Statistical considerations in clinical trial design with event-free survival as the primary efficacy endpoint

In late-phase confirmatory clinical trials in the oncology field, time-to-event (TTE) endpoints are commonly used as primary endpoints for establishing the efficacy of investigational therapies. Among these TTE endpoints, overall survival (OS) is always considered as the gold standard. However, OS data can take years to mature, and its use for measurement of efficacy can be confounded by the use of post-treatment rescue therapies or supportive care. Therefore, to accelerate the development process and better characterize the treatment effect of new investigational therapies, other TTE endpoints such as progression-free survival and event-free survival (EFS) are applied as primary efficacy endpoints in some confirmatory trials, either as a surrogate for OS or as a direct measure of clinical benefits. For evaluating novel treatments for acute myeloid leukemia, EFS has been gradually recognized as a direct measure of clinical benefits. However, the application of an EFS endpoint is still controversial mainly due to the debate surrounding definition of treatment failure (TF) events. In this article, we investigate the EFS endpoint with the most conservative definition for the timing of TF, which is Day 1 since randomization. Specifically, the corresponding non-proportional hazard pattern of the EFS endpoint is investigated with both analytical and numerical approaches.     

Calculation of age-specific fertility schedules from tabulations of parity in two censuses

The mathematics of stable populations recently has been generalized to cover populations with time-varying fertility and mortality by a modification incorporating the sum of age-varying growth rates in place of the fixed growth rate of a stable population. Equations that characterize nonstable populations apply to any cohort-like phenomenon with a measurable property that cumulates gains or losses through time. In particular, the equations fit the relation between a population's average parity at a given age and age-specific fertility rates previously experienced at lower ages. Techniques devised to derive an intercensal life table from single-year age distributions in two censuses are adapted to estimate accurate intercensal fertility schedules from distributions of parity by age of woman in two censuses. Birth-order specific fertility schedules are also estimated.     

Movement and structure as determinants of spatial representations

It was hypothesized that the cognitive representation of distances between locations in an environment is a function not only of the environment's structure, but also of a person's pattern of travel within the environment. In the present study subjects were exposed to an experimental environment in which some locations were separated either by an opaque or a transparent barrier and other locations were not separated by any barrier. As subjects learned where the locations were, they were required to follow a specific route that allowed travel between some locations in each category but not others. Afterward subjects were asked to reproduce from memory the separation between pairs of locations. The results supported the hypothesis. Recalled distance between locations was significantly affected by both movement patterns of subjects and structural aspects of the environment (type of barrier and actual separation between locations). These results are interpreted in terms of the types of information made available through particular movement patterns and the corresponding salience of that information.     

Business Legitimacy among Business Students in the United States, Great Britain, and South Africa

This study compares attitudes toward business legitimacy in three countries. Positive attitudes toward business legitimacy exist when there is a congruence between organizational activities and societal expectations. Businesses are concerned about the extent to which negative attitudes toward business legitimacy will lead to increased government regulation. The results suggest that business students in all three countries are similar in their attitudes toward business legitimacy; however, blacks have more negative attitudes toward business legitimacy than do whites. This study resulted in the validation of a scale that can be used to measure attitudes toward business legitimacy on a cross-cultural basis. Business legitimacy is a major concern in South Africa as the predominately white business community seeks to give the emerging black majority a stake in the existing economic system. This revised version was published online in August 2006 with corrections to the Cover Date.