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A cost-benefit forecasting framework for assessment of advanced manufacturing technology developmentJones, Mark Benjamin 05 1900 (has links)
Development of new Advanced Manufacturing Technology (AMT) for the aerospace industry is critical to
enhance the manufacture and assembly of aerospace products. These novel AMTs require high development
cost, specialist resource capabilities, have long development periods, high technological risks and lengthy
payback durations. This forms an industry reluctance to fund the initial AMT development stages, impacting on
their success within an ever increasingly competitive environment.
Selection of suitable AMTs for development is typically performed by managers who make little reference to
estimating the non-recurring development effort in resources and hardware cost. In addition, the performance at
the conceptual stage is predicted using expert opinion, consisting of subjective and inaccurate outputs. AMTs
selected are then submerged into development research and heavily invested in, with incorrect selections having
a detrimental impact on the business.
A detailed study of the UK aerospace manufacturing industry corroborated these findings and revealed a
requirement for a new process map to resolve the problem of managing AMT developments at the conceptual
stages. This process map defined the final research protocol, forming the requirement for a Cost-Benefit
Forecasting Framework. The framework improves the decision making process to select the most suitable
AMTs for development, from concept to full scale demonstration. Cost is the first element and is capable of
estimating the AMT development effort in person-hours and cost of hardware using two parametric cost models.
Benefit is the second element and forecasts the AMT tangible and intangible performance. The framework plots
these quantified cost-benefit parameters and is capable of presenting development value advice for a diverse
range of AMTs with varied applications. A detailed case study is presented evaluating a total of 23 novel
aerospace AMTs verifying the capability and high accuracy of the framework within a large aerospace
manufacturing organisation. Further validation is provided by quantifying the responses from 10 AMT
development experts, after utilising the methodology within an industrial setting. The results show that
quantifying the cost-benefit parameters provides manufacturing research and technology with the ability to
select AMTs that provide the best value to a business.
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An analysis of technology support services for small and medium sized enterprises in selected industrial parks of Pretoria / Joseph MatjilaMatjila, Joseph January 2008 (has links)
Thesis (M.B.A.)--North-West University, Potchefstroom Campus, 2009.
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An analysis of technology support services for small and medium sized enterprises in selected industrial parks of Pretoria / Joseph MatjilaMatjila, Joseph January 2008 (has links)
Thesis (M.B.A.)--North-West University, Potchefstroom Campus, 2009.
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Technology acceptance in blended learning: The case of Jönköping International Business SchoolHuang, Wei, Paraschiv, Elena, Thuy, Dung Do January 2015 (has links)
Nowadays, in the new era of technology, everything needs to be updated, which represents a new challenge to education to adapt to the developments in technology. Moreover, due to the gap of theory separating practices in business schools, it is becoming obvious that the Universities can hardly help students to acquire experience. Due to this problem, business schools can limit the potential of students’ success. This study examines the efficiency of technology use in class as well as outside of the classroom. This was done by interviewing five teachers within different areas of teaching in Jönköping International Business School. The results show that there are many aspects that need to be considered such as policy, teacher development, the development of the virtual learning environment and other technological improvements, before applying technology in flipped classroom. / Den nya eran av teknik i dagens samhälle gör att allt måste uppdateras. Detta utgör en ny utmaning för utbildningen som bör anpassa sig till denna tekniska utveckling. Dessutom, som en följd av det teoretiska gapet som separeras från praxis i handelshögskolor är det tydligt att universiteten knappast kan hjälpa studenter att skaffa sig underförstådd kunskap. På grund av det här problemet kan handelshögskolor begränsa potentialen av studentens framgång. Däremot visar vår forskning att användningen av tekniken i det flippade klassrummet kan bidra till att förbättra situationen. Denna studie undersöker effektiviteten i teknikanvändning i klassrummet såväl som utanför klassrummet genom att intervjua fem lärare inom olika områden av undervisning på Jönköping Internationella Handels Högskola. Resultaten visar att det är många aspekter som bör beaktas, såsom policy, utvecklingsarbete av lärare, utveckling av VLE i tillägg till andra tekniska förbättringar, innan man applicerar tekniken i det flippade klassrummet.
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O papel dos institutos públicos de pesquisa no desenvolvimento tecnológico e na cooperação universidade-empresa. / The role of public research institutes in technology development and in university-industry cooperation.Luciana Oliveira Telles 15 December 2011 (has links)
Este trabalho investiga os projetos cooperativos de pesquisa coordenados por institutos públicos de pesquisa tecnológica (IPPs), com a participação de universidades, empresas e outros agentes do sistema de inovação. Considera-se que estas iniciativas possam ser um mecanismo para promover e acelerar a produção de inovações tecnológicas avançadas, tanto por permitir a reunião de diferentes e complementares capacitações, como por possibilitar a alavancagem de recursos financeiros. Nestes projetos, os IPPs têm aproveitado sua experiência em atividades nas fases intermediárias do processo de inovação para assumir o desafio de reunir os conhecimentos das ciências básicas e aplicadas, produzidos nas universidades, às suas capacitações tecnológicas, e aos conhecimentos das firmas sobre a produção e os seus negócios, com o objetivo de oferecer novas tecnologias para o mercado. Este trabalho também realiza um levantamento sobre as características dos IPPs e as formas como estas instituições têm se relacionado com as universidades e empresas. Para uma análise mais aprofundada destas experiências, foram selecionados três casos para a pesquisa de campo: o Fraunhofer Innovation Clusters, programa coordenado pelos Institutos Fraunhofer, na Alemanha, que apoia o desenvolvimento de projetos cooperativos entre agentes pertencentes a uma mesma região; o National Flagship Program, coordenado pela Commonwealth Scientific and Industrial Research Organisation (CSIRO), na Austrália; e por fim, os projetos Mobile Harbour e Online Electric Vehicle (OLEV), coordenados pelo Korea Advanced Institute of Science and Technology (KAIST), na Coreia do Sul. A decisão de apresentar a experiência do KAIST, apesar da instituição ser uma universidade, deve-se ao fato de esta ser enriquecedora para os propósitos deste trabalho. Os casos estudados indicaram o elevado investimento público destas iniciativas. As equipes destas instituições também mostraram que a qualidade das pesquisas é o ponto de partida para que as empresas queiram cooperar com os IPPs. Em seguida, os pesquisadores apontaram a relevância da capacidade de gestão dos projetos pelas equipes dos IPPs. Os casos apresentados tornaram evidente que gerar inovação pressupõe a capacidade de administrar os diversos assuntos que poderão afetar a adoção das tecnologias e que as empresas podem contribuir nestes processos. As experiências indicaram também que as universidades têm participado nos projetos, solucionando problemas científicos que impedem o desenvolvimento das tecnologias. Os resultados mostram que estas iniciativas têm contribuído para a produção de inovação para seus países. / This thesis investigates cooperative research coordinated by public research institutes (PRIs), with participation of universities, companies and other agents of the innovation system. It is considered that these initiatives may be a mechanism to promote and accelerate the development of advanced technological innovations, both by allowing the gathering of different and complementary capabilities, such as by allowing the leveraging of financial resources. In order to develop these projects, PRIs are assuming the challenge of joining the university basic and applied knowledge with their technological capabilities and the firms product development knowledge to propose high market value technologies. It is also identified some PRI characteristics and the ways these institutions have been working with universities and companies. For a more detailed analysis of their experiences, three cases were selected for field research: the Fraunhofer Innovation Clusters, a program coordinated by the Fraunhofer Institutes in Germany, which supports the development of cooperative projects between agents belonging to the same regions; the National Flagship Program, coordinated by the Commonwealth Scientific and Industrial Research Organisation (CSIRO), in Australia; and finally, the Mobile Harbour and Online Electric Vehicle (OLEV) projects, coordinated by the Korea Advanced Institute of Science and Technology (KAIST), in South Korea. The intention of presenting the KAIST experience is due to the fact that this may contribute to the purposes of this study, although it is a university. Cases studied indicated the high level of public investment in these initiatives. These institutions have also pointed the research quality as the starting point for cooperation with industry. Then, it was emphasised the ability of PRI members in project management. Experiences clarified that producing innovation requires the ability of managing various issues that may affect the adoption of technologies. It was also pointed that companies can contribute to these processes. These cases also showed that universities are participating by solving scientific problems that hinder the technology development. Conclusions are that these PRI initiatives are managing to contribute to produce relevant innovation to their countries.
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Idea Management in Technology Development : Evaluation Criteria for Value Proposition, Technology and StrategyDunstheimer, Markus January 2019 (has links)
Purpose Idea Management as key activity in the front-end of innovation is crucial for not only targeting new products but also for new technologies. Nevertheless, the interrelations between Idea Management and Technology Development are still not fully understood. Due to the different abstraction levels of products and technologies, an in-depth investigation of evaluation criteria for Technology Development ideas is required. Therefore, the purpose of this thesis is to examine which evaluation criteria are pertinent for each phase of Idea Management, when applied for Technology Development. Design The research framework for Idea Management criteria in the context of Technology Development is built on data from 17 semi-structured interviews, two focus group interviews as well as participant observations. The participants of this study are experienced R&D experts from a large Swedish organization in the transport industry. Findings The results indicate that the evaluation of Technology Development ideas is more complex due to the high degree of uncertainty and unpredictability. In contrast to the common one-step evaluation process of New Product Development ideas, the findings suggest a three-step evaluation process for Technology Development ideas. Due to the lack of knowledge and maturity when an idea is generated, this three-step evaluation enables a continuous reduction of uncertainty. In addition to this, the result of this study contributes with the suggestion to attribute a focus dimension for each Idea Management phase, which in consequence is helping firms to direct their evaluation resources. The findings are presented in a generic evaluation framework that leads organizations through the assessment process. Theoretical contribution The present study contributes to the literature with an improved understanding of TD idea evaluations by suggesting a rather internally use-oriented perspective as well as advances prior research through knowledge about the right timing for the use of evaluation criteria. Practical implications Irrespectively of the origin or focus of an idea, evaluation criteria are helping to direct Technology Development initiatives. By having evaluation criteria, defined as pertinent for each phase of Idea Management, Technology Development ideas can be assessed appropriately regarding their contextual circumstances. Originality The study is among the first that differentiates Idea Management for Technology Development from the one targeting New Product Development. This study suggests a framework that considers the stages and criteria necessary in the context of TechnologyDevelopment.
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The Development, Validation and Implementation of a Broad-Based ADME Genotyping Assay into Research and Clinical TrialsBrown, Andrew M.K. 12 1900 (has links)
Afin d’adresser la variabilité interindividuelle observée dans la réponse pharmacocinétique à de nombreux médicaments, nous avons créé un panel de génotypage personnalisée en utilisant des méthodes de conception et d’élaboration d’essais uniques. Celles-ci ont pour but premier de capturer les variations génétiques présentent dans les gènes clés impliqués dans les processus d'absorption, de distribution, de métabolisme et d’excrétion (ADME) de nombreux agents thérapeutiques. Bien que ces gènes et voies de signalement sont impliqués dans plusieurs mécanismes pharmacocinétiques qui sont bien connues, il y a eu jusqu’à présent peu d'efforts envers l’évaluation simultanée d’un grand nombre de ces gènes moyennant un seul outil expérimental. La recherche pharmacogénomique peut être réalisée en utilisant deux approches: 1) les marqueurs fonctionnels peuvent être utilisés pour présélectionner ou stratifier les populations de patients en se basant sur des états métaboliques connus; 2) les marqueurs Tag peuvent être utilisés pour découvrir de nouvelles corrélations génotype-phénotype. Présentement, il existe un besoin pour un outil de recherche qui englobe un grand nombre de gènes ADME et variantes et dont le contenu est applicable à ces deux modèles d'étude. Dans le cadre de cette thèse, nous avons développé un panel d’essais de génotypage de 3,000 marqueurs génétiques ADME qui peuvent satisfaire ce besoin. Dans le cadre de ce projet, les gènes et marqueurs associés avec la famille ADME ont été sélectionnés en collaboration avec plusieurs groupes du milieu universitaire et de l'industrie pharmaceutique. Pendant trois phases de développement de cet essai de génotypage, le taux de conversion pour 3,000 marqueurs a été amélioré de 83% à 97,4% grâce à l'incorporation de nouvelles stratégies ayant pour but de surmonter les zones d'interférence génomiques comprenant entre autres les régions homologues et les polymorphismes sous-jacent les régions d’intérêt. La précision du panel de génotypage a été validée par l’évaluation de plus de 200 échantillons pour lesquelles les génotypes sont connus pour lesquels nous avons obtenu une concordance > 98%. De plus, une comparaison croisée entre nos données provenant de cet essai et des données obtenues par différentes plateformes technologiques déjà disponibles sur le marché a révélé une concordance globale de > 99,5%. L'efficacité de notre stratégie de conception ont été démontrées par l'utilisation réussie de cet essai dans le cadre de plusieurs projets de recherche où plus de 1,000 échantillons ont été testés. Nous avons entre autre évalué avec succès 150 échantillons hépatiques qui ont été largement caractérisés pour plusieurs phénotypes. Dans ces échantillons, nous avons pu valider 13 gènes ADME avec cis-eQTL précédemment rapportés et de découvrir et de 13 autres gènes ADME avec cis eQTLs qui n'avaient pas été observés en utilisant des méthodes standard. Enfin, à l'appui de ce travail, un outil logiciel a été développé, Opitimus Primer, pour aider pour aider au développement du test. Le logiciel a également été utilisé pour aider à l'enrichissement de cibles génomiques pour d'expériences séquençage. Le contenu ainsi que la conception, l’optimisation et la validation de notre panel le distingue largement de l’ensemble des essais commerciaux couramment disponibles sur le marché qui comprennent soit des marqueurs fonctionnels pour seulement un petit nombre de gènes, ou alors n’offre pas une couverture adéquate pour les gènes connus d’ADME. Nous pouvons ainsi conclure que l’essai que nous avons développé est et continuera certainement d’être un outil d’une grande utilité pour les futures études et essais cliniques dans le domaine de la pharmacocinétique, qui bénéficieraient de l'évaluation d'une longue liste complète de gènes d’ADME. / In order to better assess the inter-individual variability observed in a patient’s pharmacokinetic response to many medications, we have created a custom genotyping panel that uses unique assay designs to analyze variation present in key genes involved in the absorption, distribution, metabolism and excretion (ADME) of many therapeutic agents. These genes and pathways involved in most pharmacokinetic mechanisms are well known. However, as yet, there has been little effort to develop tools that can interrogate a large number of variations in most known drug metabolizing genes simultaneously within a single experimental tool. Pharmacogenomic research has historically been conducted using two approaches: targeted studies that screen a small number of specific functional markers to identify known metabolic status phenotypes, and genome-wide studies that identify novel genetic correlations with drug response phenotypes. Thus, a gap currently exists for a targeted ADME research tool that can evaluate a large number of key ADME genes and variants in a format that can be applicable to both types of study designs. As part of this thesis, we have developed a 3000 SNP broad based ADME genotyping panel that can address this need.
Genes and markers for the genotyping panel were selected in collaboration with many groups from both academia and the pharmaceutical industry in an effort to capture all pertinent genes and metabolic pathways that have been implicated in drug metabolism. The final assay design was composed of over 3000 markers in 181 genes. Over three phases of iterative development, the assay conversion rate for the 3000 markers was improved from 83.0% to 97.4% through the incorporation of novel design strategies to overcome areas of genomic interference such as regions of homology and underlying polymorphisms. Accuracy of the assay was validated by screening more than 200 samples of known genotype with a concordance of 99%. Additionally, data from the assay has also been compared to data from different technological platforms and has an overall concordance of 99.5%. The effectiveness of the design strategy was demonstrated in the successful utilization of the assay in the screening of over 1000 samples which identified several novel pharmacogenetic associations between ADME variations and adverse drug reactions in children. Another goal of this thesis was to demonstrate what added benefit/utility the 3000 SNP ADME panel would have when compared to currently available genotyping assays. Using 150 extensively investigated liver samples, the broad based assay was not only able to detect and validate 13 previously reported cis eQTLs in ADME genes but further identified an additional 13 novel ADME cis eQTLs that had never been observed before, doubling the number previously identified using standard methods on the same samples. Finally, in support of this work, a number of bioinformatic tools had to be developed to help expedite this research. These tools have been further refined and are currently being used to assist with enrichment of genomic targets for next generation sequencing experiments.
In conclusion, this work has led to a better understanding of ADME genetics and the nuances of assaying ADME genes. The content and designs of the developed assay sets it apart from currently available commercial assays that contain only functional markers in a small number of genes or do not have adequate coverage across ADME genes. The assay has the ability to play a significant role in pharmacogenomic studies to identify known and novel pharmacogenomic biomarkers. These will lead to improved biomarkers that will help better stratify pharmaceutical clinical trial populations or assist physicians to select better, more personalized, efficacious and safer therapies for their patients.
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Skipping a generation of weapons system technology : the impact on the Department of Defense and the defense industrial baseAtkinson, Thomas A. 03 1900 (has links)
During the 2000 presidential race, then Texas Governor George W. Bush advocated transforming and reforming how the Department of Defense (DoD) acquires new weapon systems. He promised a "revolution" that would "skip a generation of technology," in order to "move on to futuristic weapons without necessarily buying all those in development." This thesis examines President Bush's proposal and analyzes the potential impact on DoD and the defense industry. Ultimately the research revealed that there are ways to improve the acquisition process and protect the defense industry. The primary conclusion of the research is that it is feasible to skip current weapon systems in development, in order to begin research and development of the next-generation weapon systems. However, DoD will be impacted through higher operations and sustainment (O & S) costs to sustain existing weapon systems if weapon systems currently in development are skipped. The acquisition professionals that participated in this study believe these O & S costs could increase up to 10% per year for anywhere from five to 20 years depending on the type of system. This thesis makes additional recommendations and areas of further research. / Captain, United States Marine Corps
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The Policy Evaluation Structure for Government Subsidies on Small and Medium Enterprises Innovation ProgramLee, Feng-wu 08 September 2010 (has links)
Government support for applied Research and Development (R&D) persisted in
the US despite evidence to the contrary. Many provide government R&D funding for
enterprises of particular interest and a number of countries have substantially
increased their expenditure on R&D. SBIR as a means of funding high-risk R&D
with broad commercial and societal benefits that would not be undertaken by a single
company, either because the risk was too high or because a large enough share of the
benefits of success would not accrue to the company for it to make the investment.
Therefore, the program¡¦s goal is to the development and application of new, enabling
technologies that individual firms would not or pursue on their own and thereby
encourage the economic growth that comes from the commercialization and use of
new technologies in the private sector. However, very few studies of R&D policy
toward innovative subsidy program in developing country. Public programs to
subsidize high-technology firms have represented a significant but little-studied area
of public expenditures. This article assesses the long-run success of firms
participating in the SBIR program in Taiwan. The plan of this research is as follows.
The purpose of this search in Taiwan is to study the impact of
government-industry R&D programs on private R&D. The research has 3 important
aspects. First, using a questionnaire to understand the enterprises intention and
behavior which have participated in the ¡§Small Business Innovation Research
(SBIR)¡¨ this paper first examines whether government R&D subsidies influence
firm¡¦s innovative activities. Second, this paper examines what the correlation is
between government funding and private R&D expenditures. Finally, this research
conducted 67 important interviews from enterprises. Not only the multi-methodology
comparisons, the empirical results aimed at:
1) Examine the role of public/private partnerships (PP/Ps) as an instrument to
leverage public investment in strategy technology and innovation and to achieve
other goals of technology and innovation policy;
2) Identify the critical factors determining the success of R&D subsidy program for
innovation, with an emphasis on programme design, financial arrangement, and
evaluation
3) Government R&D subsidies have a significant positive effect or not on firm¡¦s R&D
expenditure / employment / firm-financed R&D spending.
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The Development, Validation and Implementation of a Broad-Based ADME Genotyping Assay into Research and Clinical TrialsBrown, Andrew M.K. 12 1900 (has links)
Afin d’adresser la variabilité interindividuelle observée dans la réponse pharmacocinétique à de nombreux médicaments, nous avons créé un panel de génotypage personnalisée en utilisant des méthodes de conception et d’élaboration d’essais uniques. Celles-ci ont pour but premier de capturer les variations génétiques présentent dans les gènes clés impliqués dans les processus d'absorption, de distribution, de métabolisme et d’excrétion (ADME) de nombreux agents thérapeutiques. Bien que ces gènes et voies de signalement sont impliqués dans plusieurs mécanismes pharmacocinétiques qui sont bien connues, il y a eu jusqu’à présent peu d'efforts envers l’évaluation simultanée d’un grand nombre de ces gènes moyennant un seul outil expérimental. La recherche pharmacogénomique peut être réalisée en utilisant deux approches: 1) les marqueurs fonctionnels peuvent être utilisés pour présélectionner ou stratifier les populations de patients en se basant sur des états métaboliques connus; 2) les marqueurs Tag peuvent être utilisés pour découvrir de nouvelles corrélations génotype-phénotype. Présentement, il existe un besoin pour un outil de recherche qui englobe un grand nombre de gènes ADME et variantes et dont le contenu est applicable à ces deux modèles d'étude. Dans le cadre de cette thèse, nous avons développé un panel d’essais de génotypage de 3,000 marqueurs génétiques ADME qui peuvent satisfaire ce besoin. Dans le cadre de ce projet, les gènes et marqueurs associés avec la famille ADME ont été sélectionnés en collaboration avec plusieurs groupes du milieu universitaire et de l'industrie pharmaceutique. Pendant trois phases de développement de cet essai de génotypage, le taux de conversion pour 3,000 marqueurs a été amélioré de 83% à 97,4% grâce à l'incorporation de nouvelles stratégies ayant pour but de surmonter les zones d'interférence génomiques comprenant entre autres les régions homologues et les polymorphismes sous-jacent les régions d’intérêt. La précision du panel de génotypage a été validée par l’évaluation de plus de 200 échantillons pour lesquelles les génotypes sont connus pour lesquels nous avons obtenu une concordance > 98%. De plus, une comparaison croisée entre nos données provenant de cet essai et des données obtenues par différentes plateformes technologiques déjà disponibles sur le marché a révélé une concordance globale de > 99,5%. L'efficacité de notre stratégie de conception ont été démontrées par l'utilisation réussie de cet essai dans le cadre de plusieurs projets de recherche où plus de 1,000 échantillons ont été testés. Nous avons entre autre évalué avec succès 150 échantillons hépatiques qui ont été largement caractérisés pour plusieurs phénotypes. Dans ces échantillons, nous avons pu valider 13 gènes ADME avec cis-eQTL précédemment rapportés et de découvrir et de 13 autres gènes ADME avec cis eQTLs qui n'avaient pas été observés en utilisant des méthodes standard. Enfin, à l'appui de ce travail, un outil logiciel a été développé, Opitimus Primer, pour aider pour aider au développement du test. Le logiciel a également été utilisé pour aider à l'enrichissement de cibles génomiques pour d'expériences séquençage. Le contenu ainsi que la conception, l’optimisation et la validation de notre panel le distingue largement de l’ensemble des essais commerciaux couramment disponibles sur le marché qui comprennent soit des marqueurs fonctionnels pour seulement un petit nombre de gènes, ou alors n’offre pas une couverture adéquate pour les gènes connus d’ADME. Nous pouvons ainsi conclure que l’essai que nous avons développé est et continuera certainement d’être un outil d’une grande utilité pour les futures études et essais cliniques dans le domaine de la pharmacocinétique, qui bénéficieraient de l'évaluation d'une longue liste complète de gènes d’ADME. / In order to better assess the inter-individual variability observed in a patient’s pharmacokinetic response to many medications, we have created a custom genotyping panel that uses unique assay designs to analyze variation present in key genes involved in the absorption, distribution, metabolism and excretion (ADME) of many therapeutic agents. These genes and pathways involved in most pharmacokinetic mechanisms are well known. However, as yet, there has been little effort to develop tools that can interrogate a large number of variations in most known drug metabolizing genes simultaneously within a single experimental tool. Pharmacogenomic research has historically been conducted using two approaches: targeted studies that screen a small number of specific functional markers to identify known metabolic status phenotypes, and genome-wide studies that identify novel genetic correlations with drug response phenotypes. Thus, a gap currently exists for a targeted ADME research tool that can evaluate a large number of key ADME genes and variants in a format that can be applicable to both types of study designs. As part of this thesis, we have developed a 3000 SNP broad based ADME genotyping panel that can address this need.
Genes and markers for the genotyping panel were selected in collaboration with many groups from both academia and the pharmaceutical industry in an effort to capture all pertinent genes and metabolic pathways that have been implicated in drug metabolism. The final assay design was composed of over 3000 markers in 181 genes. Over three phases of iterative development, the assay conversion rate for the 3000 markers was improved from 83.0% to 97.4% through the incorporation of novel design strategies to overcome areas of genomic interference such as regions of homology and underlying polymorphisms. Accuracy of the assay was validated by screening more than 200 samples of known genotype with a concordance of 99%. Additionally, data from the assay has also been compared to data from different technological platforms and has an overall concordance of 99.5%. The effectiveness of the design strategy was demonstrated in the successful utilization of the assay in the screening of over 1000 samples which identified several novel pharmacogenetic associations between ADME variations and adverse drug reactions in children. Another goal of this thesis was to demonstrate what added benefit/utility the 3000 SNP ADME panel would have when compared to currently available genotyping assays. Using 150 extensively investigated liver samples, the broad based assay was not only able to detect and validate 13 previously reported cis eQTLs in ADME genes but further identified an additional 13 novel ADME cis eQTLs that had never been observed before, doubling the number previously identified using standard methods on the same samples. Finally, in support of this work, a number of bioinformatic tools had to be developed to help expedite this research. These tools have been further refined and are currently being used to assist with enrichment of genomic targets for next generation sequencing experiments.
In conclusion, this work has led to a better understanding of ADME genetics and the nuances of assaying ADME genes. The content and designs of the developed assay sets it apart from currently available commercial assays that contain only functional markers in a small number of genes or do not have adequate coverage across ADME genes. The assay has the ability to play a significant role in pharmacogenomic studies to identify known and novel pharmacogenomic biomarkers. These will lead to improved biomarkers that will help better stratify pharmaceutical clinical trial populations or assist physicians to select better, more personalized, efficacious and safer therapies for their patients.
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