer was constructed taking a societal perspective. Data were obtained from trial, epidemiological, quality of life, and healthcare cost reports. Outcomes were calculated from 5000 Monte Carlo simulations, and one-way and probabilistic sensitivity analyses. Over the cohort’s remaining life, the incremental cost for the exercise versus usual care groups were $7409 and quality-adjusted life years (QALYs) gained were 0.35 resulting in an incremental cost per QALY ratio of AU$21,247 (95% Uncertainty Interval (UI): Dominant, AU$31,398). The likelihood that the exercise intervention was cost-effective at acceptable levels was 93.0%. The incremental cost per life year gained was AU$8894 (95% UI Dominant, AU$11,769) with a 99.4% probability of being cost effective. Findings were most sensitive to the probability of recurrence in the exercise and usual care groups, followed by the costs of out-of-pocket expenses and the model starting age. This exercise intervention for women after early-stage breast cancer is cost-effective and would be a sound investment of healthcare resources.

Cost-Effectiveness Threshold of Magnetic Resonance Image-Guided Radiotherapy for Localized Prostate Cancer

Magnetic resonance image guided radiotherapy (MR-IGRT) is anticipated to reduce toxicity through intrafraction motion detection and smaller treatment margins, but no studies have assessed if the technology can be cost-effective. Our purpose is to determine if MR-IGRT for treatment of localized prostate cancer can achieve cost-effectiveness through toxicity reduction alone compared to CT-based image guided radiotherapy (CT-IGRT). The comparison groups were MR-IGRT and CT-IGRT delivered in conventional 39 fraction and stereotactic body radiotherapy (SBRT) 5 fraction schedules. To determine the cost of delivering radiotherapy to each group, time driven activity-based costing was used with a healthcare cost perspective. Equipment and therapy-related costs for each group were calculated with data from two institutions and literature values assuming a 15-year lifespan per machine and utilization of treatment machines 8 hours/day, 5 days/week, 50 weeks/year. The gastrointestinal and genitourinary toxicity rates associated with CT-IGRT in this model were averaged from 20 prior studies. The costs and utilities associated with various health states were obtained from literature values and cost databases. Markov modeling was used to determine the costs and quality adjusted life years (QALYs) saved with each 1% relative reduction in acute and chronic toxicities by MR-IGRT over 15 years with a discount rate of 3%. Toxicity reduction thresholds for cost-effectiveness were then calculated based on the added cost of MR-IGRT juxtaposed with the cost reduction and QALYs saved for each 1% relative toxicity reduction from Markov modeling. One-way sensitivity analyses were performed. Standard $50,000 and $100,000 per QALY ratios were used. The added cost of MR-IGRT over CT-IGRT was $1,459 per course of SBRT and $10,129 per course of conventionally fractionated radiotherapy. Relative toxicity reductions of 7% and 14% were required for MRI-guided SBRT to be cost-effective compared to CT-guided SBRT using $100,000 and $50,000 per QALY, respectively. MR-IGRT in conventional fractionation required relative toxicity reductions of 50% and 94% to be cost-effective at $100,000 and $50,000 per QALY. In the sensitivity analyses, the cost-effectiveness of MR-IGRT was most dependent on the number of patients treated on the MR-IGRT and CT-IGRT systems as well as the initial and maintenance costs of the MR-IGRT system. From a healthcare perspective, MR-IGRT can be cost-effective through toxicity reduction alone. Hypofractionated schedules, such a five fraction SBRT, are most likely to achieve cost-effectiveness as they require only slight reductions in toxicity (7-14%).

Economic evaluation of 'Men on the Move', a 'real world' community-based physical activity programme for men.

Physical activity (PA) interventions capable of producing health benefits cost effectively are a public health priority across the Western world. 'Men on the Move' (MOM), a community-based PA intervention for men, demonstrated significant health benefits up to 52-weeks (W) post-baseline. This article details the economic evaluation of MOM with a view to determining its cost-effectiveness as a public health intervention to be rolled out nationally in Ireland. Cost-effectiveness was determined by comparing the costs (direct and indirect) of the programme to its benefits, which were captured as the impact on quality-adjusted life-years (QALYs). For the benefits, cost-utility analysis was conducted by retrospectively adapting various health-related measures of participants to generate health states using Brazier et al.'s (2002) short form-6D algorithm. This in turn allowed for 'utility measures' to be generated, from which QALYs were derived. Findings show MOM to be cost-effective in supporting an 'at risk' cohort of men achieves significant improvements in aerobic fitness, weight loss and waist reduction. The total cost per participant (€125.82 for each of the 501 intervention participants), the QALYs gained (11.98 post-12-W intervention, or 5.3% health improvement per participant) and estimated QALYs ratio costs of €3723 represents a cost-effective improvement when compared to known QALY guidelines. The analysis shows that the cost per QALY achieved by MOM is significantly less than the existing benchmarks of £20000 and €45000 in the UK and Ireland respectively, demonstrating MOM to be cost-effective.

Toxicity reduction required for MRI-guided radiotherapy to be cost-effective in the treatment of localized prostate cancer.

To determine the toxicity reduction required to justify the added costs of MRI-guided radiotherapy (MR-IGRT) over CT-based image guided radiotherapy (CT-IGRT) for the treatment of localized prostate cancer. The costs of delivering prostate cancer radiotherapy with MR-IGRT and CT-IGRT in conventional 39 fractions and stereotactic body radiotherapy (SBRT) 5 fractions schedules were determined using literature values and cost accounting from two institutions. Gastrointestinal and genitourinary toxicity rates associated with CT-IGRT were summarized from 20 studies. Toxicity-related costs and utilities were obtained from literature values and cost databases. Markov modeling was used to determine the savings per patient for every 1% relative reduction in acute and chronic toxicities by MR-IGRT over 15 years. The costs and quality adjusted life years (QALYs) saved with toxicity reduction were juxtaposed with the cost increase of MR-IGRT to determine toxicity reduction thresholds for cost-effectiveness. One way sensitivity analyses were performed. Standard $100,000 and $50,000 per QALY ratios were used. The added cost of MR-IGRT was $1,459 per course of SBRT and $10,129 per course of conventionally fractionated radiotherapy. Relative toxicity reductions of 7 and 14% are required for SBRT to be cost-effective using $100,000 and $50,000 per QALY, respectively. Conventional radiotherapy requires relative toxicity reductions of 50 and 94% to be cost-effective. From a healthcare perspective, MR-IGRT can reasonably be expected to be cost-effective. Hypofractionated schedules, such a five fraction SBRT, are most likely to be cost-effective as they require only slight reductions in toxicity (7-14%). This is the first detailed economic assessment of MR-IGRT, and it suggests that MR-IGRT can be cost-effective for prostate cancer treatment through toxicity reduction alone.

The integrated care pathway for managing post stroke patients (iCaPPS\xa9) in public primary care Healthcentres in Malaysia: impact on quality adjusted life years (QALYs) and cost effectiveness analysis

BackgroundThe delivery of post stroke care is fragmented even in advanced public healthcare systems, globally. Primary care teams are entrusted to provide longer term care for stroke survivors in most developing countries. The integrated Care Pathway for Post Stroke patients (iCaPPS©) was designed to guide primary care teams to incorporate further rehabilitation and regular screening for post stroke complications among patients residing at home in communities, using the shared-care approach, especially in areas with limited access to specialist stroke care services. The iCaPPS© addressed coordination of rehabilitation and screening for post stroke complications which were absent in the current conventional care of patients managed at public primary care healthcentres. This study aimed to evaluate the cost effectiveness and impact of iCaPPS© on quality-adjusted- life-years (QALY) compared with current conventional monitoring at public primary care healthcentres.MethodsA pragmatic healthcentre-based cluster randomised controlled trial-within trial on 151 post stroke patients from 10 public primary care facilities in Peninsular Malaysia was conducted to evaluate QALY of patients managed with iCaPPS© (n = 86) vs conventional care (n = 65) for 6 months. Costs from societal perspective were calculated, using combination of top down and activity-based costing methods. The 5-level EQ5D (EQ-5D-5 L) was used to calculate health state utility scores. Cost per QALY and incremental cost effectiveness ratio (ICER) were determined. Differences within groups were determined using Mann-Whitney tests.ResultsTotal costs for 6 months treatment with iCaPPS© was MYR790.34, while conventional care cost MYR527.22. Median QALY for iCaPPS© was 0.55 (0,1.65) compared to conventional care 0.32 (0, 0.73) (z = − 0.21, p = 0.84). Cost per QALY for iCaPPS© was MYR1436.98, conventional care was MYR1647.56. The ICER was MYR1144.00, equivalent to 3.7% of per capita GDP (2012 prices).ConclusionsManagement of post stroke patients in the community using iCaPPS© costs less per QALY compared to current conventional care and is very cost effective.Trial registrationTrial Registration number ACTRN12616001322426. Registered 21 September 2016. (Retrospectively registered).

Using information on ART costs and benefits to mobilise resources – comparing different methods and contexts

Sustaining HIV and AIDS responses depends on a mix of donor, government and private funders. Their decisions about investing in HIV treatment may be informed by various types of economic evaluations, which may be more or less useful for different contexts. This paper benchmarks methods against each other. Epidemiological and demographic impacts of HIV and antiretroviral therapy (ART) from 1996–2015 were quantified using country- specific spectrum files. The study compared societal benefits of ART using the full income (FI) methodology with “conventional” benefit, utility and effectiveness estimates produced with the same data. The FI estimates suggested $3.50 in benefits per dollar spent on ART globally, 2.6 times larger than productivity-related measures of benefits, of $1.33 in benefits per dollar. Higher benefit-cost ratios are mainly because FI reflects value of life beyond what people produce at work and in non-working age groups, and allocates the future stream of benefits in the year that death is avoided. ART costs were 0.78 times per capita GDP per quality-adjusted life-years gained globally. FI benefit-cost ratios are considerably higher in upper- and lower-middle-income countries than in low- or high-income countries. Productivity-based benefits also exceeded costs in all but one region but had smaller ratios and different regional patterns. Per capita GDP per quality-adjusted life-years ratios were below 1.2 for all regions and country income bands, suggesting cost effectiveness. The fact that FI returns of ART are higher than productivity returns, helps to quantify developmental benefits of interventions that directly extend life and its quality, arguably the objective of development. They provide an important argument to increase budget allocations to health sectors for ART scale-up, and not just reallocate existing health resources. Benchmarking FI returns against cost per quality- adjusted life-years may allow comparison to other “cost effective” health interventions. However, caution should be taken in extrapolations between measures, because they produce different rankings across country categories.

Cost-Effectiveness of Dolutegravir as a First-Line Treatment Option in the HIV-1–Infected Treatment-Naive Patients in Russia

To evaluate the cost effectiveness of dolutegravir + abacavir/lamivudine (DTG + ABC/3TC) compared with raltegravir + abacavir/lamivudine (RAL + ABC/3TC) and ritonavir-boosted darunavir + abacavir/lamivudine (DRV/r + ABC/3TC) in HIV-1-infected treatment-naive patients in Russia. A dynamic Markov model was developed with five response states and six CD4+-based health states. Efficacy estimated as probability of viral suppression (HIV RNA <50 copies/ml) at 48 weeks was obtained from a published network meta-analysis. Baseline cohort characteristics and health state utilities were informed using DTG phase 3 clinical trials. Health care resource use was obtained from literature and costed using published unit costs. Costs (presented in Russian rubles) included antiretroviral drug costs; HIV management costs such as routine care; costs of treating cardiovascular conditions, opportunistic infections, and drug-related adverse effects; and mortality costs. A patient lifetime analysis was conducted using the societal perspective. Outcomes were quality-adjusted life-years (QALYs), life-years, incremental cost per QALY ratio, and incremental cost per responder. The viral suppression rate among patients receiving DTG + ABC/3TC was 71.7% compared with 65.2% for RAL + ABC/3TC and 59.6% for DRV/r + ABC/3TC. The mean duration of response per patient was 116.6 months for DTG + ABC/3TC, 108.6 months for RAL + ABC/3TC, and 98.9 months for DRV/r + ABC/3TC. Total discounted costs for treatment over patient lifetime were RUB 2.89, 5.32, and 4.38 million for DTG + ABC/3TC, RAL + ABC/3TC, and DRV/r + ABC/3TC, respectively. Lifetime discounted QALYs were 12.73 for patients on DTG + ABC/3TC and 12.72 each for patients on RAL + ABC/3TC and DRV/r + ABC/3TC. DTG + ABC/3TC thus dominated the other two alternatives. With lower costs, higher response rates, and comparable QALYs, DTG + ABC/3TC can be considered as a cost-effective alternative.

Long-term clinical outcomes and economic evaluation of the ketogenic diet versus care as usual in children and adolescents with intractable epilepsy

ObjectiveTo examine long-term retention rate, clinical outcomes, cost-utility and cost-effectiveness of the Ketogenic Diet (KD) compared with care as usual (CAU) in children and adolescents with intractable epilepsy from a societal perspective. MethodsParticipants were randomized into a KD or CAU group. Seizure frequency, quality adjusted life years (QALYs), side-effects, seizure severity, health care costs, production losses, patient and family costs were assessed at baseline and during 16-months of follow-up. Incremental cost-effectiveness ratios (ICERs) (i.e. cost per QALY and cost per responder) and cost-effectiveness acceptability curves are presented. Results48 children were included in the analyses of this study (26 from KD group). In total, 58% of the KD group completed the follow-up of 16 months; 11 dropped-out for various reasons. At 16 months, 35% of the KD participants had a seizure reduction≥50% from baseline, compared with 18% of the CAU participants. Mean costs per patient in the CAU group were €53,367 (extrapolated) compared to €61,019 per patient in the KD group, resulting in an ICER of €46,564 per responder. Cost per QALY rose well above any acceptable ceiling ratio. At 4-months’ follow-up, the KD group showed significantly more gastro-intestinal problems compared to the CAU group. At 16 months, the KD group reported fewer problems compared to CAU. Furthermore, 46.2% of the KD group reported a decrease in severity of their worst seizure compared to 32% of the CAU group. ConclusionThe KD group resulted in more responders and showed greater improvement on seizure severity. Furthermore, the KD did not lead to worsening of side-effects other than gastro-intestinal problems (only at 4 months’ follow-up). However, as only a minimal difference in QALYs was found between the KD group and the CAU group, the resulting cost per QALY ratios were inconclusive.

Cost-Effectiveness Analysis of Intensity Modulated Radiation Therapy Versus 3-Dimensional Conformal Radiation Therapy for Preoperative Treatment of Extremity Soft Tissue Sarcomas

Create a cost-effectiveness model comparing preoperative intensity modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3DCRT) for extremity soft tissue sarcomas. Input parameters included 5-year local recurrence rates, rates of acute wound adverse events, and chronic toxicities (edema, fracture, joint stiffness, and fibrosis). Health-state utilities were used to calculate quality-adjusted life years (QALYs). Overall treatment costs per QALY or incremental cost-effectiveness ratio (ICER) were calculated. Roll-back analysis was performed using average costs and utilities to determine the baseline preferred radiation technique. One-way, 2-way, and probabilistic sensitivity analyses (PSA) were performed for input parameters with the largest impact on the ICER. Overall treatment costs were $17,515.58 for 3DCRT compared with $22,920.51 for IMRT. The effectiveness was higher for IMRT (3.68 QALYs) thanfor 3DCRT (3.35 QALYs). The baseline ICER for IMRT was $16,842.75/QALY, making it the preferable treatment. The ICER was most sensitive to the probability of local recurrence, upfront radiation costs, local recurrence costs, certain utilities (no toxicity/no recurrence, grade 1 toxicity/no local recurrence, grade 4 toxicity/no local recurrence), and life expectancy. Dominance patterns emerged when the cost of 3DCRT exceeded $15,532.05 (IMRT dominates) or the life expectancy was under 1.68years (3DCRT dominates). Furthermore, preference patterns changed based on the rate of local recurrence (threshold: 13%). The PSA results demonstrated that IMRT was the preferred cost-effective technique for 64% of trials compared with 36% for 3DCRT. Based on our model, IMRT is the preferred technique by lowering rates of local recurrence, severe toxicities, and improving QALYs. From a third-party payer perspective, IMRT should be a supported approach for extremity soft tissue sarcomas.

An economic evaluation of the ketogenic diet versus care as usual in children and adolescents with intractable epilepsy: An interim analysis.

To gain insight into the cost-effectiveness of the ketogenic (KD) diet compared with care as usual (CAU) in children and adolescents with intractable epilepsy, we conducted an economic evaluation from a societal perspective, alongside a randomized controlled trial. Participants from a tertiary epilepsy center were randomized into KD (intervention) group or CAU (control) group. Seizure frequency, quality adjusted life years (QALYs), health care costs, production losses of parents and patient, and family costs were assessed at baseline and during a 4-month study period and compared between the intervention and control groups. The incremental cost-effectiveness ratios (ICERs) (i.e., cost per QALY and cost per responder), and cost-effectiveness acceptability curves (CEACs) were calculated and presented. In total, 48 children were included in the analyses of this study (26 KD group). At 4 months, 50% of the participants in the KD group had a seizure reduction ≥50% from baseline, compared with 18.2 of the participants in the CAU group. The mean costs per patient in the CAU group were €15,245 compared to €20,986 per patient in the KD group, resulting in an ICER of €18,044 per responder. We failed, however, to measure any benefits in terms of QALYs and therefore, the cost per QALY rise high above any acceptable ceiling ratio. It might be that the quality of life instruments used in this study were not sufficiently sensitive to detect changes, or it might be that being a clinical responder is not sufficient to improve a patient's quality of life. Univariate and multivariate sensitivity analyses and nonparametric bootstrapping were performed and demonstrated the robustness of our results. The results show that the KD reduces seizure frequency. The study did not find any improvements in quality of life and, therefore, unfavorable cost per QALY ratio's resulted.

IMPLICATIONS OF GLOBAL PRICING POLICIES ON ACCESS TO INNOVATIVE DRUGS: THE CASE OF TRASTUZUMAB IN SEVEN LATIN AMERICAN COUNTRIES.

Differential pricing, based on countries' purchasing power, is recommended by the World Health Organization to secure affordable medicines. However, in developing countries innovative drugs often have similar or even higher prices than in high-income countries. We evaluated the potential implications of trastuzumab global pricing policies in terms of cost-effectiveness (CE), coverage, and accessibility for patients with breast cancer in Latin America (LA). A Markov model was designed to estimate life-years (LYs), quality-adjusted life-years (QALYs), and costs from a healthcare perspective. To better fit local cancer prognosis, a base case scenario using transition probabilities from clinical trials was complemented with two alternative scenarios with transition probabilities adjusted to reflect breast cancer epidemiology in each country. Incremental discounted benefits ranged from 0.87 to 1.00 LY and 0.51 to 0.60 QALY and incremental CE ratios from USD 42,104 to USD 110,283 per QALY (2012 U.S. dollars), equivalent to 3.6 gross domestic product per capita (GDPPC) per QALY in Uruguay and to 35.5 GDPPC in Bolivia. Probabilistic sensitivity analysis showed 0 percent probability that trastuzumab is CE if the willingness-to-pay threshold is one GDPPC per QALY, and remained so at three GDPPC threshold except for Chile and Uruguay (4.3 percent and 26.6 percent, respectively). Trastuzumab price would need to decrease between 69.6 percent to 94.9 percent to became CE in LA. Although CE in other settings, trastuzumab was not CE in LA. The use of health technology assessment to prioritize resource allocation and support price negotiations is critical to making innovative drugs available and affordable in developing countries.

Willingness to pay for a quality-adjusted life year: an evaluation of attitudes towards risk and preferences.

BackgroundThis paper examines the Willingness to Pay (WTP) for a quality-adjusted life year (QALY) expressed by people who attended the healthcare system as well as the association of attitude towards risk and other personal characteristics with their response.MethodsHealth-state preferences, measured by EuroQol (EQ-5D-3L), were combined with WTP for recovering a perfect health state. WTP was assessed using close-ended, iterative bidding, contingent valuation method. Data on demographic and socioeconomic characteristics, as well as usage of health services by the subjects were collected. The attitude towards risk was evaluated by collecting risky behaviors data, by the subject’s self-evaluation, and through lottery games.ResultsSix hundred and sixty two subjects participated and 449 stated a utility inferior to 1. WTP/QALY ratios varied significantly when payments with personal money (mean €10,119; median €673) or through taxes (mean €28,187; median €915) were suggested. Family income, area income, higher education level, greater use of healthcare services, and the number of co-inhabitants were associated with greater WTP/QALY ratios. Age and female gender were associated with lower WTP/QALY ratios. Risk inclination was independently associated with a greater WTP/QALY when “out of pocket” payments were suggested. Clear discrepancies were demonstrated between linearity and neutrality towards risk assumptions and experimental results.ConclusionsWTP/QALY ratios vary noticeably based on demographic and socioeconomic characteristics of the subject, but also on their attitude towards risk. Knowing the expression of preferences by patients from this outcome measurement can be of interest for health service planning.

Cost-effectiveness of endoscopic surveillance of non-dysplastic Barrett's esophagus

Endoscopic surveillance for non-dysplastic Barrett's esophagus (BE) is contentious and its cost effectiveness unclear. To perform an economic analysis of endoscopic surveillance strategies. Cost-utility analysis by using a simulation Markov model to synthesize evidence from large epidemiologic studies and clinical data for surveillance, based on international guidelines, applied in a coordinator-managed surveillance program. Tertiary care hospital, South Australia. A total of 2040 patient-years of follow-up. (1) No surveillance, (2) 2-yearly endoscopic surveillance of patients with non-dysplastic BE and 6-monthly surveillance of patients with low-grade dysplasia, (3) a hypothetical strategy of biomarker-modified surveillance. U.S. cost per quality-adjusted life year (QALY) ratios. Compared with no surveillance, surveillance produced an estimated incremental cost per QALY ratio of $60,858. This was reduced to $38,307 when surveillance practice was modified by a hypothetical biomarker-based strategy. Sensitivity analyses indicated that the likelihood that surveillance alone was cost-effective compared with no surveillance was 16.0% and 60.6% if a hypothetical biomarker-based strategy was added to surveillance, at an acceptability threshold of $100,000 per QALY gained. Treatment options for BE that overlap those for symptomatic GERD were omitted. By using best available estimates of the malignant potential of BE, endoscopic surveillance of patients with non-dysplastic BE is unlikely to be cost-effective for the majority of patients and depends heavily on progression rates between dysplasia grades. However, strategies that modify surveillance according to cancer risk might be cost-effective, provided that high-risk individuals can be identified and prioritized for surveillance.

A modeled economic evaluation of sevelamer for treatment of hyperphosphatemia associated with chronic kidney disease among patients on dialysis in the United Kingdom

Objective:There is limited information regarding the cost-effectiveness of sevelamer for the treatment of hyperphosphatemia in chronic kidney disease (CKD) patients on dialysis in the UK. Using a UK National Health Service (NHS) perspective and final results of the Dialysis Clinical Outcomes Revisited (DCOR) study, an evaluation was performed to determine the cost-effectiveness of sevelamer compared to calcium-based phosphate binders for the first-line treatment of hyperphosphatemia in CKD patients on dialysis.Methods:A Markov model was developed to estimate life years, quality-adjusted life years (QALYs), costs, incremental cost per life year (LY) gained, and QALY gained. Treatment-specific overall survival up to 44 months, hospitalizations, and resource utilization were derived from the DCOR study. Survival was extrapolated to a lifetime horizon using Weibull regression analysis. Unit costs and utility estimates specific to the UK were obtained from the published literature. Sub-group analyses were conducted based on data reported from the DCOR study for increasing age cut-points. Outcomes and costs were modeled for a lifetime horizon.Results:In the base case analysis, the use of sevelamer resulted in a gain of ∼0.73 LYs and 0.44 QALYs per patient (discounted at 3.5% per year). Total per-patient costs were higher for sevelamer, resulting in an incremental cost of £22,157 per QALY gained and £13,427 per LY gained (in £2009). Increasingly favorable cost per QALY ratios were observed with increasing age cut-points, ranging from £15,864 for patients ≥45 to £13,296 for patients ≥65 years of age. Results were most sensitive to assumptions regarding overall survival and the inclusion of dialysis costs. Key limitations of the analysis included the use of non-UK trial data for survival and hospitalizations, and the exclusion of quality-of-life impacts associated with hospitalization.Conclusions:In CKD patients receiving dialysis, treatment of hyperphosphatemia with sevelamer offers good value for money compared with calcium-based binders.

Cost-Effectiveness of Double-Unit Cord Blood Transplantation Versus Single-Unit Cord Blood Transplantation in Adult Patients with Acute Leukaemia in France- On Behalf of SFGM-TC, Eurocord, ALWP-EBMT

Abstract 3130Unrelated donor cord blood transplantation (UCBT) using a single (s) or double (d) CB unit has become a widely accepted treatment for hematologic diseases in the absence of an HLA identical stem cell donor. Retrospective studies have reported a reduced risk of relapse after dUCBT compared with sUCBT, however one limitation of using dUCBT is the cost of the 2 units, but comparison of the total cost of the 2 procedures has not yet been published.The aim of this study was to evaluate the outcome of adult patients transplanted for acute leukaemia in first remission and to access the cost-effectiveness of dUCBT compared to sUCBT). We analyzed clinical results and costs of 134 consecutive CBT performed in 31 transplant centers in France from 2001 to 2009.All hospital costs were estimated from donor search to 1 year after UCBT, according to the French public system. A Markov decision analysis model was used to calculate the QALY (quality-adjusted life years) and cost-effectiveness ratio (ICER). For cost-effectiveness analysis, reduced intensity conditioning (RIC) and myeloablative conditioning (MAC) were studied separately.Forty patients were transplanted for ALL and 94 for AML in CR1. Median age was 42 years and median time from diagnosis to UCBT was 180 days. CMV serology for 49% of patients was negative. Sixty one patients received a sUCBT and 73 a dUCBT. Twenty eight percent of CB units were HLA identical to recipient or had 1 HLA disparity (antigen level for HLA-A and B allelic level for DRB1) and 72% had 2–3 HLA disparities. Median infused nucleated cell dose was 2.7×107/kg in sUCBT and 3.8×107/kg in dUCBT.Seventy nine patients received a RIC (97% TBI<4Gy based) and 55 a MAC (84% TBI ≥4Gy Based). The median follow-up was 31 months after sUCBT and 24 months after dUCBT. Neutrophil recovery was achieved in 115 patients (51 of 61 patients who received a sUCBT and 64 of 73 dUCBT), with a median time of 23 (6–53) days. No statistical difference was observed for neutrophil recovery after sUCBT or dUCBT. dUCBT was associated with a higher rate of acute GVHD grade II-IV: 56% versus 30% for sUCBT, p=0.003.At day +100, 53% of patients experienced CMV reactivation (37% after sUCBT and 71% after dUCBT, p=0.01), 45% had viral infection other than CMV and 49% had bacterial infection.Fifteen patients (11%) received a second transplant, 6 for graft failure (4 in sUCBT group and 2 in dUCBT group) and 9 for relapse (6 in sUCBT group and 3 in dUCBT group). The median interval between first and second transplant was 327 days.The estimated survival at 2 years was 40±6% vs 58±6% after sUCBT and dUCBT, respectively (p=0.04). Leukaemia-free survival at 2 years was 30±6% in sUCBT vs 49±6% in dUCBT, (p=0.09). Cumulative incidence of relapse at 2 years was lower after dUCBT: 29±4% vs to 42±4% after sUCBT, (p=0.04). No statistically significant difference was observed in terms of non-relapse mortality and incidence of chronic GVHD.The mean cost for donor identification and UCB acquisition was 28.164 € for sUCBT and 48.929 € for dUCBT. The estimated costs within 1 year after RIC-sUCBT was 133.790 € and it was 211.735 € after MAC-sUCBT. The estimated cost was 180.549 € after RIC-dUCBT and 205.375 €, after MAC-dUCBT. Table 1 summarizes details of costs by type of graft and conditioning. In the MAC group, dUCBT was associated with lower cost (minus 13.554€) and better effectiveness (plus 0, 53 QALY). The cost per QALY obtained after RIC-dUCBT compared with sUCBT was 91.199 €. In conclusion, In France, dUCBT is associated with higher incidence of acute GVHD, lower relapse and better survival in adults transplanted for acute leukaemia. With a MAC, dUCBT is the best option, and the cost per QALY obtained for dUCBT when using RIC is acceptable.TableEstimated costs from donor search to 1 year after transplantation for single UCBT, double UCBT and type of conditioning regimen (MAC or RIC)sUCBTdUCBTCB unit search28 164 €48 929 €MACInitial hospitalisationMean duration (d)6665Mean cost137.757 €131.773 €Outpatient visitsNumber of days911Mean cost7.788 €9.223 €Further hospitalisationsMean duration (d)5023Mean cost38.026 €15.449 €Total mean cost within 1 year211.735 €205.374 €RICInitial hospitalisationMean duration (d)2948Mean cost58.621 €96.335 €Outpatient visitsNumber of days2123Mean cost17.870 €19.366 €Further hospitalisationsMean duration (d)4021Mean cost29.135 €15.918 €Total mean cost within 1 year133.790 €180.549 € Disclosures:No relevant conflicts of interest to declare.