Evaluation of changes in the clinical benefits of oncology drugs over time following reimbursement using the ASCO-VF and the ESMO-MCBS.

PURPOSE: This study aims to estimate changes in the value of oncology drugs over time from initial data of the reimbursement decisions to subsequent publications in Korea, using two value frameworks. METHODS: We retrieved primary publications assessed for reimbursement between 2007 and July 2021 from the decision documents of Health Insurance Review and Assessment and subsequent publications made available following reimbursement decision from ClinicalTrials.Gov and PubMed databases. Changes in the clinical benefit scores were assessed using the American Society of Clinical Oncology Value Framework (ASCO-VF) and the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). A paired t test was performed to test whether there was a difference in the scores between primary and subsequent publications. RESULTS: Of 73 anticancer product/indication pairs, 45 (61.6%) had subsequent publications, of which 62.5% were released within 1 year of reimbursement decision. The mean ESMO-MCBS and ASCO-VF Net Health Benefit scores increased from primary to subsequent publications, although the differences were not significant. The mean ASCO-VF bonus score significantly increased from 15.91 to 19.09 (p = 0.05). The ESMO-MCBS and bonus scores increased by 0.25 and 0.21, respectively, and the bonus score had a greater impact on the ESMO-MCBS score than the preliminary score did. CONCLUSION: The value of drugs demonstrated in subsequent publications varies considerably among oncology drugs, depending on uncertainty associated with the initial evidence and the availability of updated evidence. As decision-making in the face of uncertainty becomes more prevalent, the value frameworks can serve as simple screening tools for re-evaluation in these cases.

Price Reduction of Anticancer Drugs from 2007 to 2019 in South Korea: The Impact of Pharmaceutical Cost-Containment Policies.

OBJECTIVES: To assess price reductions of anticancer drugs in South Korea over 12 years and analyze the association between price reduction, drug characteristics, and repricing mechanisms. METHODS: We constructed a dataset based on the Health Insurance Review and Assessment Service (HIRA) price log of anticancer drugs from January 2007 to June 2019. We investigated each mechanism that resulted in a price reduction, including actual transaction price (ATP), voluntary reduction by a manufacturer, price-volume agreement, expansion of indication or reimbursement scope, price cut at generic entry, lump price cut in April 2012, and re-evaluation. The price reduction rate per year was estimated by dividing the total number of price reduction events by the total period for which the products were on the market. A Poisson regression model was used to estimate the characteristics-adjusted incidence rate ratio of the price reduction. Price reduction per event was also determined across originator and generic products. Data analysis was performed using R (version 3.5.1). RESULTS: Five hundred price reductions occurred in 439 new anticancer drugs, with a reduction rate per 100 product-years of 23. ATP was the most frequent cause (39.2%) but had minimal impact (average reduction per event of 3%), followed by lump price cut (19.2%) and voluntary reduction (10.2%). Generic entries and lump price cut had the greatest impact (16-29% reduction per event). ATP was the most frequently occurring mechanism, followed by generic entry, voluntary reduction, and the lump price-cut in April 2012. CONCLUSIONS: The incidence of price reduction of anticancer drugs increased gradually due to various repricing mechanisms. Although these mechanisms are effective, improvements can be made. Well-designed mechanisms that actively regulate price adjustment are needed to establish repricing policies that adequately reflect changes in the value of drugs over their entire life cycle.

Effects of 17ß-estradiol on the release of monocyte chemotactic protein-1 and MAPK activity in monocytes stimulated with peritoneal fluid from endometriosis patients.

AIM: Hormones and inflammation have been implicated in the pathological process of endometriosis; therefore, we investigated the combined effects of 17ß-estradiol (E2) and peritoneal fluid obtained from patients with endometriosis (ePF) or a control peritoneal fluid (cPF) obtained from patients without endometriosis on the release of monocyte chemotactic protein-1 (MCP-1) by monocytes and the role of signaling pathways. METHODS: Monocytes were cultured with ePF and cPF in the presence of E2; the MCP-1 levels in the supernatants were then measured by ELISA. In addition, mitogen activated protein kinase (MAPK) activation was measured by Western blotting of phosphorylated proteins. RESULTS: E2 down-regulated MCP-1 release by lipopolysaccharide- or cPF-treated monocytes, but failed to suppress its release by ePF-treated monocytes. The release of MCP-1 by ePF- and cPF-treated monocytes was efficiently abrogated by p38 mitogen activated protein kinase (MAPK) inhibitors; however, the MCP-1 release by cPF-treated monocytes, but not by ePF-treated monocytes, was blocked by a MAPK kinase inhibitor. In addition, ePF and cPF induced the phosphorylation of extracellular stress regulated kinase (ERK)1/2, p38 MAPK and c-Jun N-terminal kinase (JNK). E2 decreased the phosphorylation of p38 MAPK, but not ERK1/2 in ePF-treated monocytes; however, E2 decreased the phosphorylation of p38 MAPK, ERK1/2 and JNK in cPF-treated monocytes. CONCLUSIONS: The ability of E2 to modulate MCP-1 production is impaired in ePF-treated monocytes, which may be related to regulation of MAPK activity. These findings suggest that the failure of E2 to suppress ePF-treated production of MCP-1 may be involved in the pathogenesis of endometriosis.

Wettability of denture relining materials under water storage over time

STATEMENT OF PROBLEM: Poor wettability of denture relining materials may lead to retention problems and patient discomfort. PURPOSE: Purpose of this study is to compare and evaluate wettability of nine denture relining materials using contact angle measurements under air and water storage over time. MATERIAL AND METHODS: Nine denture relining materials were investigated in this study. Two heat-curing polymethyl-methacrylate (PMMA) denture base materials: Vertex RS, Lang, one self-curing polyethyl-methacrylate (PEMA) chairside reline resin: Rebase II, six silicone relining materials: Mucopren soft, Mucosoft, Mollosil(R) plus, Sofreliner Touch, GC Reline(TM) Ultrasoft, Silagum automix comfort were used in this experiment. Contact angles were measured using high-resolution drop shape analysis system (DSA 10-MK2, KRUESS, Germany) under three conditions (in air after setting, 1 hour water storage, and 24 hours water storage). Nine materials were classified into three groups according to material composition (Group 1: PMMA, Group 2: PEMA, Group 3: Silicone). Mean values of contact angles were compared using independent samples t-test and one-way ANOVA, followed by a Scheffe's post hoc analysis (alpha= 0.01). RESULTS: Contact angles of materials tested after air and water storage increased in the following order: Group 1 (PMMA), Group 2 (PEMA), Group 3 (Silicone). Heat-cured acrylic denture base resins had more wettability than silicone relining materials. Lang had the highest wettability after 24 hours of water storage. Silicone relining materials had lower wettability due to their hydrophobicity. Wettability of all denture relining materials, except Rebase II and Mollosil(R) plus, increased after 24 hours of water storage. CONCLUSIONS: Conventional heat-cured resin showed the highest wettability, therefore, it can be suggested that heat-cured acrylic resin is material of choice for denture relining materials.