Pharmacovigilance in Clinical Trials: Current Practice and Challenges

In view of the MENA increasing participation in multinational trials and the increasing number of national/regional trials, this article explores potential areas of pharmacovigilance, requiring reform and provides recommendations for building a robust safety reporting system. Regulatory silence on expedited reporting requirements creates confusion for local sites that are part of multinational trials. Not allowing waiver for serious adverse events that are protocol specified or are study endpoints, along with lack of emphasis on causality as reporting criteria, adds substantial burden of uninformative cases for regulatory review. Despite global focus on Development Safety Update Report, local regulators are not yet insistent on real-time update of a drug’s cumulative safety profile. Issues like reporting requirements for generic trials, pregnancy reporting and lenient timeline for death/life-threatening events need attention. Finally, the need to formulate an all-encompassing local pharmacovigilance guideline, in sync with global practice cannot be overemphasized.     

Putting Process (Back) In: Research on the Internationalization Process of the Firm

This paper provides a critique of existing research on the internationalization process of the firm and proposes an agenda for future inquiry. In recent years, process approaches have received increasing attention in management research, leading to a more refined understanding of the distinction between process and variance paradigms. We apply a process lens to a well‐established sub‐field of international business, namely the internationalization process of the firm. We review how this research tradition has evolved over four decades. The review commences with a reassessment of the seminal ‘stage models’ that date back to the 1970s. It then proceeds to classify subsequent research on the basis of whether it includes process data and/or process theorizing. It is found that the majority of studies in this review do not combine process data with process theorizing. We show how, even in studies that contain some process elements, a process approach is not always sustained throughout the paper. On the basis of this review, six research themes are proposed, which would form the basis for a process agenda for future research.     

Dose‐Response Models Incorporating Aerosol Size Dependency for Francisella tularensis

The effect of bioaerosol size was incorporated into predictive dose‐response models for the effects of inhaled aerosols of Francisella tularensis (the causative agent of tularemia) on rhesus monkeys and guinea pigs with bioaerosol diameters ranging between 1.0 and 24 μm. Aerosol‐size‐dependent models were formulated as modification of the exponential and β‐Poisson dose‐response models and model parameters were estimated using maximum likelihood methods and multiple data sets of quantal dose‐response data for which aerosol sizes of inhaled doses were known. Analysis of F. tularensis dose‐response data was best fit by an exponential dose‐response model with a power function including the particle diameter size substituting for the rate parameter k scaling the applied dose. There were differences in the pathogen's aerosol‐size‐dependence equation and models that better represent the observed dose‐response results than the estimate derived from applying the model developed by the International Commission on Radiological Protection (ICRP, 1994) that relies on differential regional lung deposition for human particle exposure.     

An Extended Single‐index Model with Missing Response at Random

An extended single‐index model is considered when responses are missing at random. A three‐step estimation procedure is developed to define an estimator for the single‐index parameter vector by a joint estimating equation. The proposed estimator is shown to be asymptotically normal. An algorithm for computing this estimator is proposed. This algorithm only involves one‐dimensional nonparametric smoothers, thereby avoiding the data sparsity problem caused by high model dimensionality. Some simulation studies are conducted to investigate the finite sample performances of the proposed estimators.     

Relations Between Alphabetized Name Order and Nomination Counts in Peer Nomination Measures

Peer nominations, a central method for measuring peer relationships in developmental research, typically involve asking children or adolescents to choose peers who fit various criteria from an alphabetized roster of classmates or grade‐mates. Although such measures have been used for decades, very little research has investigated the effects of alphabetical name order on the number of nominations received by peers. This study collected peer nominations for 20 items among 607 eighth grade participants in two schools. Regression analyses showed that earlier name order significantly predicted higher nomination counts for eight of the items, and explained over 5 percent of the variance in four affective variables (friendship, acceptance, acquaintanceship, and received liking). Across variables, name order effects were negatively correlated with internal reliability of nominations, implying that order effects may be related to the consensus of the peer group. Name order also had a minimal effect on inter‐correlations among a subset of variables. Implications and concrete recommendations for controlling and reducing name order effects in future research are discussed.     

A Narrative Approach to Pregnancy‐related Discrimination and Leader–follower Relationships

This study sheds light on women's perceptions of pregnancy‐related discrimination committed by the discriminated woman's immediate leader. The purpose is to show how women describe this perception during pregnancy and after their return to working life after maternity leave. Further, the study explores the ways in which the quality of the leader–follower relationship is revealed during the narration process. The research draws on five individual stories, collected in two rounds of interviews. Representations of several kinds of discriminatory practices can be found in the narratives and reveal that even being a partner in a good‐quality leader–follower relationship does not necessarily protect a woman from pregnancy‐related discrimination. However, women involved in a high‐quality leader–follower relationship described their perceptions in a more positive manner than those in a low‐quality relationship. The contribution of the article to the literature is twofold: firstly, the results challenge the traditional view that high‐quality leader–member exchange relationships lead to positive outcomes. Secondly, examining the different ways in which people describe their perceptions of discrimination deepens our understanding of the equality problems that working women face.     

Symptoms of Eating Disorders Among Females in Drug Addiction Treatment

The aim of this study is to measure and describe symptoms of eating disorders among females in treatment for drug addiction in Norway. Previous clinical and epidemiological studies have revealed coprevalence between eating disorders and substance use or abuse. However, few studies have measured eating disorders in drug-using samples and even fewer within the context of drug treatment. In this study, 29 females with drug use disorder in residential treatment were tested with the Eating Disorder Inventory–2. A subgroup of 9 females (31%) with significant symptoms of eating disorders was identified. The characteristics of this group and possible clinical consequences are discussed.     

The effect of fast and slow decisions on risk taking

We experimentally compare fast and slow decisions in a series of experiments on financial risk taking in three countries involving over 1700 subjects. To manipulate fast and slow decisions, subjects were randomly allocated to responding within 7 seconds (time pressure) or waiting for at least 7 or 20 seconds (time delay) before responding. To control for different effects of time pressure and time delay on measurement noise, we estimate separate parameters for noise and risk preferences within a random utility framework. We find that time pressure increases risk aversion for gains and risk taking for losses compared to time delay, implying that time pressure increases the reflection effect of Prospect Theory. The results for gains are weaker and less robust than the results for losses. We find no significant difference between time pressure and time delay for loss aversion (tested in only one of the experiments). Time delay also leads to less measurement noise than time pressure and unconstrained decisions, and appears to be an effective way of decreasing noise in experiments.     

Infill asymptotics for adaptive kernel estimators of spatial intensity

We apply the Abramson principle to define adaptive kernel estimators for the intensity function of a spatial point process. We derive asymptotic expansions for the bias and variance under the regime that n independent copies of a simple point process in Euclidean space are superposed. The method is illustrated by means of a simple example and applied to tornado data.