Pricing in the Market for Anticancer Drugs Howard, David H.; Bach, Peter B.; Berndt, Ernst R. ...
The Journal of economic perspectives,
2015, Volume:
29, Issue:
1
Journal Article
Peer reviewed
Open access
In 2011, Bristol-Myers Squibb set the price of its newly approved melanoma drug ipilimumab—brand name Yervoy—at $120,000 for a course of therapy. The drug was associated with an incremental increase ...in life expectancy of four months. Drugs like ipilimumab have fueled the perception that the launch prices of new anticancer drugs and other drugs in the so-called “specialty” pharmaceutical market have been increasing over time and that increases are unrelated to the magnitude of the expected health benefits. In this paper, we discuss the unique features of the market for anticancer drugs and assess trends in the launch prices for 58 anticancer drugs approved between 1995 and 2013 in the United States. We restrict attention to anticancer drugs because the use of median survival time as a primary outcome measure provides a common, objective scale for quantifying the incremental benefit of new products. We find that the average launch price of anticancer drugs, adjusted for inflation and health benefits, increased by 10 percent annually—or an average of $8,500 per year—from 1995 to 2013. We argue that the institutional features of the market for anticancer drugs enable manufacturers to set the prices of new products at or slightly above the prices of existing therapies, giving rise to an upward trend in launch prices. Government-mandated price discounts for certain classes of buyers may have also contributed to launch price increases as firms sought to offset the growth in the discount segment by setting higher prices for the remainder of the market.
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BFBNIB, CEKLJ, INZLJ, IZUM, KILJ, NMLJ, NUK, ODKLJ, PILJ, PNG, SAZU, UL, UM, UPUK, ZRSKP
Time-of-flight (TOF) measurement capability promises to improve PET image quality. We characterized the physical and clinical PET performance of the first Biograph mCT TOF PET/CT scanner (Siemens ...Medical Solutions USA, Inc.) in comparison with its predecessor, the Biograph TruePoint TrueV. In particular, we defined the improvements with TOF. The physical performance was evaluated according to the National Electrical Manufacturers Association (NEMA) NU 2-2007 standard with additional measurements to specifically address the TOF capability. Patient data were analyzed to obtain the clinical performance of the scanner. As expected for the same size crystal detectors, a similar spatial resolution was measured on the mCT as on the TruePoint TrueV. The mCT demonstrated modestly higher sensitivity (increase by 19.7 ± 2.8%) and peak noise equivalent count rate (NECR) (increase by 15.5 ± 5.7%) with similar scatter fractions. The energy, time and spatial resolutions for a varying single count rate of up to 55 Mcps resulted in 11.5 ± 0.2% (FWHM), 527.5 ± 4.9 ps (FWHM) and 4.1 ± 0.0 mm (FWHM), respectively. With the addition of TOF, the mCT also produced substantially higher image contrast recovery and signal-to-noise ratios in a clinically-relevant phantom geometry. The benefits of TOF were clearly demonstrated in representative patient images.
In August 2012, the Food and Drug Administration investigated the safety of codeine use by children after tonsillectomy and/or adenoidectomy, culminating in a black box warning in February 2013. The ...objective of this study was to evaluate the association between the investigation and opioid prescribing to children undergoing these surgeries.
We identified 362 992 privately insured children in the 2010-2015 Truven MarketScan Commercial Claims and Encounters database who underwent tonsillectomy and/or adenoidectomy. Using an interrupted time series design, we estimated level and slope changes in the proportion of children with ≥1 prescription fills for codeine and ≥1 fills for an alternative opioid, such as hydrocodone, within 7 days of surgery.
The investigation was associated with a significant -13.3 (95% confidence interval: -14.5 to -12.1) percentage point level change in the proportion of children with ≥1 prescription fills for codeine after tonsillectomy and/or adenoidectomy. Despite this drop, 5.1% of children had ≥1 prescription fills for codeine in December 2015. The investigation was not associated with significant level changes in alternative opioid prescribing, although the proportion of children receiving alternative opioids increased during the study period because of other factors.
The Food and Drug Administration investigation substantially decreased codeine prescribing to children after tonsillectomy and/or adenoidectomy. However, 1 in 20 children undergoing these surgeries were still prescribed codeine in December 2015 despite its well-documented safety and efficacy issues.
A seeded FEL driven by a linac based on super conducting cavities, generating 108-1010 coherent photons per shot at 2-5 keV with 0.2-1 MHz of repetition rate, can address the need of a source devoted ...to fine analysis of matter using the linear spectroscopy technique. The seeding scheme described hereafter is a multi-stage cascade upshifting the radiation frequency by a factor 20-40. The x-ray range can be achieved with a seed constituted by a coherent flash in the extreme ultraviolet range provided by an FEL oscillator operating at 12-14 nm. The whole chain of x-ray generation is described by means of start-to-end three-dimensional simulations.
Summary In an era when the number of expedited and conditional review pathways for newly available brand-name drugs and biosimilar medicines to treat serious and life-threatening diseases is ...increasing, defining pharmacovigilance has never been more crucial. 21st century pharmacovigilance is not merely about uncovering, reporting, and addressing adverse events associated with already approved and marketed agents, but can be described as the systematic monitoring of the process of pre-market review and post-market surveillance, which includes the use of medicines in everyday practice. Pharmacovigilance identifies previously unrecognised adverse events or changes in the patterns of these effects, the quality and adequacy of drug supply, and should ensure effective communication with the public, health-care professionals, and patients about the optimum safety and effective use of medicines. In this paper, the first in a Series of three about drug safety in oncology, we discuss evolving challenges in the purview, roles, and responsibilities of the US Food and Drug Administration and the European Medicines Agency with respect to pharmacovigilance efforts, with a special emphasis on oncology treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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•The serotonin system is believed to be heavily involved in L-DOPA induced dyskinesia (LID).•Dopamine loss and chronic L-DOPA treatment appear to initiate a gain-of-function for the ...serotonin transporter (SERT).•When DAT levels are low, SERT appears to take up extracellular dopamine, which may play a role in LID development and maintenance.
L-DOPA is the standard treatment for Parkinson’s disease (PD), but chronic treatment typically leads to L-DOPA-induced dyskinesia (LID). LID involves a complex interaction between the remaining dopamine (DA) system and the semi-homologous serotonin (5-HT) system. Since serotonin transporters (SERT) have some affinity for DA uptake, they may serve as a functional compensatory mechanism when DA transporters (DAT) are scant. DAT and SERT’s functional contributions in the dyskinetic brain have not been well delineated. The current investigation sought to determine how DA depletion and L-DOPA treatment affect DAT and SERT transcriptional processes, translational processes, and functional DA uptake in the 6-hydroxydopamine-lesioned hemi-parkinsonian rat. Rats were counterbalanced for motor impairment into equally lesioned treatment groups then given daily L-DOPA (0 or 6 mg/kg) for 2 weeks. At the end of treatment, the substantia nigra was processed for tyrosine hydroxylase (TH) and DAT gene expression and dorsal raphe was processed for SERT gene expression. The striatum was processed for synaptosomal DAT and SERT protein expression and ex vivo DA uptake. Nigrostriatal DA loss severely reduced DAT mRNA and protein expression in the striatum with minimal changes in SERT. L-DOPA treatment, while not significantly affecting DAT or SERT alone, did increase striatal SERT:DAT protein ratios. Using ex vivo microdialysis, L-DOPA treatment increased DA uptake via SERT when DAT was depleted. Overall, these results suggest that DA loss and L-DOPA treatment uniquely alter DAT and SERT, revealing implications for monoamine transporters as potential biomarkers and therapeutic targets in the hemi-parkinsonian model and dyskinetic PD patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Passive bistatic radar or passive coherent location is gaining interest in the radar community, as it provides some advantages with respect to active radar. Passive radar does not aim to replace ...active radar; it provides a good complement to it. The computational effort that is required to implement the required signal processing is one of the drawbacks that affect passive radars. In this paper, a suboptimal but computationally affordable detection algorithm is investigated that is applicable to arbitrary waveforms (different types of illuminators of opportunity). First, a detailed mathematical formulation of the proposed suboptimum algorithm is derived. A theoretical performance analysis is then provided based on a comparison of the proposed with the optimum two-dimensional matched filter. Finally, simulated and real data are used to demonstrate the effectiveness of the proposed algorithm and to validate the theoretical performance analysis.
Abstract
Ultra-hot Jupiters with equilibrium temperatures greater than 2000 K are uniquely interesting targets as they provide us crucial insights into how atmospheres behave under extreme ...conditions. This class of giant planets receives intense radiation from their host star and usually has strongly irradiated and highly inflated atmospheres. At such a high temperature, cloud formation is expected to be suppressed and thermal dissociation of water vapor could occur. We observed the ultra-hot Jupiter WASP-76b with seven transits and five eclipses using the Hubble Space Telescope and the Spitzer Space Telescope (Spitzer) for a comprehensive study of its atmospheric chemical and physical processes. We detected TiO and H
2
O absorption in the optical and near-infrared transit spectrum. Additional absorption by a number of neutral and ionized heavy metals like Fe, Ni, Ti, and SiO help explain the short-wavelength transit spectrum. The secondary eclipse spectrum shows muted water feature but a strong CO emission feature in Spitzer’s 4.5
μ
m band indicating an inverted temperature pressure profile. We analyzed both the transit and eclipse spectra with a combination of self-consistent PHOENIX models and atmospheric retrieval. Both spectra were well fitted by the self-consistent PHOENIX forward atmosphere model in chemical and radiative equilibrium at solar metallicity, adding to the growing evidence that both TiO/VO and NUV heavy metals opacity are prominent NUV-optical opacity sources in the stratospheres of ultra-hot Jupiters.
Orphan drug development is crucial for children, who are disproportionately affected by rare diseases. Data are lacking on the number, nature, and benefit of recently approved pediatric orphan ...indications.
We classified the 402 orphan indications the US Food and Drug Administration approved between 2010 and 2018 as "pediatric" if they were approved for children only or targeted pediatric diseases. We determined the number of unique diseases targeted by pediatric orphan indications and calculated the proportion that were for (1) novel drugs, (2) non-novel drugs approved to treat ≥1 common disease, and (3) non-novel drugs approved only to treat rare diseases. Among pediatric orphan indications eligible for US Food and Drug Administration breakthrough designation (granted to drugs potentially representing major therapeutic advances), we calculated the proportion receiving this designation.
Of the 402 orphan indications, 136 (33.8%) were pediatric. These 136 indications targeted 87 unique diseases; 21 diseases were targeted by ≥1 indication. Of the 136 pediatric orphan indications, 60 (44.1%) were for novel drugs, 45 (33.1%) were for non-novel drugs approved to treat ≥1 common disease, and 31 (22.8%) were for non-novel drugs approved only to treat rare diseases. Among 97 indications eligible for breakthrough designation, 20 (20.6%) received this designation.
Recent orphan drug development has increased the availability of treatments for pediatric rare diseases. Most pediatric orphan indications expanded use of existing drugs, and many targeted the same disease. Some indications may represent breakthroughs, but substantial unmet need for treatments remains for most pediatric rare diseases.
Objective: The influence of postprandial blood glucose on diabetes complications is intensively debated. We aimed to evaluate the predictive role of both fasting and postprandial blood glucose on ...cardiovascular events in type 2 diabetes and the influence of gender.
Methods: In a population of 529 (284 men and 245 women) consecutive type 2 diabetic patients attending our diabetes clinic, we evaluated the relationships, corrected for cardiovascular risk factors and type of treatment, between cardiovascular events in a 5-yr follow-up and baseline values of hemoglobin A1c (HbA1c) and blood glucose measured: 1) after an overnight fast, 2) after breakfast, 3) after lunch, and 4) before dinner. Continuous variables were categorized into tertiles.
Results: We recorded cardiovascular events in 77 subjects: 54 of 284 men (19%) and 23 of 245 women (9.4%). Univariate analysis indicated that cardiovascular events were associated with increasing age, longer diabetes duration, and higher HbA1c and fibrinogen in men, and higher systolic blood pressure, albumin excretion rate, HbA1c, and all blood glucose values in women. Smoking was more frequent in subjects with events. When all blood glucose values and HbA1c were introduced simultaneously in the models, only blood glucose after lunch predicted cardiovascular events, with hazard ratio of the third tertile vs. the first and the second tertiles greater in women (5.54; confidence interval, 1.45–21.20) than in men (2.12; confidence interval, 1.04–4.32; P < 0.01).
Conclusions: Postprandial, but not fasting, blood glucose is an independent risk factor for cardiovascular events in type 2 diabetes, with a stronger predictive power in women than in men, suggesting that more attention should be paid to postprandial hyperglycemia, particularly in women.
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