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.

Applying an International Human Rights Framework to State Budget Allocations: Rights and Resources

Human rights based budget analysis projects have emerged at a time when the United Nations has asserted the indivisibility of all human rights and attention is increasingly focused on the role of non-judicial bodies in promoting and protecting human rights. This book seeks to develop the human rights framework for such budget analyses, by exploring the international law obligations of the International Covenant on Economic, Social and Cultural Rights (ICESCR) in relation to budgetary processes. The book outlines international experiences and comparative practice in relation to economic and social rights budget analysis and budgeting.

The book sets out an ICESCR-based methodology for analysing budget and resource allocations and focuses on the legal obligation imposed on state parties by article 2(1) of ICESCR to progressively realise economic and social rights to 'the maximum of available resources'. Taking Northern Ireland as a key case study, the book demonstrates and promotes the use of a ‘rights-based’ approach in budgetary decision-making.

The book will be relevant to a global audience currently considering how to engage in the budget process from a human rights perspective. It will be of interest to students and researchers of international human rights law and public law, as well as economic and social rights advocacy and lobbying groups.