When a candidate predictive marker is available, but evidence on its predictive ability is not sufficiently reliable, all‐comers trials with marker stratification are frequently conducted. We propose a framework for planning and evaluating prospective testing strategies in confirmatory, phase III marker‐stratified clinical trials based on a natural assumption on heterogeneity of treatment effects across marker‐defined subpopulations, where weak rather than strong control is permitted for multiple population tests. For phase III marker‐stratified trials, it is expected that treatment efficacy is established in a particular patient population, possibly in a marker‐defined subpopulation, and that the marker accuracy is assessed when the marker is used to restrict the indication or labelling of the treatment to a marker‐based subpopulation, ie, assessment of the clinical validity of the marker. In this paper, we develop statistical testing strategies based on criteria that are explicitly designated to the marker assessment, including those examining treatment effects in marker‐negative patients. As existing and developed statistical testing strategies can assert treatment efficacy for either the overall patient population or the marker‐positive subpopulation, we also develop criteria for evaluating the operating characteristics of the statistical testing strategies based on the probabilities of asserting treatment efficacy across marker subpopulations. Numerical evaluations to compare the statistical testing strategies based on the developed criteria are provided. 相似文献
The classical unconditional exact p-value test can be used to compare two multinomial distributions with small samples. This general hypothesis requires parameter estimation under the null which makes the test severely conservative. Similar property has been observed for Fisher's exact test with Barnard and Boschloo providing distinct adjustments that produce more powerful testing approaches. In this study, we develop a novel adjustment for the conservativeness of the unconditional multinomial exact p-value test that produces nominal type I error rate and increased power in comparison to all alternative approaches. We used a large simulation study to empirically estimate the 5th percentiles of the distributions of the p-values of the exact test over a range of scenarios and implemented a regression model to predict the values for two-sample multinomial settings. Our results show that the new test is uniformly more powerful than Fisher's, Barnard's, and Boschloo's tests with gains in power as large as several hundred percent in certain scenarios. Lastly, we provide a real-life data example where the unadjusted unconditional exact test wrongly fails to reject the null hypothesis and the corrected unconditional exact test rejects the null appropriately. 相似文献
We propose a class of ratio tests that is applicable whenever a cumulation (of transformed) data is asymptotically normal upon appropriate normalization. The Karhunen–Loève theorem is employed to compute weighted averages. The test statistics are ratios of quadratic forms of these averages and hence scale-invariant, also called self-normalizing: The scaling parameter cancels asymptotically. Limiting distributions are obtained. Critical values and asymptotic local power functions can be calculated by standard numerical means. The ratio tests are directed against local alternatives and turn out to be almost as powerful as optimal competitors, without being plagued by nuisance parameters at the same time. Also in finite samples they perform well relative to self-normalizing competitors. 相似文献
Social diffusion of information amplifies risk through processes of birth, death, and distortion of message content. Dread risk—involving uncontrollable, fatal, involuntary, and catastrophic outcomes (e.g., terrorist attacks and nuclear accidents)—may be particularly susceptible to amplification because of the psychological biases inherent in dread risk avoidance. To test this, initially balanced information about high or low dread topics was given to a set of individuals who then communicated this information through diffusion chains, each person passing a message to the next. A subset of these chains were also reexposed to the original information. We measured prior knowledge, perceived risk before and after transmission, and, at each link, number of positive and negative statements. Results showed that the more a message was transmitted the more negative statements it contained. This was highest for the high dread topic. Increased perceived risk and production of negative messages was closely related to the amount of negative information that was received, with domain knowledge mitigating this effect. Reexposure to the initial information was ineffectual in reducing bias, demonstrating the enhanced danger of socially transmitted information. 相似文献
Information before unblinding regarding the success of confirmatory clinical trials is highly uncertain. Current techniques using point estimates of auxiliary parameters for estimating expected blinded sample size: (i) fail to describe the range of likely sample sizes obtained after the anticipated data are observed, and (ii) fail to adjust to the changing patient population. Sequential MCMC-based algorithms are implemented for purposes of sample size adjustments. The uncertainty arising from clinical trials is characterized by filtering later auxiliary parameters through their earlier counterparts and employing posterior distributions to estimate sample size and power. The use of approximate expected power estimates to determine the required additional sample size are closely related to techniques employing Simple Adjustments or the EM algorithm. By contrast with these, our proposed methodology provides intervals for the expected sample size using the posterior distribution of auxiliary parameters. Future decisions about additional subjects are better informed due to our ability to account for subject response heterogeneity over time. We apply the proposed methodologies to a depression trial. Our proposed blinded procedures should be considered for most studies due to ease of implementation. 相似文献
In the contemporary multicentric world, sovereign states have to manage carefully the construction of their image, defining their role and aspirations. With the re-definition of the state centric politics, stories become relevant: communication is a form of power, and networked forms of communication are becoming progressively a way to conquer the transnational public spheres. Through strategic narratives of foreign politics, states try to set up the ‘tales’ of international affairs and foreign strategies, to suggest a world vision, a causal interpretation, determining frames that affect transnational actors’ position in the international environment. Sovereign states develop these kind of frame using tools and theories referred to the commercial branding tradition to promote and support their own policies and identity. We decided to investigate how that process is made through information diffusion on digital platforms.
In this work, it has been analyzed the content presented through Twitter posts by the Foreign Ministries accounts of four different States dissimilar for geopolitical positioning and security concerns (USA; Israel; France; Sweden), for a period of three months (9/1/2015-11/30/2015); leading to the identification of different models and characteristic patterns of self-representation.
The thematic content analysis, based on the identification of macrocategories and micro-issues, has led to the identification of different models and characteristic patterns of self-representation, determined by domestic vicissitudes, and has shown some regularities, caused by the branding vocation of autobiographical online contents. 相似文献
This study examined how Turkey uses social media as a tool for public diplomacy and how the state’s soft-power efforts have recently changed on the global stage. The researchers constructed a dataset of 2769 Twitter posts by the Turkish government’s most influential public diplomacy accounts. The analyses revealed that the focus of Turkey’s Twitter public diplomacy has become concentrated on the Middle East and North Africa (MENA) region and is thematically focused on the political values embodied by the Turkish president. The findings suggest that public diplomacy remains to be the diplomacy of the government, not of the public, and social media is used as just another tool for propaganda, not as a means of engagement with foreign publics. Further, the findings indicate the emergence of a “new” cult of personality in public diplomacy and point out the instrumental role of social media in changing the dynamics of leader-follower relationship. The study contributes to public relations theory and practice by advancing the burgeoning public diplomacy scholarship at the intersection of social media and relational approaches. 相似文献