Advantages of the net benefit regression framework for trial-based economic evaluations of cancer treatments: an example from the Canadian Cancer Trials Group CO.17 trial.

BackgroundEconomic evaluations commonly accompany trials of new treatments or interventions; however, regression methods and their corresponding advantages for the analysis of cost-effectiveness data are not widely appreciated.MethodsTo illustrate regression-based economic evaluation, we review a cost-effectiveness analysis conducted by the Canadian Cancer Trials Group's Committee on Economic Analysis and implement net benefit regression.ResultsNet benefit regression offers a simple option for cost-effectiveness analyses of person-level data. By placing economic evaluation in a regression framework, regression-based techniques can facilitate the analysis and provide simple solutions to commonly encountered challenges (e.g., the need to adjust for potential confounders, identify key patient subgroups, and/or summarize "challenging" findings, like when a more effective regimen has the potential to be cost-saving).ConclusionsEconomic evaluations of patient-level data (e.g., from a clinical trial) can use net benefit regression to facilitate analysis and enhance results

Cost effectiveness of school-located influenza vaccination programs for elementary and secondary school children.

BackgroundStudies have noted variations in the cost-effectiveness of school-located influenza vaccination (SLIV), but little is known about how SLIV's cost-effectiveness may vary by targeted age group (e.g., elementary or secondary school students), or vaccine consent process (paper-based or web-based). Further, SLIV's cost-effectiveness may be impacted by its spillover effect on practice-based vaccination; prior studies have not addressed this issue.MethodsWe performed a cost-effectiveness analysis on two SLIV programs in upstate New York in 2015-2016: (a) elementary school SLIV using a stepped wedge design with schools as clusters (24 suburban and 18 urban schools) and (b) secondary school SLIV using a cluster randomized trial (16 suburban and 4 urban schools). The cost-per-additionally-vaccinated child (i.e., incremental cost-effectiveness ratio (ICER)) was estimated by dividing the incremental SLIV intervention cost by the incremental effectiveness (i.e., the additional number of vaccinated students in intervention schools compared to control schools). We performed deterministic analyses, one-way sensitivity analyses, and probabilistic analyses.ResultsThe overall effectiveness measure (proportion of children vaccinated) was 5.7 and 5.5 percentage points higher, respectively, in intervention elementary (52.8%) and secondary schools (48.2%) than grade-matched control schools. SLIV programs vaccinated a small proportion of children in intervention elementary (5.2%) and secondary schools (2.5%). In elementary and secondary schools, the ICER excluding vaccine purchase was $85.71 and$86.51 per-additionally-vaccinated-child, respectively. When additionally accounting for observed spillover impact on practice-based vaccination, the ICER decreased to $80.53 in elementary schools -- decreasing substantially in secondary schools. (to$53.40). These estimates were higher than the published practice-based vaccination cost (median = $25.50, mean =$45.48). Also, these estimates were higher than our 2009-2011 urban SLIV program mean costs ($65) due to additional costs for use of a new web-based consent system ($12.97 per-additionally-vaccinated-child) and higher project coordination costs in 2015-2016. One-way sensitivity analyses showed that ICER estimates were most sensitive to the SLIV effectiveness.ConclusionsSLIV raises vaccination rates and may increase practice-based vaccination in primary care practices. While these SLIV programs are effective, to be as cost-effective as practice-based vaccination our SLIV programs would need to vaccinate more students and/or lower the costs for consent systems and project coordination.Trial registrationClinicalTrials.gov NCT02227186 (August 25, 2014), updated NCT03137667 (May 2, 2017)

Cost-effectiveness of [18F] fluoroethyl-L-tyrosine for temozolomide therapy assessment in patients with glioblastoma

Background and Purpose: Glioblastomas are the most aggressive of all gliomas. The prognosis of these gliomas, which are classified as grade IV tumors by the World Health Organization (WHO), is poor. Combination therapy, including surgery, radiotherapy, and chemotherapy has variable outcomes and is expensive. In light of rising healthcare costs, there are societal demands for the justification of medical expenses. Therefore, we calculated the cost-effectiveness of follow-up [F-18] fluoroethyl-L-tyrosine ([F-18] FET) positron emission tomography (PET) scans performed on patients with glioblastoma after surgery and before commencing temozolomide maintenance treatment. Materials and Methods: To determine the cost-effectiveness of follow-up [F-18] FET PET procedures, we examined published clinical data and calculated the associated costs in the context of Belgian healthcare. We subsequently performed one-way deterministic sensitivity analysis and Monte Carlo analysis on the calculated ratios. Results: The decision tree based on overall survival rates showed that the number of non-responders identified using PET was 57.14% higher than the number of non-responders identified using conventional MRI. Further, the decision tree based on progression-free survival rates revealed a comparable increase of 57.50% non-responders identified. The calculated cost of two required PET scans per patient during the follow-up treatment phase was 780.50 euros. Two cost-effectiveness ratios were determined for overall survival and progression-free survival rates. Both of these calculations yielded very similar results: incremental cost-effectiveness ratios of 1,365.86 and 1,357.38 euros, respectively, for each identified non-responder. The findings of the sensitivity analysis supported the calculated results, confirming that the obtained data were robust. Conclusion: Our comparative study of conventional MRI and [F-18] FET PET revealed that the latter is a valuable tool for predicting the treatment responses of patients with glioblastomas to follow-up temozolomide maintenance treatment while considering its cost-effectiveness. Thus, [F-18] FET PET scans enable clinical outcomes to be predicted accurately and at a low cost. Moreover, given the robustness of the data in the sensitivity analyses, the level of certainty of this outcome is acceptable

Patient-controlled intravenous morphine analgesia combined with transcranial direct current stimulation for post-thoracotomy pain: A cost-effectiveness study and a feasibility for its future implementation

This prospective randomized study aims to evaluate the feasibility and cost-effectiveness of combining transcranial direct current stimulation (tDCS) with patient controlled intravenous morphine analgesia (PCA-IV) as part of multimodal analgesia after thoracotomy. Patients assigned to the active treatment group (a-tDCS

Cost-Effectiveness of a Comprehensive Approach for Hypertension Control in Low-Income Settings in Argentina: Trial-Based Analysis of the Hypertension Control Program in Argentina

Background: A recent cluster randomized trial evaluating a multicomponent intervention showed significant reductions in blood pressure in low-income hypertensive subjects in Argentina. Objectives: To assess the cost-effectiveness of this intervention. Methods: A total of 1432 hypertensive participants were recruited from 18 primary health care centers. The intervention included home visits led by community health workers, physician education, and text messaging. Resource use and quality of life data using the three-level EuroQol five-dimensional questionnaire were prospectively collected. The study perspective was that of the public health care system, and the time horizon was 18 months. Intention-to-treat analysis was used to analyze cost and health outcomes (systolic blood pressure [SBP] change and quality-adjusted life-years [QALYs]). A 1 time gross domestic product per capita per QALY was used as the cost-effectiveness threshold (US $14,062). Results: Baseline characteristics were similar in the two arms. QALYs significantly increased by 0.06 (95$304 in the intervention group and US $154 in the control group (adjusted difference of US$140.18; 95% CI US $75.41–US$204.94). The incremental cost-effectiveness ratio was $3299 per QALY (95$26 per mm Hg of SBP (95% credible interval 13–46). Subgroup analysis showed that the intervention was cost-effective in all prespecified subgroups (age, sex, cardiovascular risk, and body mass index). Conclusions: The multicomponent intervention was cost-effective for blood pressure control among low-income hypertensive patients.Fil: Augustovski, Federico Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Chaparro, Martin. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Palacios, Alfredo. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Shi, Lizheng. University of Tulane; Estados UnidosFil: Beratarrechea, Andrea Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Irazola, Vilma. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Rubinstein, Adolfo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Mills, Katherine. University of Tulane; Estados UnidosFil: He, Jiang. University of Tulane; Estados UnidosFil: Pichón-Riviere, Andrés. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Cost-effectiveness of community-based screening and treatment of moderate acute malnutrition in Mali.

IntroductionModerate acute malnutrition (MAM) causes substantial child morbidity and mortality, accounting for 4.4% of deaths and 6.0% of disability-adjusted life years (DALY) lost among children under 5 each year. There is growing consensus on the need to provide appropriate treatment of MAM, both to reduce associated morbidity and mortality and to halt its progression to severe acute malnutrition. We estimated health outcomes, costs and cost-effectiveness of four dietary supplements for MAM treatment in children 6-35 months of age in Mali.MethodsWe conducted a cluster-randomised MAM treatment trial to describe nutritional outcomes of four dietary supplements for the management of MAM: ready-to-use supplementary foods (RUSF; PlumpySup); a specially formulated corn-soy blend (CSB) containing dehulled soybean flour, maize flour, dried skimmed milk, soy oil and a micronutrient pre-mix (CSB++; Super Cereal Plus); Misola, a locally produced, micronutrient-fortified, cereal-legume blend (MI); and locally milled flour (LMF), a mixture of millet, beans, oil and sugar, with a separate micronutrient powder. We used a decision tree model to estimate long-term outcomes and calculated incremental cost-effectiveness ratios (ICERs) comparing the health and economic outcomes of each strategy.ResultsCompared to no MAM treatment, MAM treatment with RUSF, CSB++, MI and LMF reduced the risk of death by 15.4%, 12.7%, 11.9% and 10.3%, respectively. The ICER was US$9821 per death averted (2015 USD) and US$347 per DALY averted for RUSF compared with no MAM treatment.ConclusionMAM treatment with RUSF is cost-effective across a wide range of willingness-to-pay thresholds.Trial registrationNCT01015950

Cost-effectiveness of a patient-centred approach to managing multimorbidity in primary care:a pragmatic cluster randomised controlled trial

Objective Patients with multiple chronic health conditions are often managed in a disjointed fashion in primary care, with annual review clinic appointments offered separately for each condition. This study aimed to determine the cost-effectiveness of the 3D intervention, which was developed to improve the system of care. Design Economic evaluation conducted alongside a pragmatic cluster-randomised trial. Setting General practices in three centres in England and Scotland. Participants 797 adults with three or more chronic conditions were randomised to the 3D intervention, while 749 participants were randomised to receive usual care. Intervention The 3D approach: comprehensive 6-monthly general practitioner consultations, supported by medication reviews and nurse appointments. Primary and secondary outcome measures The primary economic evaluation assessed the cost per quality-adjusted life year (QALY) gained from the perspective of the National Health Service (NHS) and personal social services (PSS). Costs were related to changes in a range of secondary outcomes (QALYs accrued by both participants and carers, and deaths) in a cost-consequences analysis from the perspectives of the NHS/PSS, patients/carers and productivity losses. Results Very small increases were found in both QALYs (adjusted mean difference 0.007 (-0.009 to 0.023)) and costs (adjusted mean difference 126 pound (-739 pound to 991)) pound in the intervention arm compared with usual care after 15 months. The incremental cost-effectiveness ratio was 18 pound 499, with a 50.8% chance of being cost-effective at a willingness-to-pay threshold of 20 pound 000 per QALY (55.8% at 30 pound 000 per QALY). Conclusions The small differences in costs and outcomes were consistent with chance, and the uncertainty was substantial; therefore, the evidence for the cost-effectiveness of the 3D approach from the NHS/PSS perspective should be considered equivocal

Monoclonal antibodies in type 2 asthma : a systematic review and network meta-analysis

Since novel treatments to target eosinophilic inflammation in Type 2 asthma are emerging, we aimed to evaluate and meta-analyze the efficacy of monoclonal antibodies to reduce exacerbation rate. PubMed and Web of Science were searched for phase II and phase III randomized clinical trials with monoclonal antibodies targeting key mediators of type 2-associated asthma. Thirty trials were selected involving biologics that target the IL-5 pathway, IL-13, the common IL-4 and IL-13 receptor, IL-9, IL-2 and TSLP. As no head-to-head trials were retrieved from literature, we performed an arm-based network meta-analysis to compare effects on exacerbation rate between the different treatments. Mepolizumab, reslizumab and benralizumab significantly reduced the risk of exacerbations compared to placebo (by 47-52%, 50-60%, and 28-51% respectively). Reslizumab and benralizumab also improved lung function. Dupilumab and tezepelumab improved lung function in frequent exacerbators. Lebrikizumab had no significant effect on the number of exacerbations, symptom control or health-related quality of life. Tralokinumab improved lung function compared to placebo. Network meta-analysis of all treatment and placebo arms, showed no superiority of one biologic over the others. Large reductions in exacerbation rates were observed compared to placebo, though only benralizumab was sufficiently powered (n = 2051) to demonstrate significantly decreased exacerbation rates in the subgroup analysis of IL-5 acting agents compared to placebo. Monoclonal antibodies such as mepolizumab, reslizumab and benralizumab have proven their benefit to reduce exacerbation rates in severe persistent eosinophilic asthma in the published trials. However, no statistically significant superiority was observed of one biologic over the other in the network meta-analysis. More studies with direct head to head comparisons and better defined endotypes are required

Evaluating the cost-effectiveness of existing needle and syringe programmes in preventing hepatitis C transmission in people who inject drugs

AIM: To evaluate the cost-effectiveness of needle and syringe programmes (NSPs) compared with no NSPs on hepatitis C virus (HCV) transmission in the United Kingdom. DESIGN: Cost-effectiveness analysis from a National Health Service (NHS)/health-provider perspective, utilizing a dynamic transmission model of HCV infection and disease progression, calibrated using city-specific surveillance and survey data, and primary data collection on NSP costs. The effectiveness of NSPs preventing HCV acquisition was based on empirical evidence. SETTING AND PARTICIPANTS: UK settings with different chronic HCV prevalence among people who inject drugs (PWID): Dundee (26%), Walsall (18%) and Bristol (45%) INTERVENTIONS: Current NSP provision is compared with a counterfactual scenario where NSPs are removed for 10 years and then returned to existing levels with effects collected for 40 years. MEASUREMENTS: HCV infections and cost per quality-adjusted life year (QALY) gained through NSPs over 50 years. FINDINGS: Compared with a willingness-to-pay threshold of £20 000 per QALY gained, NSPs were highly cost-effective over a time-horizon of 50 years and decreased the number of HCV incident infections. The mean incremental cost-effectiveness ratio was cost-saving in Dundee and Bristol, and £596 per QALY gained in Walsall, with 78, 46 and 40% of simulations being cost-saving in each city, respectively, with differences driven by coverage of NSP and HCV prevalence (lowest in Walsall). More than 90% of simulations were cost-effective at the willingness-to-pay threshold. Results were robust to sensitivity analyses, including varying the time-horizon, HCV treatment cost and numbers of HCV treatments per year. CONCLUSIONS: Needle and syringe programmes are a highly effective low-cost intervention to reduce hepatitis C virus transmission, and in some settings they are cost-saving. Needle and syringe programmes are likely to remain cost-effective irrespective of changes in hepatitis C virus treatment cost and scale-up

An Exploratory Study of Suboxone (Buprenorphine/ Naloxone) Film Splitting: Cutting Methods, Content Uniformity, and Stability

Suboxone films are U.S. Food and Drug Administration approved to treat opioid dependence. While the package insert states that films should not be cut, physicians often prescribe film fractions for treatment and tapering. There is no data to support this practice, and this study was initiated to evaluate cutting methods, content uniformity, and stability of split films. Suboxone 8-mg buprenorphine/2-mg naloxone films were split using four methods: 1) ruler/razor cut, 2) scissor cut, 3) fold/rip, and 4) fold/scissor cut. United States Pharmacopeia Chapter \u3c905\u3e was used to evaluate the weight variation and content uniformity of split films. The stability of split films stored in polybags was evaluated over 7 days. A stability-indicating high-performance liquid chromatography method was used for content uniformity and stability evaluation. The weight variation results were acceptable for the half films from all four cutting methods, but this was not true for the quarter films. The method of ruler/razor cut was determined most favorable and used for the content uniformity test. Based on the high-performance liquid chromatography results, the half films from the ruler/razor cut method met the passing criteria of United States Pharmacopeia Chapter \u3c905\u3e with acceptance values of 9.8 to 10.4 for buprenorphine and 8.4 to 11.5 for naloxone (≤15 is considered passing). The stability results indicated that both actives retained \u3e97.7% of initial strength. Four cutting methods were found to be acceptable for splitting Suboxone films into half but not quarter fractions. The half films from the ruler/razor cut method also passed United States Pharmacopeia Chapter \u3c905\u3e content uniformity test. Both actives remained stable for 7 days when the half films were stored in polybags at room temperature