The study aimed to assess the cost-effectiveness of sintilimab combined with cisplatin plus paclitaxel versus chemotherapy alone as first-line treatment in patients with advanced or metastatic ...esophageal squamous cell carcinoma from the Chinese healthcare system.
A partitioned survival model was developed based on the ORIENT-15 clinical trial. Drug costs and health state utility were obtained from the literature. Outcomes included the health outcomes in life-years, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio. One-way and probabilistic sensitivity analyses were performed to evaluate the model uncertainty.
In overall population, patients given sintilimab plus chemotherapy gained more health benefits (0.90 QALYs vs. 0.61 QALYs), and the cost was more (15,399.21 US$ VS. 7475.58 US$) than that for patients in the chemotherapy group. In the subgroup, patients given sintilimab plus chemotherapy gained more health benefits (0.89 QALYs vs. 0.68 QALYs), and the cost was more (15,656.19 US$ vs. 9,162.77 US$) than that for patients in the chemotherapy group. Compared with chemotherapy, patients receiving sintilimab plus chemotherapy had ICERs of $26,773.68/QALY in the overall population and $30,065.50/QALY in the subgroup, which was above the threshold of WTP.
Sintilimab plus chemotherapy was more cost-effective than chemotherapy alone for patients with advanced esophageal cancer from the perspective of the Chinese healthcare system.
BACKGROUNDThe rising cost of cancer drug therapy threatens the long-term sustainability of Taiwan National Health Insurance. Cost savings can be achieved through various strategies, e.g., using ...smaller vial sizes, sharing vials, weight-based dosing, or switching to biosimilars. Here we aimed to examine the cost-effectiveness of a trastuzumab biosimilar combined with docetaxel (TDbiol) for treatment-naïve HER2+ metastatic breast cancer (MBC), and the financial impact of drug wastage. METHODSA Markov model with three health states was developed to assess the cost-effectiveness of trastuzumab biosimilars plus docetaxel over a 40-month time horizon in patients with HER2+ MBC. Based on the literature and our expert opinion, we assumed similar efficacy between the trastuzumab biosimilar and its reference product. The primary clinical input for the biosimilar was the same as for the reference product in the Catastrophic Patient Database (HV). Health state utilities were derived from the literature, and direct medical costs were obtained from the National Health Insurance Administration (NHIA). RESULTSIn the base-case scenario, the incremental cost-effectiveness ratio (ICER) was NTD 811,050 per QALY gained. One-way sensitivity analyses showed that the model was sensitive to utilities and transition probabilities, but not particularly sensitive to the wastage assumption. In scenario analyses, the ICER was higher when applying the price for trastuzumab reference biologic (branded), than for trastuzumab biosimilar. CONCLUSIONThe trastuzumab biosimilar combination regimen is cost-effective and offers significant drug cost savings in Taiwan.
Environmental levels of platinum group elements (PGEs) are rising due to emissions of vehicle catalytic converter (VCC) materials containing palladium, platinum and rhodium. When these PGE-containing ...VCC materials are exposed to soil and water, coordination complex formation with ligands present in the environment may mobilize PGEs into solution, particularly Pd. Road de-icing salt contains two ligands with high affinities for Pd2+: chloride (Cl−) from NaCl and cyanide (CN−) from ferrocyanide (Fe(CN)64−) anti-caking agents. Batch leaching studies of VCC materials were conducted with solutions representative of de-icer-contaminated road runoff at pH 8 and room temperature for 48 h. Ferrocyanide (FC) concentrations of 0 μM, 1 μM, 2 μM and 10 μM were tested with background electrolyte concentrations of 0.028 M NaCl (1000 mg/L Cl−) or 0.028 M NaClO4. Palladium release increased with FC concentration, ranging from 0.014 ± 0.002 μM Pd without FC to 5.013 ± 0.002 μM Pd at 10 μM FC. At 0 μM, 1 μM and 2 μM FC, chloride induced further Pd release, but had no effect at 10 μM FC. PHREEQC modeling predicted that the predominant species present in equilibrium with Pd(OH)2(s) were Pd(OH)20 and Pd(CN)42−, and that PdClx2−x complexes had only a minor effect on the total concentration of dissolved palladium. The effect of FC on Pd release was predicted but not the effect of Cl−, indicating possible kinetic control. Platinum was measured above limits of detection (LODs) only at 10 μM FC, and rhodium levels were below LODs, consistent with their slower complexation kinetics.
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•Road de-icing salt causes catalytic converter materials to release palladium.•Anti-caking agent (ferrocyanide) from de-icer has dominant effect on Pd release.•Chloride combined with ferrocyanide synergistically boosts palladium release.•Platinum release insignificant except at highest levels of ferrocyanide.
The English National Institute for Health and Care Excellence (NICE) and the Australian Pharmaceutical Benefits Advisory Committee (PBAC) require evidence that a new medicine represents value for ...money before being publicly funded. NICE has an explicit threshold for cost effectiveness, whereas PBAC does not. We compared the initial incremental cost-effectiveness ratios (ICERs) presented by manufacturers in matched submissions to each decision-making body, with the aim of exploring the impact of an explicit threshold on these ICERs.
Data were extracted from matched submissions from 2005 to 2015. The ICERs in these submissions were compared within each pair and with respect to a cost-effectiveness threshold.
Fifty-eight pairs of matched submissions were identified. The median difference between the ICERs ($2635/quality-adjusted life year QALY) was significantly greater than zero (Wilcoxon signed-rank test, P = 0.0299), indicating that the proposed ICERs in the submissions to NICE were higher than those in the matched submissions to PBAC. On 93% of occasions, NICE ICERs were within –$17,772 to +$48,422 of the corresponding PBAC ones (Bland-Altman analysis), demonstrating poor agreement. When an implicit threshold of AUD$50,000/QALY was assumed for PBAC decision making, only eight pairs of submissions had discordant ICERs falling above or below the respective threshold.
The significantly higher ICERs in the submissions to NICE than those to PBAC may be a consequence of NICE’s explicit willingness-to-pay threshold, and/or other health system factors. Industry may be assuming an implicit threshold for PBAC when constructing their ICERs despite the lack of acknowledgement of such a threshold.
In this paper, we developed HIV/AIDS mathematical model which comprises important compartments such as individuals with aware and unaware susceptible, undiagnosed HIV infections, diagnosed HIV ...infectious with and without AIDS symptom, and treated from the disease. This model considers the rate of becoming aware and unaware as a function of media campaign, whereas screening and treatments rates are constants. The effective reproduction number, equilibria and their nature of stability were formulated. The bifurcation also occurred when the effective reproduction number is equal to unity. This model extended to a new model which incorporates interventions such as preventive, screening, and treatment strategies. In this model the optimal control problem is formulated and solved analytically. In addition to this the optimality system is derived and solved numerically using the forward-backward sweep method (FBSM). Finally the cost-effectiveness of these combination controlling strategies is derived.
Abstract
Aims
Phosphodiesterase 2 A (Pde2A), a cAMP-hydrolysing enzyme, is essential for mouse development; however, the cause of Pde2A knockout embryonic lethality is unknown. To understand whether ...Pde2A plays a role in cardiac development, hearts of Pde2A deficient embryos were analysed at different stage of development.
Methods and results
At the stage of four chambers, Pde2A deficient hearts were enlarged compared to the hearts of Pde2A heterozygous and wild-type. Pde2A knockout embryos revealed cardiac defects such as absence of atrial trabeculation, interventricular septum (IVS) defects, hypertrabeculation and thinning of the myocardial wall and in rare cases they had overriding aorta and valves defects. E14.5 Pde2A knockouts showed reduced cardiomyocyte proliferation and increased apoptosis in the IVS and increased proliferation in the ventricular trabeculae. Analyses of E9.5 Pde2A knockout embryos revealed defects in cardiac progenitor and neural crest markers, increase of Islet1 positive and AP2 positive apoptotic cells. The expression of early cTnI and late Mef2c cardiomyocyte differentiation markers was strongly reduced in Pde2A knockout hearts. The master transcription factors of cardiac development, Tbx, were down-regulated in E14.5 Pde2A knockout hearts. Absence of Pde2A caused an increase of intracellular cAMP level, followed by an up-regulation of the inducible cAMP early repressor, Icer in fetal hearts. In vitro experiments on wild-type fetal cardiomyocytes showed that Tbx gene expression is down-regulated by cAMP inducers. Furthermore, Pde2A inhibition in vivo recapitulated the heart defects observed in Pde2A knockout embryos, affecting cardiac progenitor cells. Interestingly, the expression of Pde2A itself was dramatically affected by Pde2A inhibition, suggesting a potential autoregulatory loop.
Conclusions
We demonstrated for the first time a direct relationship between Pde2A impairment and the onset of mouse congenital heart defects, highlighting a novel role for cAMP in cardiac development regulation.
Outcomes based payments contracting is in its infancy. The increased attention being given to rare disease place a premium on the ability to engage with payers to ensure that there is an analytical ...framework relevant to value claims contracting. Rare disease is not, of course, alone; many other chronic disease states may be suitable candidates and have been over the past 10 years or more. Rare disease, however stands apart: (i) the evidence base at product launch is limited; (ii) the therapy costs are often considered prohibitive; and (iii) the target patient population is small. At the same time, those seeking to implement an evidence-based engagement with health systems to support innovative rare disease interventions face a substantive technology assessment barrier. The focus in health technology assessment on assumption driven modeled cost-effectiveness simulations that support imaginary recommendations for cost-effective pricing and access is, however, an avoidable barrier. In the US, this barrier is the business model of the Institute for Clinical and Economic Review (ICER) and one endorsed by the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Rare disease can be better served with other tools at our disposal with a proposed new start analytical framework in health technology assessment. The purpose of this brief note is to make the case that this proposed new start focused on single attribute value claims that meet the standards of normal science and fundamental evidence can not only dispense with the ICER imaginary modeling but, with a new start formulary submission package, integrate value claims with assessment protocols to set the stage for effective outcome-based contracting as the default standard for future payer negotiations.
The focus of this commentary is on the attempt to create EQ-5D-3L ordinal preferences from a disease specific asthma questionnaire, the Asthma Quality of Life Questionnaire (AQLQ). The question is ...whether it is possible from the perspective of fundamental measurement to create a simple linear algorithm to map AQLQ scores to EQ-5D-3L preferences. It is proposed that this is mathematically impossible as the aggregate AQLQ score is ordinal, apart from the fact that the AQLQ is a multiattribute score that lacks construct validity and any pretense to having interval properties. Disallowing the mapped utilities means that the modelling cannot be sustained. It is proposed that the focus should be on single attribute measures of the latent construct "need fulfillment quality of life". These measures would meet the required standards of Rasch Measurement Theory (RMT) applying simultaneous conjoint standards of measurement theory, as well as capturing the patient voice.
Abstract
Background
Irritable bowel syndrome (IBS) is a common, often disabling gastrointestinal (GI) disorder for which there is no satisfactory medical treatment but is responsive to cognitive ...behavior therapy (CBT).
Purpose
To evaluate the costs and cost-effectiveness of a minimal contact version of CBT (MC-CBT) condition for N = 145 for IBS relative to a standard, clinic-based CBT (S-CBT; N = 146) and a nonspecific comparator emphasizing education/support (EDU; N = 145).
Method
We estimated the per-patient cost of each treatment condition using an activity-based costing approach that allowed us to identify and estimate costs for specific components of each intervention as well as the overall total costs. Using simple means analysis and multiple regression models, we estimated the incremental effectiveness of MC-CBT relative to S-CBT and EDU. We then evaluated the cost-effectiveness of MC-CBT relative to these alternatives for selected outcomes at immediate posttreatment and 6 months posttreatment, using both an intent-to-treatment and per-protocol methodology. Key outcomes included scores on the Clinical Global Impressions-Improvement Scale and the percentage of patients who positively responded to treatment.
Results
The average per-patient cost of delivering MC-CBT was $348, which was significantly less than the cost of S-CBT ($644) and EDU ($457) (p < .01). Furthermore, MC-CBT produced better average patient outcomes at immediate and 6 months posttreatment relative to S-CBT and EDU (p < .01). The current findings indicated that MC-CBT is a cost-effective option relative to S-CBT and EDU.
Conclusion
As predicted, MC-CBT was delivered at a lower cost per patient than S-CBT and performed better over time on the primary outcome of global IBS symptom improvement.
A largely home-based regimen of cognitive behavioral therapy for irritable bowel syndrome was delivered at a lower cost per patient than traditional office-based CBT and performed better over time in relieving core gastrointestinal symptoms (e.g., abdominal pain, altered bowel habits such as diarrhea and/or constipation) refractory to conventional medical treatments.
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