Cost-effectiveness of direct-acting antiviral regimen ombitasvir/paritaprevir/ritonavir in treatment-naïve and treatment-experienced patients infected with chronic hepatitis C virus genotype 1b in Japan

Objective: This study compared the cost-effectiveness of chronic hepatitis C virus (HCV) genotype 1b (GT1b) therapy ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) vs daclatasvir?+?asunaprevir (DCV/ASV) and no treatment in patients without cirrhosis. Cost-effectiveness analyses (CEAs) that compared OBV/PTV/r against DCV/ASV and sofosbuvir/ledipasvir (SOF/LDV) in Y93H mutation-negative, GT1b patients with and without cirrhosis were also included.

Methods: A health state transition model was developed to capture the natural history of HCV. A CEA over a lifetime horizon was performed from the perspective of the public healthcare payer in Japan. Costs, health utilities, and rates of disease progression were derived from published studies. Sustained virologic response (SVR) rates of OBV/PTV/r and DCV/ASV were extracted from Japanese clinical trials. Analyses were performed for treatment-naïve and -experienced patients. Alternative scenarios and input parameter uncertainty on the results were tested.

Results: OBV/PTV/r exhibited superior clinical outcomes vs comparators. For OBV/PTV/r, DCV/ASV, and no treatment, the lifetime risk of decompensated cirrhosis in treatment-naïve patients without cirrhosis was 0.4%, 1.4%, and 9.2%, and hepatocellular carcinoma was 6.5%, 11.4%, and 49.9%, respectively. Quality-adjusted life years (QALYs) were higher in treatment-naïve and -experienced patients without cirrhosis treated with OBV/PTV/r (16.41 and 16.22) vs DCV/ASV (15.83 and 15.66) or no treatment (11.34 and 11.23). In treatment-naïve and -experienced patients without cirrhosis, the incremental cost-effectiveness ratios (ICERs) of OBV/PTV/r vs DCV/ASV were JPY 1,684,751/QALY and JPY 1,836,596/QALY, respectively; OBV/PTV/r was dominant compared with no treatment. In scenario analysis, including GT1b patients with and without cirrhosis who were Y93H mutation-negative, the ICER of OBV/PTV/r vs DCV/ASV was below the Japanese willingness-to-pay threshold of JPY 5 million/QALY, while the ICER of SOF/LDV vs OBV/PTV/r was above this threshold; thus, OBV/PTV/r was cost-effective.

Conclusion: OBV/PTV/r appears to be a cost-effective treatment for chronic HCV GT1b infection against DCV/ASV. OBV/PTV/r dominates no treatment in patients without cirrhosis.     

The bidder exclusion effect

We introduce a new, simple‐to‐compute test of independence of valuations and the number of bidders for ascending button auctions with symmetric, conditionally independent private values. The test involves estimating the expected revenue drop from excluding a bidder at random, which can be computed as a scaled sample average of a difference of order statistics. This object also provides a bound on counterfactual revenue changes from optimal reserve pricing or bidder mergers. We illustrate the approach using data from timber auctions, where we find some evidence that bidder valuations and the number of participants are not independent.     

Managing the right tension

Of all the competing objectives every company faces, three pairs stand out: profitability versus growth, the short term versus the long term, and the whole organization versus the units. In each case, progress on one front usually comes at the expense of progress on the other. The authors researched the performance of more than 1000 companies worldwide over the past two decades and found that most struggle to succeed across the three tensions. From 1983 to 2003, for example, only 32% of these companies more often than not achieved positive profitability and revenue growth at the same time. The problem, the authors discovered, is not so much that managers don't recognize the tensions--those are all too familiar to anyone who has ever run a business. Rather, it is that managers frequently don't focus on the tension that matters most to their company. Even when they do identify the right tension, they usually make the mistake of prioritizing a "lead" objective within it-for example, profitability over growth. As a result, companies often end up moving first in this direction, then in that, and then back again, never quite resolving the tension. The companies that performed best adopted a very different approach. Instead of setting a lead objective, they looked at how best to strengthen what the two sides of each tension have in common: For profitability and growth,the common bond is customer benefit; for the short term and the long, it is sustainable earnings; and for the whole and its parts, it is particular organizational resources and capabilities. The authors describe how companies can select the right tension, what traps they may fall into when they focus on one side over the other, and how to escape these traps by managing to the bonds between objectives.     

An Updated Literature Review of Distance Correlation and Its Applications to Time Series

The concept of distance covariance/correlation was introduced recently to characterise dependence among vectors of random variables. We review some statistical aspects of distance covariance/correlation function, and we demonstrate its applicability to time series analysis. We will see that the auto‐distance covariance/correlation function is able to identify non‐linear relationships and can be employed for testing the i.i.d. hypothesis. Comparisons with other measures of dependence are included.     

Was It Something I Ate? Implementation of the FDA Seafood HACCP Program

We develop a theoretical model of enforcement and compliance under HACCP regulation and use the FDA's seafood inspection records to examine: (1) if the FDA has targeted its inspections under HACCP regulation; (2) the effects of inspections on compliance with HACCP and plant sanitation standards; and (3) the relationship between compliance with HACCP and preexisting sanitation standards. There is some evidence of targeting based on product risk, but not on past compliance performance. The threat of an inspection increases the likelihood of compliance, but only for sanitation inspections, not for HACCP. HACCP compliance does not improve compliance with sanitation standards.     

Ecosophy and tourism: Rethinking a mountain resort

This paper explores how an ecosophically inspired tourism strategy could enhance a Scottish mountain recreational site threatened by climate change. Drawing on qualitative data, the paper focuses on three research questions concerning: the impact of current infrastructure and management strategies on tourist experiences; tourists’ current interpretations and desires; and how the notion of an ecosophically informed tourist attraction might be realised in the light of these experiences, interpretations and desires. Conclusions indicate that the site is a long way from being an ecosophically inspired tourism resort which might foster an engagement with nature. Insights are provided as to how this might be achieved. Critical to the paper is a consideration of how the ‘packaging’ of tourist experiences militates against a meaningful personal connection with the mountain environment.     

Limits to effective leadership style and tactics in critical incident interventions

Leadership effectiveness takes many forms. Its impact on performance can be critical, but by no means does it stand alone, and hence cannot truly be evaluated in isolation. Nor can it be assumed that more of any one effective style is necessarily a good thing. In project management contexts, these issues are particularly salient. Here we study the impact of multiple leadership styles on project performance, as well as the joint role that intervention tactics in general play. Our empirical study demonstrates the benefit of moderate mixes of leadership style and the declining returns on active interventions in these settings.     

Singular mixture copulas

We present a new family of copulas??the Singular Mixture Copulas. We begin with constructing singular copulas whose supports lie on the graphs of two given quantile functions. These copulas are then mixed with respect to a continuous distribution resulting in a nonsingular parametric copula. The Singular Mixture Copulas we construct have a Lebesgue density and a closed form representation. Moreover, they have positive lower and upper tail dependence. As an application we fit the copulas to flood level data. As the results show Singular Mixture Copulas provide an alternative to elliptical copulas, e.g., Gaussian and t-copulas, in modeling strongly dependent random variables.