Cost-effectiveness analysis of FOLFIRINOX vs gemcitabine with nab-paclitaxel as adjuvant treatment for resected pancreatic cancer in the United States based on PRODIGE-24 and APACT trials.

BACKGROUND: Pancreatic cancer is associated with low median overall survival. Combination chemotherapy regimens FOLFIRINOX and gemcitabine with nab-paclitaxel (GemNab) are the new adjuvant treatment standards for resectable pancreatic cancer. PRODIGE-24 and APACT trials demonstrated superior clinical outcomes with FOLFIRINOX and GemNab, each vs gemcitabine monotherapy. OBJECTIVE: To evaluate the cost-effectiveness of FOLFIRINOX vs GemNab for resectable pancreatic cancer in adults from the U.S. payer perspective, in order to inform decision makers about which of these treatments is optimal. METHODS: A Markov model with 3 disease states (relapse free, progressive disease, and death) was developed. Cycle length was 1 month, and time horizon was 10 years. Transition probabilities were derived from PRODIGE-24 and APACT survival data. All cost and utility input parameters were obtained from published literature. Cost-effectiveness analysis was performed to obtain total costs, quality-adjusted life-years (QALYs), life-years (LYs), and incremental cost-effectiveness ratio (ICER). A 3% annual discount rate was applied to costs and outcomes. The effect of uncertainty on model parameters was assessed with 1-way and probabilistic sensitivity analysis (PSA). RESULTS: Our analysis estimated that the cost for FOLFIRINOX was $40,831 higher than GemNab ($99,669 vs. $58,837). Despite increased toxicity, FOLFIRINOX was associated with additional 0.18 QALYs and 0.25 LYs compared with GemNab (QALY: 1.65 vs. 1.47; LY: 2.09 vs. 1.84). The ICER for FOLFIRINOX vs GemNab was $226,841 per QALY and $163,325 per LY. FOLFIRINOX was not cost-effective at a willingness-to-pay (WTP) threshold of $200,000 per QALY, and this was confirmed by the PSA. CONCLUSIONS: Total monthly cost for FOLFIRINOX was approximately 1.7 times higher than GemNab. If the WTP threshold increases to or above $250,000 per QALY, FOLFIRINOX then becomes a cost-effective treatment option. DISCLOSURES: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors have no conflicts of interest to declare.

Estimating the Theoretical Cost Implications of Funding New Drugs Considered Not to Be Cost-Effective.

This study aims to estimate the theoretical excess expenditure that would be incurred by the Irish state-payer, should drugs be reimbursed at their original asking ("list") price rather than at a price at which the drug is considered cost-effective. In Ireland, all new drugs are evaluated by the National Centre for Pharmacoeconomics. For this study, drugs that were submitted by pharmaceutical companies from 2012 to 2017 and considered not cost-effective at list price were reviewed. A total of 43 such drugs met our inclusion criteria, and their pharmacoeconomic evaluations were further assessed. The price at which the drug could be considered cost-effective (cost-effective price) at the upper cost-effectiveness threshold used in Ireland (€ 45 000/quality adjusted life-year) was estimated for 18 drugs with an available cost-effectiveness model. Then, for each drug, the list price and cost-effective price (both per unit) were both individually applied to 1 year of national real-world drug utilization data. This allowed the estimation of the expected expenditures under the assumptions of list price paid and cost-effective price paid. The resulting theoretical excess expenditure, the expenditure at list price minus the expenditure at the cost-effective price, was estimated to be €108.2 million. This estimate is theoretical because of the confidentiality of actual drug prices. The estimation is calculated using the list price and likely overestimates the actual excess expenditure, which would reduce to zero if cost-effective prices are agreed. Nevertheless, this estimate illustrates the importance of a process to assess the value of new drugs so that potential excess drug expenditure is identified.

A randomized controlled trial of the X-Stop interspinous distractor device versus laminectomy for lumbar spinal stenosis with 2-year quality-of-life and cost-effectiveness outcomes.

OBJECTIVE: Lumbar spinal stenosis (LSS) is a common and debilitating condition that is increasing in prevalence in the world population. Surgical decompression is often standard treatment when conservative measures have failed. Interspinous distractor devices (IDDs) have been proposed as a safe alternative; however, the associated cost and early reports of high failure rates have brought their use into question. The primary objective of this study was to determine the cost-effectiveness and long-term quality-of-life (QOL) outcomes after treatment of LSS with the X-Stop IDD compared with surgical decompression by laminectomy. METHODS: A multicenter, open-label randomized controlled trial of 47 patients with LSS was conducted; 21 patients underwent insertion of the X-Stop device and 26 underwent laminectomy. The primary outcomes were monetary cost and QOL measured using the EQ-5D questionnaire administered at 6-, 12-, and 24-month time points. RESULTS: The mean monetary cost for the laminectomy group was £2712 ($3316 [USD]), and the mean cost for the X-Stop group was £5148 ($6295): £1799 ($2199) procedural cost plus £3349 mean device cost (£2605 additional cost per device). Using an intention-to-treat analysis, the authors found that the mean quality-adjusted life-year (QALY) gain for the laminectomy group was 0.92 and that for the X-Stop group was 0.81. The incremental cost-effectiveness ratio was -£22,145 (-$27,078). The revision rate for the X-Stop group was 19%. Five patients crossed over to the laminectomy arm after being in the X-Stop group. CONCLUSIONS: Laminectomy was more cost-effective than the X-Stop for the treatment of LSS, primarily due to device cost. The X-Stop device led to an improvement in QOL, but it was less than that in the laminectomy group. The use of the X-Stop IDD should be reserved for cases in which a less-invasive procedure is required. There is no justification for its regular use as an alternative to decompressive surgery. Clinical trial registration no.: ISRCTN88702314 (www.isrctn.com).

Review of economic analysis of available interventions on idiopathic short stature: A protocol for systematic review and meta-analysis.

BACKGROUND: Idiopathic short stature (ISS) causes a high economic burden worldwide. As part of a research project that synthesizes economic evidence for Korean medicine treatment of ISS, we describe the methods that will be used for the comprehensive review of articles that analyze health-related economic evaluation for available interventions for ISS using a systematic review methodology. METHODS: Eight electronic English, Korean, and Chinese databases will be searched from their inception until December 2020 to identify studies on the economic evaluation of available interventions on ISS, without language, study design, or publication status restrictions. From the included studies, the effectiveness, utility, and cost data will be collected as the outcome measures by two researchers independently. Descriptive analysis of individual studies will be conducted. If it is judged that the interventions and outcomes of the included studies are sufficiently homogeneous, we will attempt a quantitative synthesis through meta-analysis using Review Manager version 5.4 software (Cochrane, London, UK). RESULTS: This study will summarize the evidence regarding the economic evaluation of available interventions for ISS. CONCLUSIONS: The findings of this review will help clinicians and patients in evidence-based decision-making in clinical settings and help policy makers develop effective policies and distribute resources based on the available evidence.

Cost-effectiveness of photobiomodulation therapy for the prevention and management of cancer treatment toxicities: a systematic review.

PURPOSE: To identify and summarize the evidence on the cost-effectiveness of photobiomodulation (PBM) therapy for the prevention and treatment of cancer treatment-related toxicities. METHODS: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) and Meta-analysis Of Observational Studies in Epidemiology (MOOSE). Scopus, MEDLINE/PubMed, and Embase were searched electronically. RESULTS: A total of 1490 studies were identified, and after a two-step review, 4 articles met the inclusion criteria. The included studies analyzed the cost-effectiveness of PBM therapy used in the context of lymphedema for breast cancer and oral mucositis (OM) induced by chemotherapy and radiotherapy. Better outcomes were associated with PBM therapy. The incremental cost-effectiveness ratio ranged from 3050.75 USD to 5592.10 USD per grade 3-4 OM case prevented. PBM therapy cost 21.47 USD per percentage point reduction in lymphedema in comparison with 80.51 USD for manual lymph drainage and physical therapy. CONCLUSION: There is limited evidence that PBM therapy is cost-effective in the prevention and treatment of specific cancer treatment-related toxicities, namely, OM and breast cancer-related lymphedema. Studies may have underreported the benefits due to a lack of a comprehensive cost evaluation. This suggests a wider acceptance of PBM therapy at cancer treatment centers, which has thus far been limited by the number of robust clinical studies that demonstrate cost-effectiveness for the prevention and treatment of toxicities.

Cost-effectiveness randomized clinical trial on the effect of photobiomodulation therapy for prevention of radiotherapy-induced severe oral mucositis in a Brazilian cancer hospital setting.

OBJECTIVES: This study aimed to assess the cost-effectiveness of photobiomodulation therapy (PBMT) in association with a Preventive Oral Care Program (POCP) compared with POCP alone in the treatment of radiotherapy (RT)-induced oral mucositis (OM). METHODS: The cost-effectiveness was evaluated from the health provider perspective and conducted alongside a randomized, double-blind clinical trial. Participants were randomly assigned to either PBMT (n = 25) or control (n = 23) group. The PBMT group participants received PBMT associated with POCP. In the control group, patients were submitted to POCP alone. Costs were identified, quantified, and valued through observation and consultation of the hospital's financial sector database and estimated in Brazilian real and converted to international dollars using the purchasing power parity exchange rate. The incremental cost-effectiveness ratio (ICER) was estimated by considering the prevention of severe OM, interruption of RT, and oral health-related quality of life (OHRQoL) scores, measured by the OHIP-14 and patient-reported OM symptoms scale (PROMS). RESULTS: The incremental cost of PBMT was $857.35, and the cost per session was $25.69. The ICER was $ 2867.39 to avoid one case of severe OM and $ 2756.75 to prevent one interruption in RT due to OM. ICER to reduce 1 point in OHIP-14 and PROMS scores were $170.79 and $31.75, respectively. CONCLUSION: PBMT is more cost-effective than POCP alone in preventing severe OM, worsening of the OHRQoL, and RT interruptions. PBMT is a promising therapy, especially to avoid interruptions in oncological treatment. TRIAL REGISTRATION: ReBEC-RBR-5h4y4n.

An Initial Cost-Effectiveness Analysis of Magnetic Resonance-Guided Laser Interstitial Thermal Therapy in Pediatric Epilepsy Surgery.

INTRODUCTION: Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a new technology that provides a clinically efficacious and minimally invasive alternative to conventional microsurgical resection. However, little data exist on how costs compare to traditional open surgery. The goal of this paper is to investigate the cost-effectiveness of MRgLITT in the treatment of pediatric epilepsy. METHODS: We retrospectively analyzed the medical records of pediatric patients who underwent MRgLITT via the Visualase® thermal therapy system (Medtronic, Inc., Minneapolis, MN, USA) between December 2013 and September 2017. Direct costs associated with preoperative, operative, and follow-up care were extracted. Benefit was calculated in quality-adjusted life years (QALYs), and the cost-effectiveness was derived from the discounted total direct costs over QALY. Sensitivity analysis on 4 variables was utilized to assess the validity of our results. RESULTS: Twelve consecutive pediatric patients with medically refractory epilepsy underwent MRgLITT procedures. At the last postoperative follow-up, 8 patients were seizure free (Engel I, 66.7%), 2 demonstrated significant improvement (Engel II, 16.7%), and 2 patients showed worthwhile improvement (Engel III, 16.7%). The average cumulative discounted QALY was 2.11 over the lifetime of a patient. Adjusting for inflation, MRgLITT procedures had a cost-effectiveness of USD 22,211 per QALY. Our sensitivity analysis of cost variables is robust and supports the procedure to be cost--effective. CONCLUSION: Our data suggests that MRgLITT may be a cost-effective alternative to traditional surgical resection in pediatric epilepsy surgery.

Lenvatinib versus sorafenib for unresectable hepatocellular carcinoma: a cost-effectiveness analysis.

Aim: To investigate the cost-effectiveness of lenvatinib and sorafenib in the treatment of patients with nonresected hepatocellular carcinoma in China. Materials & methods: Markov model was used to simulate the direct medical cost and quality-adjusted life years (QALY) of patients with hepatocellular carcinoma. Clinical data were derived from the Phase 3 randomized clinical trial in a Chinese population. Results: Sorafenib treatment resulted in 1.794 QALYs at a cost of $43,780.73. Lenvatinib treatment resulted in 2.916 QALYs for patients weighing <60 and ≥60 kg at a cost of $57,049.43 and $75,900.36, The incremental cost-effectiveness ratio to the sorafenib treatment group was $11,825.94/QALY and $28,627.12/QALY, respectively. Conclusion: According to WHO's triple GDP per capita, the use of lenvatinib by providing drugs is a cost-effective strategy.

A Cost-Effectiveness Analysis Comparing Single-use and Traditional Negative Pressure Wound Therapy to Treat Chronic Venous and Diabetic Foot Ulcers.

Lower extremity ulcers such as venous leg ulcers (VLUs) and diabetic foot ulcers (DFUs) have a major clinical and economic impact on patients and providers. PURPOSE: The purpose of this economic evaluation was to determine the cost-effectiveness of single-use negative pressure wound therapy (sNPWT) compared with traditional NPWT (tNPWT) for the treatment of VLUs and DFUs in the United States. METHODS: A Markov decision-analytic model was used to compare the incremental cost and ulcer weeks avoided for a time horizon of 12 and 26 weeks using lower extremity ulcer closure rates from a published randomized controlled trial (N = 161) that compared sNPWT with tNPWT. Treatment costs were extracted from a retrospective cost-minimization study of sNPWT and tNPWT from the payer perspective using US national 2016 Medicare claims data inflated to 2018 costs and multiplied by 7 to estimate the weekly costs of treatment for sNPWT and tNPWT. Two (2) arms of the model, tNPWT and sNPWT, were calculated separately for a combination of both VLU and DFU ulcer types. In this model, a hypothetical cohort of patients began in the open ulcer health state, and at the end of each weekly cycle a proportion of the cohort moved into the closed ulcer health state according to a constant transition probability. The costs over the defined timescale were summed to give a total cost of treatment for each arm of the model, and then the difference between the arms was calculated. Effectiveness was calculated by noting the incidence of healing at 12 and 26 weeks and the total number of open ulcer weeks; the incremental effectiveness was calculated as sNPWT effectiveness minus tNPWT effectiveness. Data were extracted to Excel spreadsheets and subjected to one-way sensitivity, scenario (where patients with unhealed ulcers were changed to standard care at 4 or 12 weeks), probabilistic, and threshold analyses. RESULTS: sNPWT was found to provide an expected cost saving of $7756 per patient and an expected reduction of 1.67 open ulcer weeks per patient over 12 weeks and a cost reduction of $15 749 and 5.31 open ulcer weeks over 26 weeks. Probabilistic analysis at 26 weeks showed 99.8% of the simulations resulted in sNPWT dominating tNPWT. Scenario analyses showed that sNPWT remained dominant over tNPWT (cost reductions over 26 weeks of $2536 and $7976 per patient, respectively). CONCLUSION: Using sNPWT for VLUs and DFUs is likely to be more cost-effective than tNPWT from the US payer perspective and may provide an opportunity for policymakers to reduce the economic burden of lower extremity ulcers.

Modelling cost benefit of community-oriented primary care in rural South Africa.

BACKGROUND: Globally, rural populations have poorer health and considerably lower levels of access to healthcare compared with urban populations. Although the drive to ensure universal coverage through community healthcare worker programmes has shown significant results elsewhere, their value has yet to be realised in South Africa. AIM: The aim of this study was to determine the potential impact, cost-effectiveness and benefit-to-cost ratio (BCR) of information and communications technology (ICT)-enabled community-oriented primary care (COPC) for rural and remote populations. SETTING: The Waterberg district of Limpopo province in South Africa is a rural mining area. The majority of 745 000 population are poor and in poor health. METHODS: The modelling considers condition-specific effectiveness, population age and characteristics, health-determined service demand, and costs of delivery and resources. RESULTS: Modelling showed 122 teams can deliver a full ICT-enabled COPC service package to 630 565 eligible people. Annually, at scale, it could yield 35 877 unadjusted life years saved and 994 deaths avoided at an average per capita service cost of R170.37, and R2668 per life year saved. There could be net annual savings of R120 million (R63.4m for Waterberg district) from reduced clinic (110.7m) and hospital outpatient (23 646) attendance and admissions. The service would inject R51.6m into community health worker (CHW) households and approximately R492m into district poverty reduction and economic growth. CONCLUSION: With a BCR of 3.4, ICT-enabled COPC is an affordable systemic investment in universal, pro-poor, integrated healthcare and makes community-based healthcare delivery particularly compelling in rural and remote areas.

Impact of stakeholder perspectives on cost-effectiveness estimates of four specialized nutritious foods for preventing stunting and wasting in children 6-23 months in Burkina Faso.

BACKGROUND: Multiple specialized nutritious food options are programmed for supplementation in humanitarian and development settings. However, comparative cost-effectiveness evidence is lacking, let alone incorporation of perspectives from uncompensated stakeholders. A Burkina Faso trial evaluated the cost-effectiveness of Corn Soy Blend Plus w/ oil (CSB+ w/oil, reference arm), Corn Soy Whey Blend w/oil (CSWB w/oil), Super Cereal Plus (SC+), and Ready-to-Use Supplementary Food (RUSF) in reducing stunting and wasting among children 6-23 months old. This paper presents cost-effectiveness findings from multiple stakeholders' perspectives, including caregivers and program volunteers. METHODS: An activity-based costing with ingredients approach was used to summarize cost of the 18-month-long blanket supplementary feeding for each enrolled child (in 2018 USD). Time data were collected using self-reported and observational instruments. Cost-effectiveness relative to CSB+ w/oil assessed incremental cost per enrolled child against incremental outcomes: prevalence of stunting at 23 months of age and number of months of wasting. Two combined perspectives were compared: program (donor, implementer, and volunteer) versus program and caregiver (adding caregiver). RESULTS: A total of 6112 children were enrolled. While similar effectiveness was found in three arms (CSWB w/oil was less effective), costs differed. Product cost and caregiver time to prepare study foods were major drivers of cross-arm cost differences from the respective combined perspective. The two major drivers were used to construct uncertainty ranges of cost per enrolled child from program and caregiver perspective: $317 ($279- $355) in CSB+ w/oil, $350 ($327- $373) in CSWB w/oil, $387 ($371- $403) in RUSF, and $434 ($365- $503) in SC+. Cost from program and caregiver perspective was a substantial increase from program perspective. CSB+ w/oil was most cost-effective in reducing stunting and wasting, and this main finding was robust to changing perspectives and all corresponding sensitivity analyses when uncompensated time was valued at minimum wage ($0.36/h). The break-even point for uncompensated time valuation is >$0.84/h, where RUSF became the most cost-effective from the program and caregiver perspective. Relative cost-effectiveness rankings among the other three arms depended on choice of perspectives, and were sensitive to values assigned to product cost, international freight cost, opportunity cost of time, and outcomes of a hypothetical control. Volunteer opportunity cost did not affect arm comparisons, but lack of compensation resulted in negative financial consequences for caregivers. CONCLUSIONS: Evaluating cost-effectiveness by incorporating uncompensated stakeholders provided crucial implementation insights around nutrition products and programming. TRIAL REGISTRATION: Trial registration number: NCT02071563. Name of registry: ClinicalTrials.gov URL of registry: https://clinicaltrials.gov/ct2/show/NCT02071563?type=Intr&cond=Malnutrition&cntry=BF&draw=2&rank=9 Date of registration: February 26, 2014. Date of enrollment of first participant: July 2014.

Assessing the value for money of an integrated health and wellbeing service in the UK.

Lay health workers have been utilized to deliver health promotion programmes in a variety of settings. However, few studies have sought to determine whether these programmes represent value for money, particularly in a UK context. The present study involved an economic evaluation of Wellbeing for Life, an integrated health and wellbeing service in northern England. The service combined one-to-one interventions delivered by lay health workers (known as health trainers), group wellbeing interventions, volunteering opportunities and other community development activities. Value for money was assessed using an established economic model developed with input from a panel of commissioners and providers, and the main data source was the national health trainer data collection and reporting system. Between June 2015 and January 2017, behaviour change outcomes (i.e. whether client goals in relation to diet, physical activity, smoking or other behaviours, had been achieved) were recorded for 2433 of the 3179 individuals who accessed one-to-one interventions. The level of achievement observed gave an estimated total health gain of 287.7 quality-adjusted life years (QALYs). In addition, there were 4669 health-promoting events, five asset mapping projects and 1595 occurrences of signposting to other services. Combining the value of individual behaviour change with the value of these additional activities gave an overall net cost per QALY gained of £3900 and a total estimated societal value of at least £3.45 for every £1 spent on the service. These results suggest that the Wellbeing for Life service offered good value for money. Further research is needed to systematically and comprehensively determine the societal value of similar holistic, asset-based and lay-led approaches.

Cost-effectiveness of an exercise and nutritional intervention versus usual nutritional care during adjuvant treatment for localized breast cancer: the PASAPAS randomized controlled trial.

We undertook a cost-effectiveness analysis (CEA) to compare an exercise and nutritional program with the usual nutritional care concomitant to adjuvant chemotherapy in localized breast cancer patients. The CEA was designed as part of the interventional, controlled, randomized, single-center, open-label PASAPAS study. Breast cancer patients receiving first-line adjuvant chemotherapy at a French Comprehensive Cancer Center were randomized 2:1 to a 6-month exercise program of supervised indoor and outdoor group sessions in addition to usual nutritional care (exercise arm) or a usual nutritional care group receiving dietary and physical activity counseling (control arm). Costs were assessed from the French national insurance perspective (in Euros, 2012). Incremental cost-effectiveness ratios (ICERs) were calculated for four criteria: body mass index, waist circumference, body fat percentage, and estimated aerobic capacity. Uncertainty around the ICERs was captured by a probabilistic analysis using a non-parametric bootstrap method. The analysis was based on 60 patients enrolled between 2011 and 2013. Average intervention costs per participant were €412 in the exercise arm (n = 41) and €117 (n = 19) in the control arm. Total mean costs were €17,344 (standard deviation 9,928) and €20,615 (standard deviation 14,904), respectively, did not differ significantly (p = 0.51). The 6-month exercise program was deemed to be cost-effective compared with usual care for the estimated aerobic capacity. Multicenter randomized studies with long-term costs and outcomes should be done to provide additional evidence. Clinical trial: The PASAPAS study is registered under ClinicalTrials.gov. Trial registration ID: NCT01331772.

Clinical outcome and cost-effectiveness of a 1-year nutritional intervention programme in COPD patients with low muscle mass: The randomized controlled NUTRAIN trial.

BACKGROUND AND AIMS: The efficacy of nutritional intervention to enhance short- and long-term outcomes of pulmonary rehabilitation in COPD is still unclear, hence this paper aims to investigate the clinical outcome and cost-effectiveness of a 12-month nutritional intervention strategy in muscle-wasted COPD patients. METHODS: Prior to a 4-month pulmonary rehabilitation programme, 81 muscle-wasted COPD patients (51% males, aged 62.5 ± 0.9 years) with moderate airflow obstruction (FEV1 55.1 ± 2.2% predicted) and impaired exercise capacity (Wmax 63.5 ± 2.4% predicted) were randomized to 3 portions of nutritional supplementation per day (enriched with leucine, vitamin D and polyunsaturated fatty acids) [NUTRITION] or PLACEBO (phase 1). In the unblinded 8-month maintenance phase (phase 2), both groups received structured feedback on their physical activity level assessed by accelerometry. NUTRITION additionally received 1 portion of supplemental nutrition per day and motivational interviewing-based nutritional counselling. A 3-month follow-up (phase 3) was included. RESULTS: After 12 months, physical capacity measured by quadriceps muscle strength and cycle endurance time were not different, but physical activity was higher in NUTRITION than in PLACEBO (Δ1030 steps/day, p = 0.025). Plasma levels of the enriched nutrients (p < 0.001) were higher in NUTRITION than PLACEBO. Trends towards weight gain in NUTRITION and weight loss in PLACEBO led to a significant between-group difference after 12 months (Δ1.54 kg, p = 0.041). The HADS anxiety and depression scores improved in NUTRITION only (Δ-1.92 points, p = 0.037). Generic quality of life (EQ-5D) was decreased in PLACEBO but not in NUTRITION (between-group difference after 15 months 0.072 points, p = 0.009). Overall motivation towards exercising and healthy eating was high and did not change significantly after 12 months; only amotivation towards healthy eating yielded a significant between-group difference (Δ1.022 points, p = 0.015). The cost per quality-adjusted life-year after 15 months was EUR 16,750. CONCLUSIONS: Nutritional intervention in muscle-wasted patients with moderate COPD does not enhance long-term outcome of exercise training on physical capacity but ameliorates plasma levels of the supplemented nutrients, total body weight, physical activity and generic health status, at an acceptable increase of costs for patients with high disease burden.

Clinical- and Cost-Effectiveness of a Mandibular Advancement Device Versus Continuous Positive Airway Pressure in Moderate Obstructive Sleep Apnea.

STUDY OBJECTIVES: Limited evidence exists on the cost-effectiveness of mandibular advancement device (MAD) compared to continuous positive airway pressure (CPAP) therapy in moderate obstructive sleep apnea (OSA). Therefore, this study compares the clinical and cost-effectiveness of MAD therapy with CPAP therapy in moderate OSA. METHODS: In a multicentre randomized controlled trial, patients with an apnea-hypopnea index (AHI) of 15 to 30 events/h were randomized to either MAD or CPAP. Incremental cost-effectiveness and cost-utility ratios (ICER/ICUR, in terms of AHI reduction and quality-adjusted life-years [QALYs, based on the EuroQol Five-Dimension Quality of Life questionnaire]) were calculated after 12 months, all from a societal perspective. RESULTS: In the 85 randomized patients (n = 42 CPAP, n = 43 MAD), AHI reduction was significantly greater with CPAP (median reduction AHI 18.3 [14.8-22.6] events/h) than with MAD therapy (median reduction AHI 13.5 [8.5-18.4] events/h) after 12 months. Societal costs after 12 months were higher for MAD than for CPAP (mean difference €2.156). MAD was less cost-effective than CPAP after 12 months (ICER -€305 [-€3.003 to €1.572] per AHI point improvement). However, in terms of QALY, MAD performed better than CPAP after 12 months (€33.701 [-€191.106 to €562.271] per QALY gained). CONCLUSIONS: CPAP was more clinically effective (in terms of AHI reduction) and cost-effective than MAD. However, costs per QALY was better with MAD as compared to CPAP. Therefore, CPAP is the first-choice treatment option in moderate OSA and MAD may be a good alternative. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Identifier: NCT01588275.

As Value Assessment Frameworks Evolve, Are They Finally Ready for Prime Time?

BACKGROUND: Value assessment frameworks have emerged as tools to assist healthcare decision makers in the United States in assessing the relative value of healthcare services and treatments. As more healthcare decision makers in the United States-including state government agencies, pharmacy benefit managers, employers, and health plans-publicly consider the adoption of value frameworks, it is increasingly important to critically evaluate their ability to accurately measure value and reliably inform decision making. OBJECTIVE: To examine the evolution of the value assessment landscape in the past two years, including new entrants and updated frameworks, and assess if these changes successfully advance the field of value assessment. METHODS: We analyzed the progress of the three currently active value assessment frameworks developed by the Institute for Clinical and Economic Review, the Innovation and Value Initiative, and the National Comprehensive Cancer Network, against six key areas of concern. RESULTS: Value assessment frameworks are moving closer to meeting the challenge of accurately measuring value and reliably informing healthcare decisions. Each of the six concerns has been addressed in some way by at least one framework. CONCLUSIONS: Although value assessments are potential inputs that can be considered for healthcare decision making, none of them should be the sole input for these decisions. Considering the limitations, they should, at most, be only one of many tools in the toolbox.

Cost-effectiveness analysis of ceftazidime/avibactam compared to imipenem as empirical treatment for complicated urinary tract infections.

Ceftazidime/avibactam (CAZ-AVI) is a novel, fixed-dose combination antibiotic that has been approved in Europe and the United States for patients with complicated urinary tract infections (cUTIs) based on results of a Phase III, randomized, comparative study (RECAPTURE study). The present analysis evaluated cost-effectiveness of CAZ-AVI as an empirical treatment for hospitalized patients with cUTIs from the Italian publicly funded healthcare (third-party payer) perspective. A sequential, patient-level simulation model was developed that followed the clinical course of cUTI and generated 5000 pairs of identical patients (CAZ-AVI or imipenem as empirical treatment). The model included additional impact of resistant pathogens; patients who did not respond to empirical treatment were switched to second-line treatment of colistin+high dose carbapenem in both groups. The time horizon of the model was five years, with an annual discount rate of 3% applied to both costs and quality-adjusted life-years (QALYs). The analysis demonstrated that an intervention sequence (CAZ-AVI followed by colistin+high dose carbapenem) compared with a comparator sequence (imipenem followed by colistin+high dose carbapenem) was associated with a net incremental cost of €1015 per patient but provided better health outcomes in terms of clinical cure (97.65% vs. 91.08%; ∆ = 6.57%), shorter hospital stays (10.65 vs. 12.55 days; ∆ = 1.90 days), and QALYs gained per patient (4.190 vs. 4.063; ∆ = 0.126). The incremental cost-effectiveness ratio was €8039/QALY, which is well below the willingness-to-pay threshold of €30 000/QALY in Italy. The results showed that CAZ-AVI is expected to be a cost-effective treatment compared with imipenem for cUTI in Italy.

Treating repetitive suicidal intrusions using eye movements: study protocol for a multicenter randomized clinical trial.

BACKGROUND: Suicide is a major public health problem, and it remains unclear which processes link suicidal ideation and plans to the act of suicide. Growing evidence shows that the majority of suicidal patients diagnosed with major depression or bipolar disorder report repetitive suicide-related images and thoughts (suicidal intrusions). Various studies showed that vividness of negative as well as positive intrusive images may be reduced by dual task (e.g. eye movements) interventions taxing the working memory. We propose that a dual task intervention may also reduce frequency and intensity of suicidal imagery and may be crucial in preventing the transition from suicidal ideation and planning to actual suicidal behaviour. This study aims a) to evaluate the effectiveness of an Eye Movement Dual Task (EMDT) add-on intervention targeting suicidal imagery in depressed patients, b) to explore the role of potential moderators and mediators in explaining the effect of EMDT, and c) to evaluate the cost-effectiveness of EMDT. METHODS: We will conduct a multi-center randomized clinical trial (RCT) evaluating the effects of EMDT in combination with usual care (n = 45) compared to usual care alone (n = 45). Participants will fill in multiple online batteries of self-report questionnaires as well as complete a semi-structured interview (Intrusion Interview), and online computer tasks. The primary outcome is the frequency and intrusiveness of suicidal imagery. Furthermore, the vividness, emotionality, and content of the suicidal intrusions are evaluated; secondary outcomes include: suicidal behaviour and suicidal ideation, severity of depression, psychological symptoms, rumination, and hopelessness. Finally, potential moderators and mediators are assessed. DISCUSSION: If proven effective, EMDT can be added to regular treatment to reduce the frequency and vividness of suicidal imagery. TRIAL REGISTRATION: The study has been registered on October 17th, 2018 at the Netherlands Trial Register, part of the Dutch Cochrane Centre ( NTR7563 ).

Cost-effectiveness of financial incentives for improving diet and health through Medicare and Medicaid: A microsimulation study.

BACKGROUND: Economic incentives through health insurance may promote healthier behaviors. Little is known about health and economic impacts of incentivizing diet, a leading risk factor for diabetes and cardiovascular disease (CVD), through Medicare and Medicaid. METHODS AND FINDINGS: A validated microsimulation model (CVD-PREDICT) estimated CVD and diabetes cases prevented, quality-adjusted life years (QALYs), health-related costs (formal healthcare, informal healthcare, and lost-productivity costs), and incremental cost-effectiveness ratios (ICERs) of two policy scenarios for adults within Medicare and Medicaid, compared to a base case of no new intervention: (1) 30% subsidy on fruits and vegetables ("F&V incentive") and (2) 30% subsidy on broader healthful foods including F&V, whole grains, nuts/seeds, seafood, and plant oils ("healthy food incentive"). Inputs included national demographic and dietary data from the National Health and Nutrition Examination Survey (NHANES) 2009-2014, policy effects and diet-disease effects from meta-analyses, and policy and health-related costs from established sources. Overall, 82 million adults (35-80 years old) were on Medicare and/or Medicaid. The mean (SD) age was 68.1 (11.4) years, 56.2% were female, and 25.5% were non-whites. Health and cost impacts were simulated over the lifetime of current Medicare and Medicaid participants (average simulated years = 18.3 years). The F&V incentive was estimated to prevent 1.93 million CVD events, gain 4.64 million QALYs, and save $39.7 billion in formal healthcare costs. For the healthy food incentive, corresponding gains were 3.28 million CVD and 0.12 million diabetes cases prevented, 8.40 million QALYs gained, and $100.2 billion in formal healthcare costs saved, respectively. From a healthcare perspective, both scenarios were cost-effective at 5 years and beyond, with lifetime ICERs of $18,184/QALY (F&V incentive) and $13,194/QALY (healthy food incentive). From a societal perspective including informal healthcare costs and lost productivity, respective ICERs were $14,576/QALY and $9,497/QALY. Results were robust in probabilistic sensitivity analyses and a range of one-way sensitivity and subgroup analyses, including by different durations of the intervention (5, 10, and 20 years and lifetime), food subsidy levels (20%, 50%), insurance groups (Medicare, Medicaid, and dual-eligible), and beneficiary characteristics within each insurance group (age, race/ethnicity, education, income, and Supplemental Nutrition Assistant Program [SNAP] status). Simulation studies such as this one provide quantitative estimates of benefits and uncertainty but cannot directly prove health and economic impacts. CONCLUSIONS: Economic incentives for healthier foods through Medicare and Medicaid could generate substantial health gains and be highly cost-effective.