Adaptive Survival Trials

Mid-study design modifications are becoming increasingly accepted in confirmatory clinical trials, so long as appropriate methods are applied such that error rates are controlled. It is therefore unfortunate that the important case of time-to-event endpoints is not easily handled by the standard theory. We analyze current methods that allow design modifications to be based on the full interim data, i.e., not only the observed event times but also secondary endpoint and safety data from patients who are yet to have an event. We show that the final test statistic may ignore a substantial subset of the observed event times. Since it is the data corresponding to the earliest recruited patients that is ignored, this neglect becomes egregious when there is specific interest in learning about long-term survival. An alternative test incorporating all event times is proposed, where a conservative assumption is made in order to guarantee type I error control. We examine the properties of our proposed approach using the example of a clinical trial comparing two cancer therapies.Comment: 22 pages, 7 figure

Managing Policy: Executive Agencies of the European Commission. IHS Political Science Series Working Paper No. 146, September 2017

'Agencification' in the European Union has emerged as an important research topic at the intersection between political science and organizational studies. This Working Paper focuses on a group of six agencies under the wings of the European Commission that is often overlooked in the literature, despite the fact that these agencies are now set up for more than a decade, and despite the fact that their portfolio is growing. It sheds light on the historical context of their establishment and their legal foundation, looks at their organizational structure, and investigates the fields of action in which they are tasked to operate

His and Her Tort Reform: Gender Injustice in Disguise

This Article is an inquiry into the gendered nature of tort remedies. Modem tort law provides increased protection for injuries suffered by women. Drawing upon a national study of punitive damages in products liability and medical malpractice, Professors Koenig and Rustad argue that tort remedies are bifurcated into his and her tort worlds based upon gender roles. Nearly half of the punitive damages verdicts awarded to women stemmed from injuries caused by household consumer products and dangerously defective drugs or medical devices. In contrast, the punitive damages awarded to males arose from accidents involving industrial and farm machinery, asbestos, chemicals, containers, and vehicles. Two out of three plaintiffs receiving punitive damages awards in medical malpractice litigation are women. Women employ this remedy primarily to obtain redress for mismanaged child birth, cosmetic surgery, sexual abuse, and neglect in nursing homes—gender-based injuries. Women are also far more likely than men to be awarded noneconomic damages in medical products liability litigation. Consequently, proposed restrictions on non-economic damages and the Food and Drug Administration defense to punitive damages will have a disparate impact on women\u27s mass tort remedies. Similarly, limitations on medical malpractice remedies will disproportionately restrict pain and suffering awards as well as punitive damages to women. Without systematic analysis of the distinctive ways that tort law relates to gender, women\u27s voices will not be heard in the tort reform debate

Crimtorts as Corporate Just Deserts

Just as Grant Gilmore described contorts that lie on the borderline between contract and tort law, the authors coin the term crimtort to identify the expanding common ground between criminal and tort law. Although the concept of crimtort can be broadly applied to many areas of the law, this Article focuses on the primary crimtort remedy - punitive damages. The deterrent power of punitive damages lies in the wealth-calibration of the defendant\u27s punishment. For corporations this means that punitive damages will reflect the firm\u27s net income or net worth. The theoretical danger is that juries will abuse wealth by redistributing corporate assets in disregard of the purposes of civil punishment. To support their argument that wealth is not being widely misused, the authors present an empirical study of a decade of crimtort cases in which federal appeals courts upheld punitive damages of $1 million or more. However, even though punitive damage verdicts are generally proportional to corporate wealth, individual cases such as Exxon Valdez raise troubling due process issues. The authors propose instituting middle-range procedural protection for crimtort defendants in order to accommodate the quasi-criminal objectives of this legal hybrid

A Method to Determine the Presence of Averaged Event-Related Fields Using Randomization Tests

We present a simple and effective method to test whether an event consistently activates a set of brain electric sources across repeated measurements of event-related scalp field data. These repeated measurements can be single trials, single subject ERPs, or ERPs from different studies. The method considers all sensors simultaneously, but can be applied separately to each time frame or frequency band of the data. This allows limiting the analysis to time periods and frequency bands where there is positive evidence of a consistent relation between the event and some brain electric sources. The test may therefore avoid false conclusions about the data resulting from an inadequate selection of the analysis window and bandpass filter, and permit the exploration of alternate hypotheses when group/condition differences are observed in evoked field data. The test will be called topographic consistency test (TCT). The statistical inference is based on simple randomization techniques. Apart form the methodological introduction, the paper contains a series of simulations testing the statistical power of the method as function of number of sensors and observations, a sample analysis of EEG potentials related to self-initiated finger movements, and Matlab source code to facilitate the implementation. Furthermore a series of measures to control for multiple testing are introduced and applied to the sample dat

Do Britons and other Europeans disagree on policy issues? The answer might surprise you

Eurosceptics in the UK and elsewhere often argue that the EU subverts democracy by forcing countries with different values and economic systems to follow the same rules. The Vote Leave Campaign, for instance, laments that “Politicians have surrendered the UK’s power to veto laws we disagree with, so if the EU decides to introduce a law that will be bad for Britain there is nothing we can do to stop it.” But is it true that Britons and other Europeans want different things? Does European integration cause people in Britain, and possibly other member states, to be systematically outvoted on the policies they care most about, and thus find themselves relegated to a position of “permanent minorities”? Research by Thomas Hale and Mathias Koenig-Archibugi provides some surprising answers to this question