Cost-effectiveness of ivosidenib versus chemotherapy for previously treated IDH1-mutant advanced intrahepatic cholangiocarcinoma in Taiwan.

BACKGROUND: International guidelines recommend ivosidenib followed by modified FOLFOX (mFOLFOX) for advanced intrahepatic cholangiocarcinoma (ICC) with isocitrate dehydrogenase 1 (IDH1) mutations. Taiwan National Health Insurance covers only fluorouracil/leucovorin (5-FU/LV) chemotherapy for this ICC group, and there has been no prior economic evaluation of ivosidenib. Therefore, we aimed to assess ivosidenib's cost-effectiveness in previously treated, advanced ICC-presenting IDH1 mutations compared with mFOLFOX or 5-FU/LV. METHODS: A 3-state partitioned survival model was employed to assess ivosidenib's cost-effectiveness over a 10-year horizon with a 3% discount rate, setting the willingness-to-pay threshold at 3 times the 2022 GDP per capita. Efficacy data for Ivosidenib, mFOLFOX, and 5-FU/LV were sourced from the ClarIDHy, ABC06, and NIFTY trials, respectively. Ivosidenib's cost was assumed to be NT$10,402/500 mg. Primary outcomes included incremental cost-effectiveness ratios (ICERs) and net monetary benefit. Deterministic sensitivity analyses (DSA) and probabilistic sensitivity analyses (PSA) were employed to evaluate uncertainty and explore price reduction scenarios. RESULTS: Ivosidenib exhibited ICERs of NT$6,268,528 and NT$5,670,555 compared with mFOLFOX and 5-FU/LV, respectively, both exceeding the established threshold. PSA revealed that ivosidenib was unlikely to be cost-effective, except when it was reduced to NT$4,161 and NT$5,201/500 mg when compared with mFOLFOX and 5-FU/LV, respectively. DSA underscored the significant influence of ivosidenib's cost and utility values on estimate uncertainty. CONCLUSIONS: At NT$10,402/500 mg, ivosidenib was not cost-effective for IDH1-mutant ICC patients compared with mFOLFOX or 5-FU/LV, indicating that a 50-60% price reduction is necessary for ivosidenib to be cost-effective in this patient group.

Environmental and economic concerns surrounding restrictions on glyphosate use in corn.

Since the commercialization of transgenic glyphosate-tolerant (GT) crops in the mid-1990s, glyphosate has become the dominant herbicide to control weeds in corn, soybean, and other crops in the United States and elsewhere. However, recent public concerns over its potential carcinogenicity in humans have generated calls for glyphosate-restricting policies. Should a policy to restrict glyphosate use, such as a glyphosate tax, be implemented? The decision involves two types of tradeoffs: human health and environmental (HH-E) impacts versus market economic impacts, and the use of glyphosate versus alternative herbicides, where the alternatives potentially have more serious adverse HH-E effects. Accounting for farmers' weed management choices, we provide empirical evaluation of the HH-E welfare and market economic welfare effects of a glyphosate use restriction policy on US corn production. Under a glyphosate tax, farmers would substitute glyphosate for a combination of other herbicides. Should a 10% glyphosate tax be imposed, then the most conservative welfare estimate is a net HH-E welfare gain with a monetized value of US$6 million per annum but also a net market economic loss of US$98 million per annum in the United States, which translates into a net loss in social welfare. This result of overall welfare loss is robust to a wide range of tax rates considered, from 10 to 50%, and to multiple scenarios of glyphosate's HH-E effects, which are the primary sources of uncertainties about glyphosate's effects.

Medication use evaluation of the financial and clinical implications of ixazomib compared to bortezomib in the outpatient setting.

In the past decade, several new therapies have been approved for use in multiple myeloma, including the novel oral agent, ixazomib. Ixazomib, like bortezomib and carfilzomib, is a proteasome inhibitor, a class of agents that are a mainstay of treating multiple myeloma in both the frontline and relapsed settings. Ixazomib is administered orally and offers many potential advantages over the subcutaneous or intravenous administration of bortezomib. In this single-center, retrospective medication use evaluation, adult patients with multiple myeloma receiving either ixazomib or bortezomib in the outpatient setting were assessed to evaluate financial implications and tolerability. A total of 28 patients were included. The total wholesale acquisition cost for one cycle of ixazomib was $9942, and $6412 for bortezomib. Average reimbursement per cycle was $9205 for ixazomib and $5664 for bortezomib. Secondarily, the incidence of interruption in therapy was evaluated. Ixazomib was associated with a slightly higher incidence of interruption compared to bortezomib, 42.9% and 35.7%, respectively. It is notable that ixazomib has similar drug reimbursement rates to bortezomib, but slightly higher rates of interruption in therapy. In conclusion, if tolerable for the patient, ixazomib may offer a financially acceptable alternative for the treatment of multiple myeloma.

The efficacy and economic evaluation of roxadustat treatment for anemia in patients with kidney disease not receiving dialysis.

BACKGROUND: This study aimed to assess the efficacy, tolerance, and cost-effectiveness of roxadustat treatment for anemia in patients with chronic kidney disease not receiving dialysis (CKD ND). METHODS: A meta-analysis was conducted to evaluate the clinical efficacy and tolerance of roxadustat for the correction of anemia associated with CKD ND, and a Markov model was developed to evaluate the cost-effectiveness of roxadustat compared with a placebo. RESULTS: The meta-analysis results showed that compared with a placebo, roxadustat treatment was associated with a remarkably higher rate of clinical response and the differences in the rate of adverse events between these two regimens were not significant. Moreover, roxadustat treatment (70 mg, three times per week) provided an additional 0.49 QALYs at a cost of $12,526 in the time horizon of 5 years, resulting in an ICER of $25,563 per QALY, with approximately 60% probability to be cost-effective at a $29,295 per QALY willingness-to-pay (WTP) threshold from the perspective of Chinese medical system. CONCLUSION: For the treatment of anemia in Chinese patients with CKD ND, roxadustat is much more effective than a placebo; moreover, it is cost-effective at conventional WTP thresholds.

Real-world treatment patterns, resource use and cost burden of multiple myeloma in Portugal.

OBJECTIVE: We provide a real-world overview of multiple myeloma (MM) treatment patterns, outcomes and healthcare resource use (HRU) in Portugal. METHODS: Data were collected retrospectively from consecutive patients diagnosed/treated at the Portuguese Oncology Institute of Porto (IPO-Porto) between 2012 and 2015. Primary objectives were progression-free survival (PFS) and overall survival (OS), with treatment patterns and HRU secondary. Analysis was by line of therapy (LOT), and post hoc by age (<65/≥65 years). RESULTS: 165, 73 and 32 patients received first, second and third LOTs respectively (N = 187). OS probabilities were 91.5%, 83.2% (<65 years) and 86.6%, 65.3% (≥65 years) at 12, 24 months respectively. PFS decreased from the start of each LOT for both age groups and was less for patients ≥65 years. Younger patients received more combination treatment (immunomodulatory drugs + proteasome inhibitors) and stem cell transplants, and had higher mean costs than older patients (€81,213 vs. €36,864 where three LOTs were received). Cost drivers were medications, transplantations and hospitalisations. CONCLUSION: Our results suggest divergence between younger and older MM patients. Older patients had lower OS and PFS probabilities, HRU costs and fewer stem cell transplantations. The treatment patterns in each LOT may differ from other countries' findings, suggesting treatment heterogeneity.

Healthcare resource utilization with ixazomib or placebo plus lenalidomide-dexamethasone in the randomized, double-blind, phase 3 TOURMALINE-MM1 study in relapsed/refractory multiple myeloma.

AIMS: The aim of this analysis was to assess healthcare resource utilization in the pivotal phase 3 TOURMALINE-MM1 study of the oral proteasome inhibitor ixazomib or placebo plus lenalidomide and dexamethasone (Rd) in relapsed and/or refractory multiple myeloma (RRMM). METHODS: In this double-blind, placebo-controlled, randomized study (NCT01564537), 722 patients with RRMM following 1-3 prior lines of therapy received Rd plus ixazomib (ixazomib-Rd; n = 360) or matching placebo (placebo-Rd; n = 362) until disease progression or unacceptable toxicity. Healthcare resource utilization data were captured on Day 1 of each 28-day cycle, every 4 weeks during follow-up for progression-free survival, and every 12 weeks during subsequent follow-up, and included medical encounters (length of stay, inpatient, outpatient, and reason) and number of missing days from work or other activities for patients and caregivers. RESULTS: Exposure-adjusted rates of hospitalization were similar between the ixazomib-Rd and placebo-Rd arms, at 0.530 and 0.564 per patient year (ppy), respectively, as were outpatient visit rates (3.305 and 3.355 ppy). Mean length of hospitalization per patient was 10.0 and 10.8 days, respectively. In both arms, hospitalization and outpatient visit rates were higher in patients with two or three prior lines of treatment (ixazomib-Rd: 0.632 and 3.909 ppy; placebo-Rd: 0.774 and 3.539 ppy) compared with patients with one prior line (ixazomib-Rd: 0.460 and 2.888 ppy; placebo-Rd: 0.436 and 3.243 ppy). Patients and their caregivers who missed any work or other activity missed a median of 7 and 5 days in the ixazomib-Rd arm, respectively, vs 8 and 4 days with placebo-Rd. LIMITATIONS: The study was not powered for a statistical comparison of healthcare resource utilization between treatment arms, nor did it capture costs associated with utilization of the identified healthcare resources. CONCLUSIONS: This pre-specified analysis demonstrated that the all-oral triplet regimen of ixazomib added to Rd did not increase healthcare resource utilization compared with placebo-Rd.

Ixazomib for Relapsed or Refractory Multiple Myeloma: Review from an Evidence Review Group on a NICE Single Technology Appraisal.

Ixazomib is an oral proteasome inhibitor used in combination with lenalidomide plus dexamethasone (IXA-LEN-DEX) and licensed for relapsed or refractory multiple myeloma. As part of a single technology appraisal (ID807) undertaken by the National Institute of Health and Care Excellence, the Evidence Review Group, Warwick Evidence was invited to independently review the evidence submitted by the manufacturer of ixazomib, Takeda UK Ltd. The main source of clinical effectiveness data about IXA-LEN-DEX came from the Tourmaline-MM1 randomized controlled trial in which 771 patients with relapsed or refractory multiple myeloma received either IXA-LEN-DEX or placebo-LEN-DEX as their second-, third-, or fourth-line treatment. Takeda estimated the cost effectiveness of IXA-LEN-DEX using a de-novo partitioned-survival model with three health states (pre-progression, post-progression, and dead). In their first submission, this model was used to estimate the cost effectiveness of IXA-LEN-DEX vs. bortezomib plus dexamethasone (BORT-DEX) in second-line treatment, and of IXA-LEN-DEX vs. LEN-DEX in third-line treatment. To estimate the relative clinical performance of IXA-LEN-DEX vs. BORT-DEX, Takeda conducted network meta-analyses for important outcomes. The network meta-analysis for overall survival was found to be flawed in several respects, but mainly because a hazard ratio input for one of the studies in the network had been inverted, resulting in a large inflation of the claimed superiority of IXA-LEN-DEX over BORT-DEX and a considerable overestimation of its cost effectiveness. In subsequent submissions, Takeda withdrew second-line treatment as an option for IXA-LEN-DEX. The manufacturer's first submission comparing IXA-LEN-DEX with LEN-DEX for third-line therapy employed Tourmaline-MM1 data from third- and fourth-line patients as proxy for a third-line population. The appraisal committee did not consider this reasonable because randomization in Tourmaline-MM1 was stratified according to one previous treatment and two or more previous treatments. A further deficiency was considered to be the manufacturer's use of interim survival data rather than the most mature data available. A second submission from the company focussed on IXA-LEN-DEX vs. LEN-DEX as third- or fourth-line treatment (the two or more previous lines population) and a new patient access scheme was introduced. Covariate modeling of survival outcomes was proposed using the most mature survival data. The Evidence Review Group's main criticisms of the new evidence included: the utility associated with the pre-progression health state was overestimated, treatment costs of ixazomib were underestimated, survival models were still associated with great uncertainty, leading to clinically implausible anomalies and highly variable incremental cost-effectiveness ratio estimates, and the company had not explored a strong assumption that the survival benefit of IXA-LEN-DEX over LEN-DEX would be fully maintained for a further 22 years beyond the observed data, which encompassed only approximately 2.5 years of observation. The appraisal committee remained unconvinced that ixazomib represented a cost-effective use of National Health Service resources. Takeda's third submission offered new base-case parametric models for survival outcomes, a new analysis of utilities, and proposed a commercial access agreement. In a brief critique of the third submission, the Evidence Review Group agreed that the selection of appropriate survival models was problematic and at the request of the National Institute for Health Care and Excellence investigated external sources of evidence regarding survival outcomes. The Evidence Review Group considered that some cost and utility estimates in the submission may have remained biased in favor of ixazomib. As a result of their third appraisal meeting, the committee judged that for the two to three prior therapies population, and at the price agreed in a commercial access agreement, ixazomib had the potential to be cost effective. It was referred to the Cancer Drugs Fund so that further data could accrue with the aim of diminishing the clinical uncertainties.

Composite hollow fiber nanofiltration membranes for recovery of glyphosate from saline wastewater.

A high performance versatile composite hollow fiber nanofiltration (NF) membrane is reported for the separation of glyphosate from saline waste streams. Preparation of SPEEK based on an amorphous poly (ether ether ketone, PEEK) was investigated. The membrane was prepared by coating sulfonated polyether ether ketone (SPEEK) onto a polyethersulfone (PES) ultrafiltration (UF) hollow fiber membrane. The composite membrane was characterized by water permeability, scanning electron microscopy, and rejection toward sodium sulfate (Na2SO4), sodium chloride (NaCl), and calcium chloride (CaCl2). About 90% rejection toward sulfate anions and only 10% rejection for calcium cations were obtained. A water permeability around 10-13 LMHBar and 90% rejection for polyethylene glycol (PEG) with a molecular weight of 4000-6000 Da were observed. In the separation of glyphosate from saline wastewater, the membrane rejected less than 20% of NaCl and higher than 90% of glyphosate at an operating pressure of 5 bars and pH = 11.0. An economic analysis indicated that the cost for recovery of glyphosate was comparably low to the value gained by an increase in the productivity. The results may lead to a new promising low energy solution for the environmental problem faced by the herbicide industry.

Herbicide-resistant weed management: focus on glyphosate.

This review focuses on proactive and reactive management of glyphosate-resistant (GR) weeds. Glyphosate resistance in weeds has evolved under recurrent glyphosate usage, with little or no diversity in weed management practices. The main herbicide strategy for proactively or reactively managing GR weeds is to supplement glyphosate with herbicides of alternative modes of action and with soil-residual activity. These herbicides can be applied in sequences or mixtures. Proactive or reactive GR weed management can be aided by crop cultivars with alternative single or stacked herbicide-resistance traits, which will become increasingly available to growers in the future. Many growers with GR weeds continue to use glyphosate because of its economical broad-spectrum weed control. Government farm policies, pesticide regulatory policies and industry actions should encourage growers to adopt a more proactive approach to GR weed management by providing the best information and training on management practices, information on the benefits of proactive management and voluntary incentives, as appropriate. Results from recent surveys in the United States indicate that such a change in grower attitudes may be occurring because of enhanced awareness of the benefits of proactive management and the relative cost of the reactive management of GR weeds.

Economic impacts of glyphosate-resistant crops.

Glyphosate-resistant crops have been widely planted since their introduction in 1996. Growers have numerous choices for herbicide treatments and have chosen to plant glyphosate-resistant crops on the basis of economic factors. The economic effects of the widespread planting of glyphosate-resistant crops have included reductions in herbicide expenses, increases in seed costs, increased yield and changes in the relative profitability of crops that has resulted in changes in which crops are planted. In addition, non-pecuniary benefits have accrued as a result of the simplicity of weed management in the glyphosate-resistant crop systems.

The economical efficiency of classic and no-tillage system at genetical modified soybean in conditions of Romania.

The technology of maize without plough land possible to apply in USA and other countries with advanced agriculture, only by atrazine and simazine herbicides synthesis by J. Geigy Company from Switzerland Phillips and Young (1973) said in their book that in USA is practicing no-tillage system on millions acres. After recently dates published by Derpsh (2001) in USA no-tillage is practice on 21,120,000 ha, in Brazil on 14,330,000 ha, in Argentina 10,500,000 ha etc. The chernozem soil in Romania is very properly for no-tillage system. First experiments with no-tillage system have been since 1965 at maize, and at soybean since 2002 until 2005, obtaining remarkable results concerning maize and soybean yields. At genetically modified soybean crop the economic efficiency is very big because fuel consumption was 75 l/ha at classic system and only 21 l/ha at no-tillage system. The expenses with mechanical working were 217 Euro/ha at classic system and only 45 Euro/ha at no-tillage system.

Labeling DNA with stable isotopes: economical and practical considerations.

Labeling DNA with stable isotopes to measure cell proliferation can be a technique as effective as 3H-thymidine labeling without the limitations imposed by using radioisotopes. Here, we investigated the relative efficiency of four nonradioactive precursors to DNA: [1-13C]-glycine, [1,2-13C2]-glycine, [U-13C]-glucose, and [U-13C, 15N]-thymidine. The efficiency of incorporation for each of these labeled precursors in HEP G2 cells in culture has been studied. When considering the actual costs of in vivo experiments in which large doses of labeled material are needed, economical constraints may play an important role in defining a practical method. Therefore, the economics of this process were also considered. Using the enrichment per dollar for whichever nucleoside had the highest incorporation in a given experiment, glycine is about five times more economical as a label than thymidine and eight times more economical than glucose in these cells.