Cost-effectiveness of elagolix versus leuprolide acetate for treating moderate-to-severe endometriosis pain in the USA.

AIM: To assess the cost-effectiveness of elagolix versus leuprolide acetate in women with moderate to severe endometriosis pain. METHODS: A Markov model was developed. The efficacy of leuprolide acetate was derived from statistical prediction models using elagolix trial data. Model inputs were extracted from Phase III clinical trials and published literature. RESULTS: Compared with leuprolide acetate, elagolix generated positive net monetary benefit (NMB) assuming a payer's willingness-to-pay threshold of US$100,000 per quality-adjusted life year over a 1-year time horizon: US$5660 for elagolix 150 mg and US$6443 for elagolix 200 mg. The 2-year NMBs were also positive. CONCLUSION: Elagolix was cost effective versus leuprolide acetate in the management of moderate to severe endometriosis pain over 1- and 2-year time horizons. Results were robust in sensitivity analyses.

Elagolix for endometriosis: all that glitters is not gold.

Elagolix, an orally active non-peptidic GnRH antagonist, has been approved by the Food and Drug Administration for the management of moderate to severe pain associated with endometriosis. As the degree of ovarian suppression obtained with elagolix is dose-dependent, pain relief may be achieved by modulating the level of hypo-oestrogenism while limiting side effects. Elagolix may thus be considered a novelty in terms of its endocrine and pharmacological properties but not for its impact on the pathogenic mechanisms of endometriosis, as the target of this new drug is, yet again, alteration of the hormonal milieu. Given the oestrogen-dependent nature of endometriosis, a reduction of side effects may imply a proportionate decrease in pain relief. Furthermore, if low elagolix doses are used, ovulation is not consistently inhibited, and patients should use non-hormonal contraceptive systems and perform serial urine pregnancy tests to rule out unplanned conception during periods of treatment-induced amenorrhoea. If high elagolix doses are used to control severe pain for long periods of time, add-back therapies should be added, similar to that prescribed when using GnRH agonists. To date, the efficacy of elagolix has only been demonstrated in placebo-controlled explanatory trials. Pragmatic trials comparing elagolix with low-dose hormonal contraceptives and progestogens should be planned to verify the magnitude of the incremental benefit, if any, of this GnRH antagonist over currently used standard treatments. The price of elagolix may impact on patient adherence and, hence, on clinical effectiveness. In the USA, the manufacturer AbbVie Inc. priced elagolix (OrilissaTM) at around $10 000 a year, i.e. $845 per month. When faced with unaffordable treatments, some patients may choose to forego care. If national healthcare systems are funded by the tax payer, the approval and the use of a new costly drug to treat a chronic condition, such as endometriosis, means that some finite financial resources will be diverted from other areas, or that similar patients will not receive the same level of care. Thus, defining the overall 'value' of a new drug for endometriosis also has ethical implications, and trade-offs between health outcomes and costs should be carefully weighed up.

Non-stick science: Sixty years of research and (in)action on fluorinated compounds.

Understandings of environmental governance both assume and challenge the relationship between expert knowledge and corresponding action. We explore this interplay by examining the context of knowledge production pertaining to a contested class of chemicals. Per-and polyfluorinated alkyl substances (PFASs) are widely used industrial compounds containing chemical chains of carbon and fluorine that are persistent, bioaccumulative and toxic. Although industry and regulatory scientists have studied the exposure and toxicity concerns of these compounds for decades, and several contaminated communities have documented health concerns as a result of their high levels of exposure, PFAS use remains ubiquitous in a large range of consumer and industrial products. Despite this significant history of industry knowledge production documenting exposure and toxicity concerns, the regulatory approach to PFASs has been limited. This is largely due to a regulatory framework that privileges industry incentives for rapid market entry and trade secret protection over substantive public health protection, creating areas of unseen science, research that is conducted but never shared outside of institutional boundaries. In particular, the risks of PFASs have been both structurally hidden and unexamined by existing regulatory and industry practice. This reveals the uneven pathways that construct issues of social and scientific concern.

A scalable and regioselective synthesis of 2-difluoromethyl pyridines from commodity chemicals.

A scalable de novo synthesis of difluoromethyl pyridines from inexpensive materials is reported. The pyridyl subunit is built around the difluoromethyl group rather than a late stage introduction of this moiety. This user-friendly approach allows access to a diverse range of substitution patterns on all positions on the ring system and on the difluoromethyl group.

A pilot survey of legacy and current commercial fluorinated chemicals in human sera from United States donors in 2009.

Human biomonitoring has traditionally focused on analyzing the perfluorocarboxylates (PFCAs) and perfluorosulfonates (PFSAs), although the presence of other unidentified fluorinated chemicals has been demonstrated through total organofluorine analysis. Exposure to legacy and current commercial fluorinated chemicals was investigated by analyzing fifty human sera samples collected in 2009 from the United States for forty fluorinated analytes that included the polyfluoroalkyl phosphate diesters (diPAPs), N-ethyl perfluorooctanesulfonamidoethanol-based polyfluoroalkyl phosphate diester (SAmPAP), one fluorotelomer mercaptoalkyl phosphate diester congener (FTMAP), fluorotelomer sulfonates (FTSs), perfluorophosphonates (PFPAs), and perfluorophosphinates (PFPiAs). DiPAP concentrations (0.035-0.136 µg/L) for the more dominant congeners (6:2, 6:2/8:2, 8:2) were lower than those reported in human sera samples collected in 2004, 2005, and 2008. The SAmPAP and 6:2 FTMAP were not detected, but exposure to SAmPAP was suggested based on the detection of one of its potential degradation intermediates, N-ethyl perfluorooctanesulfonamidoacetate (N-EtFOSAA). PFPiAs were detected for the first time in human sera, with C6/C6 and C6/C8 PFPiAs as the dominant congeners, observed in >50% of the samples.

Hydrofluoroalkane-134a beclomethasone as a dominant economic asthma therapy.

Inhaled corticosteroids for asthma treatment have become mainstay of therapy for patients with persistent asthma. Numerous inhaled corticosteroids are available but to date no prospective cost-effectiveness studies have been reported using exclusively US patients and costs. The purpose of this study was to examine the cost-effectiveness of HFA-bectomethasone (QVAR) compared to CFC-beclomethasone (Vanceril) using data from a year-long prospective randomized, open label, parallel multicenter trial. Eligibility criteria required patients to have been on a stable dose of CFC-BDP prior to enrollment. Patients were randomized to either HFA-BDP at approximately half their previous daily dose of CFC-BDP or to continue CFC-BDP Effectiveness data, in terms of symptom-free days (SFDs), were used in a cost-effectiveness analysis conducted from the viewpoint of managed care. Patients receiving HFA-BDP reported a greater increase (median = 22.1) in the number of SFDs than those receiving CFC-BDP (median = 14.3) (P = 0.03). Total costs of care were less for patients taking HFA-BDP (median = dollars 668) compared to CFC-BDP (median = dollars 977). The median incremental cost-effectiveness ratio was dollars -5.77 (95% CI: dollars -68.08 to dollars -4.08). The results of this analysis indicate that HFA-BDP was a dominant therapy (more effective, less costly) compared to CFC-BDP.

Halogenated compounds and climate change: future emission levels and reduction costs.

OBJECTIVES: This work assesses the contribution to climate change resulting from emissions of the group of halogenated greenhouse gases. METHODS: A bottom-up emission model covering 22 technological sectors in four major regions is described. Emission estimates for 1996 and projection for 2010 and 2020 are presented. The costs for deep cuts into projected emission levels are calculated. RESULTS: The substances covered by this study have contributed emissions of 1100 +/- 800 MT CO2 equivalents per year in 1996. In terms of their relative contribution to emissions of CO2 equivalents, this corresponds to 3 +/- 2% of global emissions of all anthropogenic greenhouse gases. The wide range of uncertainty is due to the poorly quantified net global warming potential of the ozone depleting substances, which have an indirect cooling effect on climate through the destruction of stratospheric ozone. For annual emissions of HFCs, PFCs and SF6 (which are regulated under the Kyoto Protocol and for which global warming potentials are well defined), the relative contribution is projected to increase to 2% (600 MT CO2 eq.) of global greenhouse gas emissions by 2010. This trend is expected to continue, emissions are projected to grow to a contribution of roughly 3% (870 MT CO2 eq.) in 2020 compared to 0.9% (300 MT CO2 eq.) in 1996. For HFCs, PFCs and SF6, this study identifies global emission reduction potentials of 260 MT CO2 eq. per year in 2010 and 640 MT CO2 eq. per year in 2020 at below US$ 50 per ton. These values correspond to roughly 40% and 75% of projected emissions in 2010 and 2020, respectively.

Using hydrofluoroether solvents to replace HCFC-141b, Part II.

The use of hydrochlorofluocarbon (HFC) solvents is banned from the end of 2001. Part of this article assessed the merits of using hydrofluoroethers as replacement solvents. Alternatives to HFCs are more expensive. Part II looks at how to reduce the cost of conversion.