The Jewish-Palestinian Encounter in a Time of Crisis

For over two decades the School for Peace at Neve Shalom/Wahat al-Salam has been bringing together Jews and Arabs for dialogue workshops. This article examines the unique approach that the School for Peace has developed over the years in the light of existing theory in the field and of existing research in the field of social identity construction and majority-minority relations. The article then shows how processes that take place in our encounter workshops may even shed light on the Jewish-Palestinian conflict from 1948 until today. Understanding these processes is essential to any attempt at building a more humane society based on equality and justice between the two peoples.     

Sample size selection in clinical trials when population means are subject to a partial order: one-sided ordered alternatives

The statistical methodology under order restriction is very mathematical and complex. Thus, we provide a brief methodological background of order-restricted likelihood ratio tests for the normal theoretical case for the basic understanding of its applications, and relegate more technical details to the appendices. For data analysis, algorithms for computing the order-restricted estimates and computation of p-values are described. A two-step procedure is presented for obtaining the sample size in clinical trials when the minimum power, say 0.80 or 0.90 is specified, and the normal means satisfy an order restriction. Using this approach will result in reduction of 14-24% in the sample size required when one-sided ordered alternatives are used, as illustrated by several examples.     

Group-sequential logrank methods for trial designs using bivariate non-competing event-time outcomes

We discuss the multivariate (2L-variate) correlation structure and the asymptotic distribution for the group-sequential weighted logrank statistics formulated when monitoring two correlated event-time outcomes in clinical trials. The asymptotic distribution and the variance–covariance for the 2L-variate weighted logrank statistic are derived as available in various group-sequential trial designs. These methods are used to determine a group-sequential testing procedure based on calendar times or information fractions. We apply the theoretical results to a group-sequential method for monitoring a clinical trial with early stopping for efficacy when the trial is designed to evaluate the joint effect on two correlated event-time outcomes. We illustrate the method with application to a clinical trial and describe how to calculate the required sample sizes and numbers of events.

     

A novel test to compare two treatments based on endpoints involving both nonfatal and fatal events

In a clinical trial comparing two treatment groups, one commonly‐used endpoint is time to death. Another is time until the first nonfatal event (if there is one) or until death (if not). Both endpoints have drawbacks. The wrong choice may adversely affect the value of the study by impairing power if deaths are too few (with the first endpoint) or by lessening the role of mortality if not (with the second endpoint). We propose a compromise that provides a simple test based on the time to death if the patient has died or time since randomization augmented by an increment otherwise. The test applies the ordinary two‐sample Wilcoxon statistic to these values. The formula for the increment (the same for experimental and control patients) must be specified before the trial starts. In the simplest (and perhaps most useful) case, the increment assumes only two values, according to whether or not the (surviving) patient had a nonfatal event. More generally, the increment depends on the time of the first nonfatal event, if any, and the time since randomization. The test has correct Type I error even though it does not handle censoring in a customary way. For conditions where investigators would face no easy (advance) choice between the two older tests, simulation results favor the new test. An example using a renal‐cancer trial is presented. Copyright © 2015 John Wiley & Sons, Ltd.     

A semiparametric modeling approach for analyzing clinical biomarkers restricted to limits of detection

Before biomarkers can be used in clinical trials or patients' management, the laboratory assays that measure their levels have to go through development and analytical validation. One of the most critical performance metrics for validation of any assay is related to the minimum amount of values that can be detected and any value below this limit is referred to as below the limit of detection (LOD). Most of the existing approaches that model such biomarkers, restricted by LOD, are parametric in nature. These parametric models, however, heavily depend on the distributional assumptions, and can result in loss of precision under the model or the distributional misspecifications. Using an example from a prostate cancer clinical trial, we show how a critical relationship between serum androgen biomarker and a prognostic factor of overall survival is completely missed by the widely used parametric Tobit model. Motivated by this example, we implement a semiparametric approach, through a pseudo-value technique, that effectively captures the important relationship between the LOD restricted serum androgen and the prognostic factor. Our simulations show that the pseudo-value based semiparametric model outperforms a commonly used parametric model for modeling below LOD biomarkers by having lower mean square errors of estimation.     

Estimand framework: Are we asking the right questions? A case study in the solid tumor setting

The estimand framework requires a precise definition of the clinical question of interest (the estimand) as different ways of accounting for “intercurrent” events post randomization may result in different scientific questions. The initiation of subsequent therapy is common in oncology clinical trials and is considered an intercurrent event if the start of such therapy occurs prior to a recurrence or progression event. Three possible ways to account for this intercurrent event in the analysis are to censor at initiation, consider recurrence or progression events (including death) that occur before and after the initiation of subsequent therapy, or consider the start of subsequent therapy as an event in and of itself. The new estimand framework clarifies that these analyses address different questions (“does the drug delay recurrence if no patient had received subsequent therapy?” vs “does the drug delay recurrence with or without subsequent therapy?” vs “does the drug delay recurrence or start of subsequent therapy?”). The framework facilitates discussions during clinical trial planning and design to ensure alignment between the key question of interest, the analysis, and interpretation. This article is a result of a cross-industry collaboration to connect the International Council for Harmonisation E9 addendum concepts to applications. Data from previously reported randomized phase 3 studies in the renal cell carcinoma setting are used to consider common intercurrent events in solid tumor studies, and to illustrate different scientific questions and the consequences of the estimand choice for study design, data collection, analysis, and interpretation.     

Arab students in a Hebrew university – existing but unnoticed

This article focuses on ways in which Arab students cope with challenges of integrating into the academic life of a Hebrew university in Israel. From this research we can learn that the students face considerable hardships during their university studies. Some of these hardships derive from language barriers. In addition, findings show that the Arab students face different forms of exclusion by the university. These create a sense of alienation, estrangement and even hostility.