Patient selection for oncology phase I trials: a multi-institutional study of prognostic factors.

PURPOSE The appropriate selection of patients for early clinical trials presents a major challenge. Previous analyses focusing on this problem were limited by small size and by interpractice heterogeneity. This study aims to define prognostic factors to guide risk-benefit assessments by using a large patient database from multiple phase I trials. PATIENTS AND METHODS Data were collected from 2,182 eligible patients treated in phase I trials between 2005 and 2007 in 14 European institutions. We derived and validated independent prognostic factors for 90-day mortality by using multivariate logistic regression analysis. Results The 90-day mortality was 16.5% with a drug-related death rate of 0.4%. Trial discontinuation within 3 weeks occurred in 14% of patients primarily because of disease progression. Eight different prognostic variables for 90-day mortality were validated: performance status (PS), albumin, lactate dehydrogenase, alkaline phosphatase, number of metastatic sites, clinical tumor growth rate, lymphocytes, and WBC. Two different models of prognostic scores for 90-day mortality were generated by using these factors, including or excluding PS; both achieved specificities of more than 85% and sensitivities of approximately 50% when using a score cutoff of 5 or higher. These models were not superior to the previously published Royal Marsden Hospital score in their ability to predict 90-day mortality. CONCLUSION Patient selection using any of these prognostic scores will reduce non-drug-related 90-day mortality among patients enrolled in phase I trials by 50%. However, this can be achieved only by an overall reduction in recruitment to phase I studies of 20%, more than half of whom would in fact have survived beyond 90 days.

Do Foreign Greenfields Outperform Foreign Acquisitions or Vice Versa? An Institutional Perspective.

Prior studies of the comparative performance of greenfields and acquisitions have advanced competing arguments, with some arguing that greenfields should outperform acquisitions because acquisitions are costlier to integrate, and others that acquisitions should outperform greenfields because greenfields suffer from a liability of newness. Moreover, while the costs of integration and the liability of newness are at their greatest during a subsidiary's first years, prior studies have tested their competing arguments on samples containing older subsidiaries. We extend these prior studies by (1) developing an institutional theory-based framework that simultaneously considers the costs of integration and the liability of newness, (2) recognizing that both types of costs vary with the level of subsidiary integration, and (3) focusing on the stage of their life during which subsidiaries predominantly incur these costs. To measure subsidiary performance, we ask managers of Dutch multinationals how their ex ante performance expectations compare to the subsidiary's ex post performance during its first two years. Analysing a sample of 191 foreign subsidiaries and controlling for entry mode self-selection and other factors, we find that acquisitions outperform greenfields at low and intermediate levels of subsidiary integration, but that greenfields outperform acquisitions at higher integration levels. [ABSTRACT FROM AUTHOR]

An Inconvenient Truth: Barriers to Truth Recovery in the Aftermath of Institutional Child Abuse in Ireland

Contemporary settled democracies, including the United States, England and Wales and Ireland, have witnessed a string of high profile cases of institutional child abuse in both church and state settings. Set against the broader literature on transitional justice, this analysis argues that there are significant barriers to truth recovery within the particular context of historical institutional abuse by the clergy in the Republic of Ireland. In the main, I argue that the frameworks of the inquiries and commissions into historical institutional child abuse are not conducive to truth recovery or the search for justice in dealing with the legacy of an abusive past. It is the church-state relationship which makes the Irish situation noteworthy and unique. The Catholic Church and child care institutions are especially self-protective, secretive and closed by nature and strongly discourage the drawing of attention to any deficiencies in organisational procedures. The nature of the public inquiry process also means that there is often a rather linear focus on accountability and apportioning blame. Collectively, such difficulties inhibit fuller systemic investigation of the veracity of what actually happened and, in turn, meaningful modification of child care policies. The article concludes by offering some thoughts on implications for transitional justice discourses more broadly as well as the residual issues for Ireland and other settled democracies in terms of moving on from the legacy of institutional child abuse.

'Grooming' and the Sexual Abuse of Children:Institutional, Internet and Familial Dimensions

‘Grooming’ and the Sexual Abuse of Children: Institutional, Internet and Familial Dimensions critically examines the official and popular discourses on grooming, predominantly framed within the context of on-line sexual exploitation and abuse committed by strangers, and institutional child abuse committed by those in positions of trust.

Set against the broader theoretical framework of risk, security and governance, this book argues that due to the difficulties of drawing clear boundaries between innocuous and harmful motivations towards children, pre-emptive risk-based criminal law and policy are inherently limited in preventing, targeting and criminalising ‘grooming’ behaviour prior to the manifestation of actual harm. Through examination of grooming against the complexities of the onset of sexual offending against children and its actual role in this process, the author broadens existing discourses by providing a fuller, more nuanced conceptualisation of grooming, including its role in intra-familial and extra-familial contexts. There is also timely discussion of new and emerging forms of grooming, such as ‘street’ or ‘localised’ grooming, as typified by recent cases in Rochdale and Oldham, and ‘peer-to-peer’ grooming.

The first inter-disciplinary, thematic, and empirical investigation of grooming in a multi-jurisdictional context, ‘Grooming’ and the Sexual Abuse of Children draws on extensive empirical research in the form of over fifty interviews with professionals, working in the fields of sex offender risk assessment, management or treatment, as well as child protection or victim support in the four jurisdictions of the United Kingdom and the Republic of Ireland. Impeccably presented and meticulously considered, this book will be of interest to criminologists and those working and studying in the field of policing and criminal justice studies, as well as policy makers and practitioners in the areas of child protection and sex offender management.