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.

Theoretical and spatial limits to the value of rural environmental benefits: Evidence from the forestry sector

The valuation of environmental benefits has been well researched in the forestry sector. This is not generally the case in the agriculture sector although schemes to compensate farmers for provision of officially defined environmental benefits are already in place throughout the European Union. This paper draws on empirical findings from forestry and deductions from economic theory to challenge the notion of the universality of such benefits. Empirical findings from forestry suggest recreational use value is location specific rather than widely spread. Household utility theory predicts zero willingness to pay to maintain the status quo level of a previously unpaid for environmental benefit (when provision is not perceived as under risk) but a positive willingness to pay for an increase. Thus, non use values cannot be attributed to the major part of existing commercial forestry area but to spatially restricted schemes such as additional afforestation or preservation of ancient natural woodlands.