Efficient Design and Inference for Multi-stage Randomized Trials of Individualized Treatment Policies

Increased clinical interest in individualized ‘adaptive’ treatment policies has shifted the methodological focus for their development from the analysis of naturalistically observed strategies to experimental evaluation of a pre-selected set of strategies via multi-stage designs. Because multi-stage studies often avoid the ‘curse of dimensionality’ inherent in uncontrolled studies, and hence the need to parametrically smooth trial data, it is not surprising in this context to find direct connections among different methodological approaches. We show by asymptotic and algebraic proof that the maximum likelihood (ML) and optimal semi-parametric estimators of the mean of a treatment policy and its standard error are equal under certain experimental conditions. The two methodologies offer conceptually different formulations, which we exploit to develop a unified and efficient approach to design and inference for multi-stage trials of policies that adapt treatment according to discrete responses. We derive a sample size formula expressed in terms of a parametric (regression-based) version of the optimal semi-parametric population variance. Non-parametric (sample-based) ML estimation performed well in simulation studies, in terms of achieved power, even though sample sizes relied on parametric re-expression. For a variety of simulated scenarios, ML outperformed the semi-parametric approach, which used a priori rather than estimated randomization probabilities, because the test statistic was sensitive to even small differences arising in finite samples

Software for Distributed Computation on Medical Databases: A Demonstration Project

Bringing together the information latent in distributed medical databases promises to personalize medical care by enabling reliable, stable modeling of outcomes with rich feature sets (including patient characteristics and treatments received). However, there are barriers to aggregation of medical data, due to lack of standardization of ontologies, privacy concerns, proprietary attitudes toward data, and a reluctance to give up control over end use. Aggregation of data is not always necessary for model fitting. In models based on maximizing a likelihood, the computations can be distributed, with aggregation limited to the intermediate results of calculations on local data, rather than raw data. Distributed fitting is also possible for singular value decomposition. There has been work on the technical aspects of shared computation for particular applications, but little has been published on the software needed to support the "social networking" aspect of shared computing, to reduce the barriers to collaboration. We describe a set of software tools that allow the rapid assembly of a collaborative computational project, based on the flexible and extensible R statistical software and other open source packages, that can work across a heterogeneous collection of database environments, with full transparency to allow local officials concerned with privacy protections to validate the safety of the method. We describe the principles, architecture, and successful test results for the site-stratified Cox model and rank-k Singular Value Decomposition (SVD)

Recurrence of bipolar disorders and major depression

Objective: : It is not known whether the risk of recurrence declines with time in bipolar disorders and in major depression. This study describes the life-long recurrence risk of bipolar I, bipolar II and major depressive disorders. Method: : 160 bipolar-I, 60 bipolar-II and 186 depressive patients hospitalised between 1959 and 1963 were followed up every five years from 1965 to 1985. The course prior to the index hospitalisation was assessed in retrospect. The recurrence risk was computed by the multiplicative intensity model (Aalen et al. 1980). Results: : The cumulative intensity curves for the transition from states of remission to new episodes remained linear over 30 to 40 years after onset, indicating a constant risk of recurrence over the life-span up to the age of 70 or more. The recurrence risk of bipolar disorders (0.40 episodes per year) was about twice that of depression (0.20 episodes per year); BP-II disorders had only a slightly higher recurrence risk than BP-I disorders. There were no significant gender differences in the course of either bipolar or depressive disorders. Conclusion: : If long-term trials confirm its efficacy, these results support lifelong prophylactic treatment of severe types of mood disorder

A point-of-care clinical trial comparing insulin administered using a sliding scale versus a weight-based regimen

Background Clinical trials are widely considered the gold standard in comparative effectiveness research (CER) but the high cost and complexity of traditional trials and concerns about generalizability to broad patient populations and general clinical practice limit their appeal. Unsuccessful implementation of CER results limits the value of even the highest quality trials. Planning for a trial comparing two standard strategies of insulin administration for hospitalized patients led us to develop a new method for a clinical trial designed to be embedded directly into the clinical care setting thereby lowering the cost, increasing the pragmatic nature of the overall trial, strengthening implementation, and creating an integrated environment of research-based care

Международный музыкальный конкурс в формировании имиджа страны проведения (на примере Евровидения 2017)

Аннотация выпускной квалификационной работы Орлов Никита Сергеевич «МЕЖДУНАРОДНЫЙ МУЗЫКАЛЬНЫЙ КОНКУРС В ФОРМИРОВАНИИ ИМИДЖА СТРАНЫ ПРОВЕДЕНИЯ (НА ПРИМЕРЕ ЕВРОВИДЕНИЯ-2017)» Н. рук. - Быкова Елена Владимировна, доктор филологических наук, доцент Кафедра связей с общественностью Очная форма обучения Актуальность: международный музыкальный конкурс Евровидение как самое масштабное регулярное высокотехнологичное телевизионное и медиа-событие, которое . Е ежегодно акцентирует внимание аудитории на национально-культурных особенностях страны-организатора конкурса, формирует значительные туристические потоки и тем самым способствует формированию имиджа территории. Более того, победа страны-участницы конкурса Евровидения зачастую отражает идеолого-политический вектор Европы и по сути дела выполняет функцию политического PR страны-победителя и страны-хозяйки мероприятия. Следовательно анализ используемых на мероприятии коммуникативных технологий является актуальным и востребованным для событийного и устроительного PR Объект исследования: коммуникационные активности международного музыкального конкурса (на примере Евровидения в Киеве в 2017 г.). Предмет исследования: функция статусного PR-мероприятия в формировании имиджа страны. Цель исследования: доказать, что международный музыкальный конкурс Евровидение способствует формированию имиджа страны проведения. Задачи исследования: разработать терминологический аппарат исследования на основе научной литературы по имиджмейкингу, брендингу и ивент-менеджменту; определить актуальные коммуникационные технологии, применяемые в рамках специальных событий для формирования имиджа страны; описать роль Европейского Вещательного Союза как организатора Евровидения в формировании имиджа страны проведения конкурса; оценить эффективность реализованных коммуникативных технологий формирования имиджа страны в рамках Евровидения; дать рекомендации по формированию имиджа страны с помощью Евровидения. Теоретическая база: научные труды Е. Быковой, Д. Гавры, А. Панкрухина, Б. Дженеса, Е. Кавериной, У. Хальцбаура, Дж. Голдблатта а также труды Д. Пассмана о музыкальном бизнесе, П. Джордана о продвижении имиджа стран с помощью Евровидения и др. Эмпирическая база: PR-документы, размещенные на сайте Евровидения и Европейского Вещательного Союза; более полутора миллиона статей об Украине в европейских СМИ, размещенные в базе проекта мониторинга международного имиджа Украины «Oko»; данные базы материалов СМИ и социальных медиа Factiva; данные Google.Analytics. Практическая значимость: исследование доказывает, что международный музыкальный конкурс Евровидение формирует имидж страны проведения независимо от успешности использования конкретных технологий формирования имиджа страны. Тезисы исследования были апробированы на международном научном форуме «Медиа в современном мире. 57-е Петербургские чтения», опубликованы в сборнике материалов статей форума и имеют статус научной статьи, размещенной в базе РИНЦ. Структура работы: Работа состоит из введения, 3 глав: «функция специального события в формировании имиджа страны», «Евровидение как специальное событие Европейского Вещательного Союза» и «коммуникационный потенциал Евровидения как площадки для формирования имиджа страны», заключения, списка использованной литературы из 67 позиций и 12 приложений. Общий объем 76 страниц.Abstract of graduating qualification thesis Mikita Arlou INTERNATIONAL MUSIC CONTEST IN HOST COUNTRY IMAGE FORMATION (ON THE EXAMPLE OF EUROVISION 2017) Supervisor associate professor Elena Bykova, doctor of philology Department of PR in business full-time study Relevance: the international music contest Eurovision as the most wide scale regular high tech TV and Media event which annually emphasizes audience attention on national cultural features of the host country, forms tourist flows which have huge influence on territorial image formation. Besides the win of a participating in the Eurovision country often shows the ideological and political European vector and in fact serves as political PR of the winning or host country. Consequently the analysis of applied communication technologies is relevant and in-demand for event PR. Research object: communication activities of international music contest (on the example of Eurovision in Kyiv in 2017). Research subject: function of status PR event in country image formation. The aim of research: to prove that international music contest Eurovision contributes host country image formation. The tasks of research: to develop research terminology based on scientific literature on image making, branding and event management; to define actual communication technologies applied in special PR events on country image formation; to describe European Broadcasting Union role in host country image formation; to appreciate effectiveness of applied communication technologies on host country image formation in Eurovision; to give recommendations for host country image formation with the help of Eurovision. Theoretical base: scientific works written by E. Bykova, D. Gavra, A. Pankrukhin, B. Jenes, E. Kaverina, U. Halcbaur, J. Goldblatt and D. Passman´s works on music business and P. Jordan on county image building with the help of Eurovision, etc. The empirical base: PR documents from official Eurovision and European Broadcasting Union websites; more than 1.5 million articles on Ukraine in European media stored in the base of international Ukrainian image monitoring project Oko; content of the mass media and social media base Factiva; Google.Analytics data. Practical significance: the research proves that international music contest Eurovision is relevant for the host country image formation independently of the success level of applied country image formation communication technologies. Approbation: General positions of current thesis were aprobated on international scientific forum Media in modern world and were published at the collection of articles of the forum and have the status of a scientific article posted in the RINC database. Thesis structure: Research consists of introduction, 3 chapters: Special event function in country image formation, Eurovision as EBU special event and communication potential of Eurovision as a platform for image formation; conclusion, literature list from 67 positions and 12 attachments. The total volume is 76 pages

SEQUENTIAL METHODS FOR COMPARATIVE EFFECTIVENESS EXPERIMENTS: POINT OF CARE CLINICAL TRIALS

Abstract: The goal of comparative effectiveness research (CER) is to support evidence-based choices of treatments. Currently the majority of randomized trials for CER are designed to demonstrate superiority, which often require large sample size because the effect sizes between treatments in current use are typically small to moderate and there are usually more than two treatments to be compared. We propose an alternative group sequential design for such setting. Instead of testing superiority, we aim to select high quality treatments that are within a small distance from the best treatment. The basic idea is to eliminate non-promising treatments at interim analyses that cannot be much better than the currently observed best treatment, based on generalized likelihood ratio tests. This approach can also be used for guideline implementation and for phase II selection trials