Detection of biological and chemical threats is an important consideration in the modern national defense policy. Much of the testing and evaluation of threat detection technologies is performed without appropriate uncertainty quantification. This paper proposes an approach to analyzing the effect of threat concentration on the probability of detecting chemical and biological threats. The approach uses a probit semi-parametric formulation between threat concentration level and the probability of instrument detection. It also utilizes a bayesian adaptive design to determine at which threat concentrations the tests should be performed. The approach offers unique advantages, namely, the flexibility to model non-monotone curves and the ability to test in a more informative way. We compare the performance of this approach to current threat detection models and designs via a simulation study.

In recent times, there has been an increasing interest in adaptive designs for clinical trials. As opposed to conventional designs, adaptive designs allow flexible design adaptation in the middle of a trial based on accumulated data. Although various models have been developed using both frequentist and Bayesian perspectives, relative statistical performances of adaptive designs are somewhat controversial and little is known about those of Bayesian adaptive designs. Most comparison studies also focused on single experimental treatment rather than multiple experimental treatments. In this report, both frequentist and Baysian adaptive designs were compared in terms of statistical power by a simulation study, assuming the situation when multiple experimental treatments are tested in multiple stages. The designs included in the current study are group sequential design (frequentist), adaptive design based on combination tests (frequentist), and Bayesian adaptive design (Bayesian). Based upon the results under multiple scenarios, the Bayesian adaptive design showed the highest power, and the design based on combination tests performed better than group sequential designs when proper interim adaptation could be conducted to increase power. / text

In the fast-paced technological revolution, technology has formed itself differently to facilitate the way to users to get their needs. As a matter of fact, people nowadays rely to a great extent on the smart devices as one of the essential creations of technology. They tend to access any website or web-application(s) through these devices fast and easily. Thus, paying enough attention to the design of any website or web-application is a major issue. This thesis project discusses the Responsive and Adaptive Design Methods as two important methods in terms of Websites and Web-Design. The methods have been theoretically discussed and explained to present the essential differences between them. Moreover, MyMusiC website has been implemented to show the differences between these methods practically. The prominent difference between the Responsive and Adaptive de-signs of the website makes it easy for the users to figure out the difference between the two design methods in terms of accessibility and ease of navigation. The results showed that the Responsive design is more user-friendly and more preferred by the users than the Adaptive design, as the users tend to use their smart devices first when they want to access a website than the computers.

In recent years, adaptive designs in clinical trials have been attractive due to their efficiency and flexibility. Response adaptive randomization procedures in phase II or III clinical trials are proposed to appeal ethical concerns by skewing the probability of patient assignments based on the responses obtained thus far, so that more patients will be assigned to a superior treatment group. General response-adaptive randomizations usually assume that the primary endpoint can be obtained quickly after the treatment. However, in real clinical trials, the primary outcome is delayed, making it unusable for adaptation. Therefore, we utilize surrogate and primary endpoints simultaneously to adaptively assign subjects between treatment groups for clinical trials with continuous responses. We explore two types of primary endpoints commonly used in clinical tirials: normally distributed outcome and time-to-event outcome. We establish a connection between the surrogate and primary endpoints through a Bayesian model, and then update the allocation ratio based on the accumulated data. Through simulation studies, we find that our proposed response adaptive randomization is more effective in assigning patients to better treatments as compared with equal allocation randomization and standard response adaptive randomization which is solely based on the primary endpoint.

Multiplicity issues arise prevalently in a variety of situations in clinical trials and statistical methods for multiple testing have gradually gained importance with the increasing number of complex clinical trial designs. In general, two types of multiple testing can be performed (Dmitrienko et al., 2009): union-intersection testing (UIT) and intersection-union testing (IUT). The UIT is of the interest in this dissertation. Thus, the familywise error rate (FWER) is required to be controlled in the strong sense. A number of methods have been developed for controlling the FWER, including single-step and stepwise procedures. In single-step approaches, such as the simple Bonferroni method, the rejection decision of a hypothesis does not depend on the decision of any other hypotheses. Single-step approaches can be improved in terms of power through stepwise approaches, while also controlling for the desired error rate. Besides, it is also possible to improve those procedures by a parametric approach. In the first project, we developed a new and powerful single-step progressive parametric multiple (SPPM) testing procedure for correlated normal test statistics. Through simulation studies, we demonstrate that SPPM improves power substantially when the correlation is moderate and/or the magnitude of eect sizes are similar. Group sequential designs (GSD) are clinical trials allowing interim looks with the possibility of early terminations due to ecacy, harm or futility, which can reduce the overall costs and timelines for the development of a new drug. However, repeated looks of data also have multiplicity issues and could inflate the type I error rate. The proper treatments to the error inflation have been discussed widely (Pocock, 1977), (O'Brien and Fleming, 1979), (Wang and Tsiatis, 1987), (Lan and DeMets, 1983). Most literature about GSD focuses on a single endpoint. GSD with multiple endpoints however, has also received considerable attention. The main focus of our second project is a GSD with multiple primary endpoints, in which the trial is to evaluate whether at least one of the endpoints is statistically signicant. In this study design, multiplicity issues arise from repeated interims and multiple endpoints. Therefore, the appropriate adjustments must be made to control the Type I error rate. Our second purpose here is to show that the combination of multiple endpoint and repeated interim analyses can lead to a more powerful design. Via the multivariate normal distribution, a method that allows for simultaneously consideration of interim analyses and all clinical endpoints was proposed. The new approach is derived from the closure principle, thus it can control type I error rate strongly. We evaluate the power under dierent scenarios and show that it compares favorably to other methods when correlation among endpoints is non-zero. In the group sequential design framework, another interesting topic is multiple arm multiple stage design (MAMS), where multiple arms are involved in the trial at the beginning with the flexibility about treatment selection or stopping decisions during the interim analyses. One of major hurdles of MAMS is the computational cost with the increasing number of arms and interim looks. Various designs were implemented to overcome this diculty (Thall et al., 1988; Schaid et al., 1990; Follmann et al., 1994; Stallard and Todd, 2003; Stallard and Friede, 2008; Magirr et al., 2012; Wason et al., 2017), but also control the FWER with the potential inflation from the multiple arm comparisons and multiple interim tests. Here, we consider a more flexible drop-the-loser design allowing the safety information in the treatment selection without a pre-specied dropping-arms mechanism and it still retains reasonable high power. The two dierent types of stopping boundaries are proposed for such a design. A sample size is also adjustable if the winner arm is dropped due to the safety considerations.

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[ES] Esta investigación tiene como objeto de estudio el diseño de estrategias pedagógicas para el diseño biomimético especulativo, sumándose a las alianzas transdisciplinarias de conocimiento que se están efectuando a nivel global entre la ciencia, el arte y el diseño. Estas estrategias académicas han sido diseñadas con la visión de adaptarse a este momento transicional de la sociedad en la era del del antropoceno. A lo largo de la investigación se reflexiona ante el reto que tenemos los profesores como formadores de diseñadores, y si al desarrollar una serie de estrategias pedagógicas que estimulen los procesos cognitivos a través de herramientas transdisciplinarias, permitiendo estimular el aprendizaje y el asombro hacia la tecnología análoga de la naturaleza, e impulsar las propuestas de diseño por medio de la visión del diseño especulativo, se lograría guiar al estudiante en su proceso creativo, para dar respuestas de diseño acordes al contexto actual transicional de la sociedad, rompiendo las barreras del pragmatismo. Se pretende también alimentar la investigación en torno a las estrategias de pedagogía del diseño biomimético especulativo, permitiendo sumar al cúmulo de didácticas disponibles para los académicos y todas las personas encargadas de la entrega del conocimiento. Se plantean como preguntas de investigación: ¿los estudiantes serán capaces de hacer la transferencia del conocimiento aprendido de organismos naturales para dar respuesta a un reto de diseño?, ¿qué herramientas pedagógicas se necesitan para lograrlo?, ¿a través de qué mecanismos sería posible sensibilizar a los estudiantes de su rol?, ¿por medio de qué estrategias didácticas se podría estimular la curiosidad de los estudiantes hacia el mundo natural como mecanismo de entendimiento y aprendizaje?, ¿a través de qué enfoques se podría potencializar al diseño como herramienta para dar respuestas a los retos actuales y del futuro?, ¿por medio de qué herramientas pedagógicas se puede lograr que los estudiantes se posicionen para desarrollar propuestas de diseño de valor? Para dar respuesta a ellas se han definido tres principios básicos que permiten plantear un trayecto para alcanzar el objetivo y a la vez forman la filosofía de enseñanza: a) la multidisciplina e interdisciplina, b) el enfoque biocéntrico y c) el diseño especulativo. Se realiza una investigación-acción enfocada en casos de estudio dentro del ámbito de la Universidad de Monterrey, en México, y es desarrollada en tres fases. En cada fase se diseña y se ponen a prueba durante 5 años una serie de estrategias pedagógicas, que se van alimentando a sí mismas para establecer el rediseño del siguiente modelo, generando 3 modelos, para finalmente plantear como resultado de la investigación una serie de estrategias pedagógicas finales (Modelo final). Para la validación de la información y de los resultados se ha utilizadola heurística, el sistema cruzado entre los datos recogidos por diversos mecanismos durante el desarrollo e implementación de las estrategias y, posteriormente, por medio de la evaluación realizada por expertos de los resultados proyectuales y la observación persistente de la autora de esta investigación. Los resultados obtenidos reflejan una evolución consecuente según se realiza el diseño y replanteo de los modelos 1, 2 y 3, estableciéndose que cada modelo va demostrando resoluciones cada vez más cercanas a los parámetros deseables de los resultados proyectuales. Se confía en haber contribuido a la investigación académica para la pedagogía con enfoque en sustentabilidad, en particular para el diseño biomimético y en la resolución de futuros. / [CA] Aquesta investigació té com a objecte d'estudi el disseny d'estratègies pedagògiques per al disseny biomimètic especulatiu, afegint-se a les aliances transdisciplinàries de coneixement que s'estan efectuant a nivell global entre la ciència, l'art i el disseny. Aquestes estratègies acadèmiques han estat dissenyades amb la visió d'adaptar-se a aquest moment transicional de la societat a l'era del de l'antropocè. Al llarg de la investigació es reflexiona davant el repte que tenim els professors com a formadors de dissenyadors, i si en desenvolupar una sèrie d'estratègies pedagògiques que estimulin els processos cognitius a través d'eines transdiscplinàries, permetent estimular l'aprenentatge i la sorpresa cap a la tecnologia anàloga de la natura, i impulsar les propostes de disseny per mitjà de la visió del disseny especulatiu, s'aconseguiria guiar l'estudiant en el procés creatiu, per donar respostes de disseny d'acord amb el context actual transicional de la societat, trencant les barreres del pragmatisme. Es pretén també alimentar la investigació al voltant de les estratègies de pedagogia del disseny biomimètic especulatiu, permetent sumar al cúmul de didàctiques disponibles per als acadèmics i totes les persones encarregades del lliurament del coneixement. Es plantegen com a preguntes de recerca: els estudiants seran capaços de fer la transferència del coneixement après d'organismes naturals per donar resposta a un repte de disseny?, quines eines pedagògiques es necessiten per aconseguir-ho?, a través de quins mecanismes seria possible sensibilitzar els estudiants del seu rol?, per mitjà de quines estratègies didàctiques es podria estimular la curiositat dels estudiants cap al món natural com a mecanisme d'enteniment i aprenentatge?, a través de quins enfocaments es podria potencialitzar al disseny com a eina per donar respostes als reptes actuals i del futur? Per mitjà de quines eines pedagògiques es pot aconseguir que els estudiants es posicionin per desenvolupar propostes de disseny de valor? Per donar-hi resposta s'han definit tres principis bàsics que permeten plantejar un trajecte per assolir l'objectiu i alhora formen la filosofia d'ensenyament: a) la multidisciplina i interdisciplina, b) l'enfocament biocèntric i c) el disseny especulatiu. Es realitza una investigació-acció enfocada en casos d'estudi dins l'àmbit de la Universitat de Monterrey, a Mèxic, i es desenvolupa en tres fases. A cada fase es dissenya i es posen a prova durant 5 anys una sèrie d'estratègies pedagògiques, que es van alimentant a si mateixes per establir el redisseny del model següent, generant 3 models, per finalment plantejar com a resultat de la investigació una sèrie d'estratègies pedagògiques finals (Model final). Per a la validació de la informació i dels resultats s'ha utilitzat l'heurística, el sistema creuat entre les dades recollides per diversos mecanismes durant el desenvolupament i la implementació de les estratègies i, posteriorment, per mitjà de l'avaluació realitzada per experts dels resultats projectuals i l'observació persistent de l'autora d'aquesta investigació. Els resultats obtinguts reflecteixen una evolució conseqüent segons es realitza el disseny i replanteig dels models 1, 2 i 3, establint-se que cada model va demostrant resolucions cada cop més properes als paràmetres desitjables dels resultats projectuals. Es confia haver contribuït a la investigació acadèmica per a la pedagogia amb enfocament en sustentabilitat, en particular per al disseny biomimètic i en la resolució de futurs. / [EN] This research has as its object of study the design of pedagogical strategies for speculative biomimetic design, adding to the transdisciplinary knowledge alliances the Estrategias pedagógicas adaptativas:Un enfoque en el diseño biomimético especulativo.at are taking place globally between science, art and design. These academic strategies have been designed with the vision of adapting to this transitional moment of society in the era of the Anthropocene. Throughout the research, we reflect on the challenge that teachers have as trainers of designers, and if by developing a series of pedagogical strategies that stimulate cognitive processes through transdisciplinary tools, allowing to stimulate learning and wonder towards technology. analogous to nature, and promoting design proposals through the vision of speculative design, it would be possible to guide the student in his creative process, to give design responses in accordance with the current transitional context of society, breaking the barriers of pragmatism. It is also intended to feed the research around the pedagogy strategies of the speculative biomimetic design, allowing to add to the accumulation of didactics available for academics and all the people in charge of the delivery of knowledge. They are posed as research questions: will students be able to transfer the knowledge learned from natural organisms to respond to a design challenge? What pedagogical tools are needed to achieve it? Through what mechanisms would it be possible? Make students aware of their role? Through what didactic strategies could students' curiosity towards the natural world be stimulated as a mechanism for understanding and learning? Through what approaches could design be potentiated as a tool for Give answers to current and future challenges? By means of what pedagogical tools can students be positioned to develop value design proposals? In order to respond to them, three basic principles have been defined that allow us to propose a path to achieve the objective and at the same time form the teaching philosophy: a) multidiscipline and interdiscipline, b) the biocentric approach and c) speculative design. An action-research focused on case studies is carried out within the scope of the University of Monterrey, in Mexico, and is developed in three phases. In each phase, a series of pedagogical strategies are designed and tested for 5 years, which feed themselves to establish the redesign of the following model, generating 3 models, to finally propose a series of strategies as a result of the investigation. final pedagogical (Final Model). For the validation of the information and the results, heuristics have been used, the crossed system between the data collected by various mechanisms during the development and implementation of the strategies and, later, through the evaluation carried out by experts of the project results and the persistent observation of the author of this investigation. The results obtained reflect a consistent evolution as the design and reconsideration of models 1, 2 and 3 is carried out, establishing that each model demonstrates resolutions that are closer and closer to the desirable parameters of the project results. It is hoped to have contributed to academic research for pedagogy with a focus on sustainability, in particular for biomimetic design and futures resolution. / Chi Muñoz, K. (2023). Estrategias pedagógicas adaptativas. Un enfoque en el diseño biomimético especulativo [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/195435

This quantitative study assessed the association of the design methods used for early phase oncology studies (adaptive versus traditional) and the outcome of late stage clinical trials. Differences by cancer type and by drug classification were also assessed. The theoretical and conceptual frameworks used were the general systems theory and the design and evaluation of complex interventions, respectively. Units of analysis were individual oncology studies in the ClinicalTrials.gov database and Bayesian logistic modeling was applied on a random sample of 381 studies initiated after November 1999 to December 2016. When assessing study design and outcome, there were lower odds of a positive outcome when adaptive methods were used though this association was not statistically significant (OR [95% highest posterior density (HPD)]:0.66 [0.20, 1.21]). Among the different drug types, using adaptive compared to traditional methods was associated with significantly higher odds of a positive outcome for taxanes, OR: 2.75, 95% HPD: 1.01, 5.16) and other, OR: 3.23, 95% HPD: 1.58, 5.46) but no association among studies of monoclonal antibodies or protein kinase inhibitors. Also, there were no significant associations between early phase study design and outcome in late phase studies by cancer type (lung, breast, other). Further research should be conducted using all completed oncology clinical trials in the database to more precisely determine the relationship between adaptive study design in early phase oncology studies and outcomes in late stage studies. Social change can occur through increased uptake of adaptive design methods, which may lead to more efficacious cancer treatment options.

The pharmaceutical industry now recognises the importance of the newly defined discipline of pharmacometrics. Pharmacometrics uses mathematical models to describe and then predict the performance of new drugs in clinical development. To ensure these models are useful, the clinical studies need to be designed such that the data generated allows the model predictions to be sufficiently accurate and precise. The capability of the available software to reliably estimate the model parameters must also be well understood.  This thesis investigated two important areas in pharmacometrics: optimal design and software estimation performance. The three optimal design papers progressed significant areas of optimal design research, especially relevant to phase II dose response designs. The use of exposure, rather than dose, was investigated within an optimal design framework. In addition to using both optimal design and clinical trial simulation, this work employed a wide range of metrics for assessing design performance, and was illustrative of how optimal designs for exposure response models may yield dose selections quite different to those based on standard dose response models. The investigation of the optimal designs for Poisson dose response models demonstrated a novel mathematical approach to the necessary matrix calculations for non-linear mixed effects models. Finally, the enormous potential of using optimal adaptive designs over fixed optimal designs was demonstrated. The results showed how the adaptive designs were robust to initial parameter misspecification, with the capability to "learn" the true dose response using the accruing subject data. The two estimation performance papers investigated the relative performance of a number of different algorithms and software programs for two complex pharmacometric models. In conclusion these papers, in combination, cover a wide spectrum of study designs for non-linear dose/exposure response models, covering: normal/non-normal data, fixed/mixed effect models, single/multiple design criteria metrics, optimal design/clinical trial simulation, and adaptive/fixed designs.