Likelihood approach for evaluating bioequivalence of highly variable drugs

Bioequivalence (BE) is required for approving a generic drug. The two one‐sided tests procedure (TOST, or the 90% confidence interval approach) has been used as the mainstream methodology to test average BE (ABE) on pharmacokinetic parameters such as the area under the blood concentration‐time curve and the peak concentration. However, for highly variable drugs (%CV > 30%), it is difficult to demonstrate ABE in a standard cross‐over study with the typical number of subjects using the TOST because of lack of power. Recently, the US Food and Drug Administration and the European Medicines Agency recommended similar but not identical reference‐scaled average BE (RSABE) approaches to address this issue. Although the power is improved, the new approaches may not guarantee a high level of confidence for the true difference between two drugs at the ABE boundaries. It is also difficult for these approaches to address the issues of population BE (PBE) and individual BE (IBE). We advocate the use of a likelihood approach for representing and interpreting BE data as evidence. Using example data from a full replicate 2 × 4 cross‐over study, we demonstrate how to present evidence using the profile likelihoods for the mean difference and standard deviation ratios of the two drugs for the pharmacokinetic parameters. With this approach, we present evidence for PBE and IBE as well as ABE within a unified framework. Our simulations show that the operating characteristics of the proposed likelihood approach are comparable with the RSABE approaches when the same criteria are applied. Copyright © 2014 John Wiley & Sons, Ltd.     

What Affects the Happiness of Adopted Children in South Korea? Does the Adoption Matter to Their Happiness?

Child and Adolescent Social Work Journal - Since the ultimate goal of adoption is to provide children a happy life in a stable family environment, our major concern is children’s happiness...     

Static Numbers to Dynamic Statistics: Designing a Policy-Friendly Social Policy Indicator Framework

In line with the economic crisis and rapid socio-demographic changes, the interest in ??social?? and ??well-being?? indicators has been revived. Social indicator movements of the 1960s resulted in the establishment of social indicator statistical frameworks; that legacy has remained intact in many national governments and international organisations. With this background, this research examines whether existing social indicator frameworks are valid and effective enough to address increasingly complex social issues. The authors argue that, despite some improvements, current social indicators fail to provide an effective framework and tool for measuring the progress of social welfare and also for developing or reforming social policy to cope with newly emerging social problems. While proposing a new social indicator framework based on the Organisation for Economic Co-operation and Development??s pressure-state-response (PSR) model, the paper argues that the new framework should be more than displaying static numbers but should use dynamic statistics revealing causes and effects and shedding light on social and policy changes.     

Alternative posterior consistency results in nonparametric binary regression using Gaussian process priors

We establish consistency of posterior distribution when a Gaussian process prior is used as a prior distribution for the unknown binary regression function. Specifically, we take the work of Ghosal and Roy [2006. Posterior consistency of Gaussian process prior for nonparametric binary regression. Ann. Statist. 34, 2413–2429] as our starting point, and then weaken their assumptions on the smoothness of the Gaussian process kernel while retaining a stronger yet applicable condition about design points. Furthermore, we extend their results to multi-dimensional covariates under a weaker smoothness condition on the Gaussian process. Finally, we study the extent to which posterior consistency can be achieved under a general model where, when additional hyperparameters in the covariance function of a Gaussian process are involved.     

Applicability of the Social Development Model to Urban Ethnic Minority Youth: Examining the Relationship between External Constraints,Family Socialization,and Problem Behaviors

The development of preventive interventions targeting adolescent problem behaviors requires a thorough understanding of risk and protective factors for such behaviors. However, few studies examine whether different cultural and ethnic groups share these factors. This study is an attempt to fill a gap in research by examining similarities and differences in risk factors across racial and ethnic groups. The social development model has shown promise in organizing predictors of problem behaviors. This article investigates whether a version of that model can be generalized to youth in different racial and ethnic groups (N=2,055, age range from 11 to 15), including African American (n=478), Asian Pacific Islander (API) American (n=491), multiracial (n=442), and European American (n=644) youth. The results demonstrate that common risk factors can be applied to adolescents, regardless of their race and ethnicity. The findings also demonstrate that there are racial and ethnic differences in the magnitudes of relationships among factors that affect problem behaviors. Further study is warranted to develop a better understanding of these differential magnitudes.     

Accelerated life regression modelling of dependent bivariate time‐to‐event data

To analyze bivariate time‐to‐event data from matched or naturally paired study designs, researchers frequently use a random effect called frailty to model the dependence between within‐pair response measurements. The authors propose a computational framework for fitting dependent bivariate time‐to‐event data that combines frailty distributions and accelerated life regression models. In this framework users can choose from several parametric options for frailties, as well as the conditional distributions for within‐pair responses. The authors illustrate the flexibility that their framework represents using paired data from a study of laser photocoagulation therapy for retinopathy in diabetic patients.     

Interest rate policies and inflation in interdependent economies: Recent policy dilemmas

This paper examines Federal Reserve Board policies that are premised on a negative short-run association of interest rate movements and the rate of inflation. In particular, econometric evidence is provided, supporting the view that tighter monetary policy appears to raise inflation rates in the short run. Conversely, it is demonstrated that easier monetary policy does not necessarily raise inflation rates in the short run. In the case of uncoordinated monetary restrictiveness, interest rate competition among major countries can produce higher inflation and lower growth than was originally intended.     

Distribution system choice in a service industry: An analysis of international insurance firms operating in the United States

Service firms play an increasingly important role in the global economy. However, the internationalization strategies of such firms, and especially their distribution system choices, have been underexplored in the international management literature. One specific service industry that has internationalized rapidly in recent years is the insurance industry. This paper examines the determinants and performance implications of the choice by international insurance firms between two rival distribution systems: direct writing and independent sales agents. Drawing on the transaction cost theory-based literature on resource commitment, control, and risk, we develop hypotheses on the determinants of the choice between these two distribution systems and on the performance implications of this choice for insurance firms. Analyzing a sample of 168 distribution entries into the United States by insurance firms from six foreign countries over the 1992–2000 period, we find that cultural distance has a U-shaped effect on the probability of direct writing, and that an insurer's intangible assets have a positive effect on this probability. We also find that the direct writing system performs better in terms of profitability, but that the independent agency system performs better in terms of market share growth.     

Analyzing Evacuation Versus Shelter‐in‐Place Strategies After a Terrorist Nuclear Detonation

We superimpose a radiation fallout model onto a traffic flow model to assess the evacuation versus shelter‐in‐place decisions after the daytime ground‐level detonation of a 10‐kt improvised nuclear device in Washington, DC. In our model, ≈80k people are killed by the prompt effects of blast, burn, and radiation. Of the ≈360k survivors without access to a vehicle, 42.6k would die if they immediately self‐evacuated on foot. Sheltering above ground would save several thousand of these lives and sheltering in a basement (or near the middle of a large building) would save of them. Among survivors of the prompt effects with access to a vehicle, the number of deaths depends on the fraction of people who shelter in a basement rather than self‐evacuate in their vehicle: 23.1k people die if 90% shelter in a basement and 54.6k die if 10% shelter. Sheltering above ground saves approximately half as many lives as sheltering in a basement. The details related to delayed (i.e., organized) evacuation, search and rescue, decontamination, and situational awareness (via, e.g., telecommunications) have very little impact on the number of casualties. Although antibiotics and transfusion support have the potential to save ≈10k lives (and the number of lives saved from medical care increases with the fraction of people who shelter in basements), the logistical challenge appears to be well beyond current response capabilities. Taken together, our results suggest that the government should initiate an aggressive outreach program to educate citizens and the private sector about the importance of sheltering in place in a basement for at least 12 hours after a terrorist nuclear detonation.