Pricing in the Market for Anticancer Drugs

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

Spatially valid proprioceptive cues improve the detection of a visual stimulus

Vision and proprioception are the main sensory modalities that convey hand location and direction of movement. Fusion of these sensory signals into a single robust percept is now well documented. However, it is not known whether these modalities also interact in the spatial allocation of attention, which has been demonstrated for other modality pairings. The aim of this study was to test whether proprioceptive signals can spatially cue a visual target to improve its detection. Participants were instructed to use a planar manipulandum in a forward reaching action and determine during this movement whether a near-threshold visual target appeared at either of two lateral positions. The target presentation was followed by a masking stimulus, which made its possible location unambiguous, but not its presence. Proprioceptive cues were given by applying a brief lateral force to the participant’s arm, either in the same direction (validly cued) or in the opposite direction (invalidly cued) to the on-screen location of the mask. The d′ detection rate of the target increased when the direction of proprioceptive stimulus was compatible with the location of the visual target compared to when it was incompatible. These results suggest that proprioception influences the allocation of attention in visual spac

Adaptive tuning functions arise from visual observation of past movement

Visual observation of movement plays a key role in action. For example, tennis players have little time to react to the ball, but still need to prepare the appropriate stroke. Therefore, it might be useful to use visual information about the ball trajectory to recall a specific motor memory. Past visual observation of movement (as well as passive and active arm movement) affects the learning and recall of motor memories. Moreover, when passive or active, these past contextual movements exhibit generalization (or tuning) across movement directions. Here we extend this work, examining whether visual motion also exhibits similar generalization across movement directions and whether such generalization functions can explain patterns of interference. Both the adaptation movement and contextual movement exhibited generalization beyond the training direction, with the visual contextual motion exhibiting much broader tuning. A second experiment demonstrated that this pattern was consistent with the results of an interference experiment where opposing force fields were associated with two separate visual movements. Overall, our study shows that visual contextual motion exhibits much broader (and shallower) tuning functions than previously seen for either passive or active movements, demonstrating that the tuning characteristics of past motion are highly dependent on their sensory modality

Learning near-optimal policies with Bellman-residual minimization based fitted policy iteration and a single sample path

We consider the problem of finding a near-optimal policy in continuous space, discounted Markovian Decision Problems given the trajectory of some behaviour policy. We study the policy iteration algorithm where in successive iterations the action-value functions of the intermediate policies are obtained by picking a function from some fixed function set (chosen by the user) that minimizes an unbiased finite-sample approximation to a novel loss function that upper-bounds the unmodified Bellman-residual criterion. The main result is a finite-sample, high-probability bound on the performance of the resulting policy that depends on the mixing rate of the trajectory, the capacity of the function set as measured by a novel capacity concept that we call the VC-crossing dimension, the approximation power of the function set and the discounted-average concentrability of the future-state distribution. To the best of our knowledge this is the first theoretical reinforcement learning result for off-policy control learning over continuous state-spaces using a single trajectory

The predictive validity of a Brain Care Score for dementia and stroke: data from the UK Biobank cohort

Introduction: The 21-point Brain Care Score (BCS) was developed through a modified Delphi process in partnership with practitioners and patients to promote behavior changes and lifestyle choices in order to sustainably reduce the risk of dementia and stroke. We aimed to assess the associations of the BCS with risk of incident dementia and stroke. Methods: The BCS was derived from the United Kingdom Biobank (UKB) baseline evaluation for participants aged 40–69 years, recruited between 2006–2010. Associations of BCS and risk of subsequent incident dementia and stroke were estimated using Cox proportional hazard regressions, adjusted for sex assigned at birth and stratified by age groups at baseline. Results: The BCS (median: 12; IQR:11–14) was derived for 398,990 UKB participants (mean age: 57; females: 54%). There were 5,354 incident cases of dementia and 7,259 incident cases of stroke recorded during a median follow-up of 12.5 years. A five-point higher BCS at baseline was associated with a 59% (95%CI: 40-72%) lower risk of dementia among participants aged 59 years. A five-point higher BCS was associated with a 48% (95%CI: 39-56%) lower risk of stroke among participants aged 59. Discussion: The BCS has clinically relevant and statistically significant associations with risk of dementia and stroke in approximately 0.4 million UK people. Future research includes investigating the feasibility, adaptability and implementation of the BCS for patients and providers worldwide

Health care use and costs of adverse drug events emerging from outpatient treatment in Germany: A modelling approach

<p>Abstract</p> <p>Background</p> <p>This study's aim was to develop a first quantification of the frequency and costs of adverse drug events (ADEs) originating in ambulatory medical practice in Germany.</p> <p>Methods</p> <p>The frequencies and costs of ADEs were quantified for a base case, building on an existing cost-of-illness model for ADEs. The model originates from the U.S. health care system, its structure of treatment probabilities linked to ADEs was transferred to Germany. Sensitivity analyses based on values determined from a literature review were used to test the postulated results.</p> <p>Results</p> <p>For Germany, the base case postulated that about 2 million adults ingesting medications have will have an ADE in 2007. Health care costs related to ADEs in this base case totalled 816 million Euros, mean costs per case were 381 Euros. About 58% of costs resulted from hospitalisations, 11% from emergency department visits and 21% from long-term care. Base case estimates of frequency and costs of ADEs were lower than all estimates of the sensitivity analyses.</p> <p>Discussion</p> <p>The postulated frequency and costs of ADEs illustrate the possible size of the health problems and economic burden related to ADEs in Germany. The validity of the U.S. treatment structure used remains to be determined for Germany. The sensitivity analysis used assumptions from different studies and thus further quantified the information gap in Germany regarding ADEs.</p> <p>Conclusions</p> <p>This study found costs of ADEs in the ambulatory setting in Germany to be significant. Due to data scarcity, results are only a rough indication.</p

The Fifth Data Release of the Sloan Digital Sky Survey

This paper describes the Fifth Data Release (DR5) of the Sloan Digital Sky Survey (SDSS). DR5 includes all survey quality data taken through June 2005 and represents the completion of the SDSS-I project (whose successor, SDSS-II will continue through mid-2008). It includes five-band photometric data for 217 million objects selected over 8000 square degrees, and 1,048,960 spectra of galaxies, quasars, and stars selected from 5713 square degrees of that imaging data. These numbers represent a roughly 20% increment over those of the Fourth Data Release; all the data from previous data releases are included in the present release. In addition to "standard" SDSS observations, DR5 includes repeat scans of the southern equatorial stripe, imaging scans across M31 and the core of the Perseus cluster of galaxies, and the first spectroscopic data from SEGUE, a survey to explore the kinematics and chemical evolution of the Galaxy. The catalog database incorporates several new features, including photometric redshifts of galaxies, tables of matched objects in overlap regions of the imaging survey, and tools that allow precise computations of survey geometry for statistical investigations.Comment: ApJ Supp, in press, October 2007. This paper describes DR5. The SDSS Sixth Data Release (DR6) is now public, available from http://www.sdss.or

An assessment of the impact of herb-drug combinations used by cancer patients

Background Herb/Dietary Supplements (HDS) are the most popular Complementary and Alternative Medicine (CAM) modality used by cancer patients and the only type which involves the ingestion of substances which may interfere with the efficacy and safety of conventional medicines. This study aimed to assess the level of use of HDS in cancer patients undergoing treatment in the UK, and their perceptions of their effects, using 127 case histories of patients who were taking HDS. Previous studies have evaluated the risks of interactions between HDS and conventional drugs on the basis on numbers of patient using HDSs, so our study aimed to further this exploration by examining the actual drug combinations taken by individual patients and their potential safety. Method Three hundred seventy-five cancer patients attending oncology departments and centres of palliative care at the Oxford University Hospitals Trust (OUH), Duchess of Kent House, Sobell House, and Nettlebed Hospice participated in a self-administered questionnaire survey about their HDS use with their prescribed medicines. The classification system of Stockley’s Herbal Medicine’s Interactions was adopted to assess the potential risk of herb-drug interactions for these patients. Results 127/375 (34 %; 95 % CI 29, 39) consumed HDS, amounting to 101 different products. Most combinations were assessed as ‘no interaction’, 22 combinations were categorised as ‘doubt about outcomes of use’, 6 combinations as ‘Potentially hazardous outcome’, one combination as an interaction with ‘Significant hazard’, and one combination as an interaction of “Life-threatening outcome”. Most patients did not report any adverse events. Conclusion Most of the patients sampled were not exposed to any significant risk of harm from interactions with conventional medicines, but it is not possible as yet to conclude that risks in general are over-estimated. The incidence of HDS use was also less than anticipated, and significantly less than reported in other areas, illustrating the problems when extrapolating results from one region (the UK), in one setting (NHS oncology) in where patterns of supplement use may be very different to those elsewhere